AU2012201997A1 - Hydrazide compound and pesticidal use of the same - Google Patents

Abstract

A hydrazide compound represented by the formula (I): A' 4 NRl-C-J 6 C- NR2 -NR 3-Q (I) has excellent pesticidal activity. P/00/008b

Description

Australian Patents Act 1990 - Regulation 3.2A ORIGINAL COMPLETE SPECIFICATION STANDARD PATENT Invention Title "Hydrazide compound and pesticidal use of the same" The following statement is a full description of this invention, including the best method of performing it known to me/us: C\NRPortbl\DCC\JXTn4239052 ],DOC DESCRIPTION HYDRAZIDE COMPOUND AND PESTICIDAL USE OF THE SAME This is a divisional of Australian patent application No. 2006300182, the entire contents of which are incorporated herein by reference. Technical Field The present invention relates to a hydrazide compound and pesticidal use of the same. Background Art In WO 01/70671, WO 03/015518, WO 03/016284, WO 03/016300 and WO 03/024222, certain amide compounds are known to be compounds having pesticidal activity. Disclosure of the Invention The present invention advantageously provides a compound having excellent efficacy of controlling pests. The present inventors have intensively studied in order to find out a compound having excellent efficacy of controlling pests and, as a result, found out that a hydrazide compound represented by the following formula (1) has excellent controlling efficacy. According to the present invention, there is provided: (1) A hydrazide compound represented by the formula (1): -2 4NRi- ( 4 i 2 (1) 5 ' -N R 2

-NR

3 _Q 6 A 2 wherein Ri represents a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C2-C6 5 cyanoalkyl group, a C2-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, a C3-C6 alkynyl group optionally substituted with at least one halogen atom, or a C7-C9 phenyl alkyl group whose benzene ring 10 moiety may be substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one 15 halogen atom,

R

2 and R 3 independently represent a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 acyl group, a C2-C6 alkoxycarbonyl group, a C3-C7 N,N-dialkylcarbamoyl group, or a phenyl group optionally 20 substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group and (4) a Cl-C6 alkyl group optionally 3 substituted with at least one halogen atom,

R

4 represents a halogen atom, a cyano group, a nitro group, a C1-C6 alkyl group optionally substituted with.at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with 5 at least one halogen atom, a phenyl group optionally substituted with at least one halogen atom, a C1-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group 10 optionally substituted with at least one halogen atom, or two R4 groups which are bound to the adjacent carbon atoms are bound at their terminal ends to each other to form a group Tl or T2 Tl: -CR 41

=CR

42

-CR

43

=CR

44 T2: -(CR 45R4) 15 (wherein R 41 , R 42 , R 43 and R 44 independently, represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 alkoxy group optionally substituted with at least one halogen atom, a C1-C6 alkylthio group optionally substituted 20 with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, R45 and R independently represent a hydrogen atom, or a 25 Cl-C6 alkyl group optionally substituted with at least one halogen atom, and h represents an integer of 3 or 4), n represents an integer of 0 to 4 (provided that, when n is an integer of 2 or more, R 's may be the same or different), 5 Q represents a group selected from Q1 to Q6: Q1 -C(=A 31)-R5 Q2 -- C(=A 32 )-OR' Q3 -C(=A 3 3

)-SR

7 Q4 -- C(=A4)-NROR 9 Q5 -S(0) 2

-R

0 Q6 -S(0) 2 -NR R2 (wherein A , A 32, A and A34 represent an oxygen atom or a sulfur atom,

R

5 represents a hydrogen atom; a C2-C6 alkenyl group 10 optionally substituted with at least one halogen atom; a C2-C6 alkynyl group optionally substituted with at least one halogen atom; a Cl-C6 alkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a Cl-C6 alkoxy group, (3) 15 a Cl-C6 alkylthio group, (4) a Cl-C6 alkylsulfinyl group, (5) a Cl-C6 alkylsulfonyl group, (6) a C2-C6 dialkylamino group and (7) a C3-C6 cycloalkyl group; a C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a 20 halogen atom, (2) a Cl-C6 alkyl group; a phenyl group optionally substituted with 1 to 5 independent substituents selected from .5 the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, 5 (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally 10 substituted with at least one halogen atom and (10) a C2-C6 alkoxycarbonyl group optionally substituted with at least one halogen atom; a naphthyl group optionally substituted with 1 to 9 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro 15 group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; a 5- to 6-membered heteroaryl group optionally substituted with one or more independent substituents selected from the group consisting of 20 (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; a 3- to 8-membered non-aromatic heterocyclic group optionally substituted with 25 one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group; a C7-C9 phenylalkyl group whose benzene ring moiety may be substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, 5 (3) a nitro group, (4)1a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a C1-C6 alkoxy group optionally substituted with at least one halogen atom; or a C7-C9 phenoxyalkyl group whose benzene ring moiety may be substituted with 1 to 5 independent substituents 10 selected from the group consisting of (1) a halogen atom, (2) a cya,no group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, 15 R 6 and R 7 represent a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a C3-C6 alkoxyalkyl group optionally substituted 'with at least one halogen atom; a C2-C6 alkenyl group optionally substituted with at least one halogen atom; a C3-C6 alkynyl group optionally substituted with 20 at least one halogen atom; a C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group; a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting 25 of (1) a halogen atom, (2) a cyano group, (3) a nitro group, .7 (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a C1-C6 alkoxy group optionally substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one 5 halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, (8) a C1-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally substituted with at least one halogen atom and (10) a C2-C6 10 alkoxycarbonyl group optionally substituted with at least one halogen atom; a 5- to 6-membered heteroaryl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally 15 substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; or a C7-C9 phenylalkyl group whose benzene ring moiety may be substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) 20 a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a C1-C6 alkoxy group optionally substituted with at least one halogen atom, R8 and R 9 independently represent a hydrogen atom; a Cl-C6 25 alkyl group optionally substituted with at least one halogen 8 atom; a C2-C6 alkoxyalkyl group optionally substituted with at least one halogen atom; a C2-C6 alkenyl group optionally substituted with at least one halogen atom; a C3-C6 alkynyl group optionally substituted with at least one halogen atom; 5 a C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group; a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a 10 halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group, optionally substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 15 alkylsulfinyl group optionally substituted with at least one halogen atom, (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally substituted with at least one halogen atom and (10) a C2-C6 alkoxycarbonyl group optionally 20 substituted with at least one halogen atom; a 5- to 6-membered heteroaryl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen 25 atom and (5) a Cl-C6 alkoxy group optionally substituted with -9 at least one halogen atom; or a C7-C9 phenylalkyl group whose benzene ring moiety may be substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 5 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; or Re and R 9 are taken together with the nitrogen atom to which they are bound to form a 3- to 8-membered non-aromatic heterocyclic group, the 3- to 10 8-membered non-aromatic heterocyclic group may contain, in the ring,,one or more independent groups selected from the group consisting of (1) an oxygen atom, (2) a sulfur group and (3) a -NRa- group (wherein Ra represents a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C2-C6 15 alkoxycarbonyl group optionally substituted with at least one halogen atom, or a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at 20 least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom), and carbon atom(s) in the ring may be substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a Cl-C6 alkyl group optionally substituted 25 with at least one halogen atom and (3) a C2-C6 alkoxycarbonyl 10 group optionally substituted with at least one halogen atom, Rio represents a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a C3-C6 cycloalkyl group optionally substituted with one or more independent 5 substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group optionally substituted with at least one halogen atom; or a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, 10 (3) a nitro group, (4) a C1-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, and

R

1 1 and R1 2 independently represent a Cl-C6 alkyl group 15 optionally substituted with at least one halogen atom; a C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group optionally substituted with at least one halogen atom; or a phenyl group 20 optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one 25 halogen atom; or R" and R1 2 are taken together with the nitrogen -11 atom to which they are bound to form a 3- to 8-membered non-aromatic heterocyclic group, the 3- to 8-membered non-aromatic heterocyclic group may contain, in the ring, one or more independent groups selected from the group consisting 5 of (1) an oxygen atom, '(2) a sulfur atom and (3) a -NRb-group (wherein Rb represents a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C2-C6 alkoxycarbonyl group optionally substituted with at least one halogen atom, or a phenyl group optionally substituted with 1 10 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom), and carbon atom(s) 15 in the ring may be substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (3) a C2-C6 alkoxycarbonyl group optionally substituted with at least one halogen atom), 20 J represents a group represented by Jl or J2: ( R14a 1 b za fY a b bq 1 \\ a J2 R N Zb.O -- 3 413a (wherein Xa, ya, Za, Xb, yb and Zb independently represent CH or 12 a nitrogen atom, R1a and RG3 represent a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a C2-C6 cyanoalkyl group; a C2 7 C6 alkoxyalkyl group optionally substituted with 5 at least one halogen atom; a C2-C6 alkenyl group optionally substituted with at least one halogen atom; a C2-C6 alkynyl group optionally substituted with at least one halogen atom; a C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group 10 consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group; a phepyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen 15 atom, (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom and (8) a Cl-C6 alkylsulfonyl group optionally 20 substituted with at least one halogen atom; a 5- to 6-membered heteroaryl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at 25 least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; a C7-C9 phenylalkyl group whose benzene ring moiety may be substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; or a C7-C9 pyridinylalkyl group whose pyridine ring moiety may be substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, R1 4 a and R14b represent a halogen atom; a cyano group; a nitro group; an isocyanato group; a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a C1-C6 alkoxy group optionally substituted with at least one halogen atom; a C2-C6 cyanoalkyloxy group; a C3-C6 alkoxyalkyloxy group optionally substituted with at least one halogen atom; a C3-C6 alkenyloxy group optionally substituted with at least one halogen atom; a C3-C6 alkynyloxy group optionally substituted with at least one halogen atom; a Cl-C6 alkylthio group optionally substituted with at least one halogen atom; a C1-C6 alkylsulfinyl group optionally substituted with at least one 14 halogen atom; a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom; a phenyl group optionally substituted with 1 to 5 independent,substituents selected from the group consisting of (1) a halogen atom, (2)' 5 a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; a 5- to 6-membered heteroaryl group optionally substituted with one or more independent substituents selected 10 from the group consisting of (1) a halogen atom, (2) a cyano group,, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; or a phenoxy group optionally substituted with 1 to 5 15 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, 20 p represents an integer of 0 to 3, and q represents an integer of 0 to 3 (provided that, when p is an integer of 2 or 3, two or more R 1 4a's may be the same or different and, when q is an integer of 2 or 3, two or more R14b's may be the same or different), and 25 A' and A 2 independently represent an oxygen atom or a 15 sulfur atom (hereinafter referred to as the present compound). (2) The compound according to the above (1), wherein n is an integer of 0 to 3. (3) The compound according to the above (2), wherein R 4 ' 5 is a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 alkoxy group optionally substituted with at least one halogen atom, a phenyl group optionally substituted with at least one halogen atom, or two R 4 groups which are bound to the adjacent carbon atoms 10 are bound at their terminal ends to form a group Tl: -CR 4=CR 42-CR 43=CR 44 (wherein R 41 , R 42 , R43 and R 4 4 represent a hydrogen atom). (4) The compound according to the above (3), wherein R 4 is a fluorine atom, a chlorine atom, a bromine atom, an iodine 15 atom, a cyano group, a methyl group, an ethyl group, a trifluoromethyl group, a methoxy group, a phenyl group, or two R4 groups which are bound to the adjacent carbon atoms are bound 41 42 43= 44_ at their terminal ends to form a group Tl: -CR '=CR -CR =CR (wherein R 41 , R 4 2 , R 4 3 and R 4 4 represent a hydrogen atom). 20 (5) The compound according to any one of the above (1) to (4), wherein J is Jl, Ya is CH,

R

13 a is a Cl-C6 alkyl group optionally substituted with at 25 least one halogen atom; a C3-C6 cycloalkyl group optionally , 16 substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group; a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting 5 of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one 10 halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom and (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom; or a 5- to 6-membered heteroaryl group optionally substituted with one or more independent substituents selected 15 from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, 20 R1a is a halogen atom; a cyano group; a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a Cl-C6 alkylthio group optionally substituted with at least one halogen atom; a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom; a C1-C6 25 alkylsulfonyl group optionally substituted with at least one 17 halogen atom; or a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at 5 least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, and p is an integer of 0 to 2. (6) The compound according to any one of the above (1) to (4), wherein 10 J is J2, yb is CH, R13b is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R1 4 b is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a phenyl group optionally 15 substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen 20 atom, and q is 1. (7) The compound according to any one of the above (1) to (6), wherein A and A2 are an oxygen atom, and R1 is a hydrogen atom or a methyl group. 25 (8) The compound according to any one of the above (1) to -18 (7), wherein Q is Q1, A31 is an oxygen atom, and

R

5 is a hydrogen atom; a C1-C6 alkyl group optionally 5 substituted with one or'more independent substituents selected from the group consisting of (1) a halogen atom, (2) a Cl-C6 alkoxy group, (3) a C1-C6 alkylthio group, (4) a Cl-C6 alkylsulfinyl group, (5) a Cl-C6 alkylsulfonyl group, (6) a C2-C6 dialkylamino group and (7) a C3-C6 cycloalkyl group; a 10 C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen and (2) a Cl-C6 alkyl group; a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) 15 a cyano group, (3) a nitro group, (4) a C1-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, (6) a C1-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 20 alkylsulfinyl group optionally substituted with at least one halogen atom, (8) a C1-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally substituted with at least one halogen atom and (10) a C2-C6 alkoxycarbonyl group optionally 25 substituted with at least one halogen atom; a 5- to 6-membered -19 heteroaryl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one' 5 halogen atom and (5) a'Cl-C6 alkoxy group optionally substituted with at least on'e halogen atom; or a 3 to 8-membered non-aromatic heterocyclic group optionally substituted with one or more independent groups selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group. 10 (9) The compound according to the above (8), wherein R 5 is a hydrogen atom, a methyl group, an ethyl group, a tert-butyl group, a cyclopropyl group, a phenyl group, a 3-methylphenyl group, a 4-methoxyphenyl group, a 2-pyridinyl group, or a morpholino group. 15 (10) The compound according to any one of the above (1) to (7), wherein Q is Q2, A is an oxygen atom, and

R

6 is a Cl-C6 alkyl group optionally substituted with at 20 least one halogen atom; a C2-C6 alkenyl group optionally substituted with at least one halogen atom; or a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group 25 optionally substituted with at least one halogen atom, (5) a 20 Cl-C6 alkoxy group optionally substituted with at least *one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one 5 halogen atom, (8) a C1l'C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally substituted with at least one halogen atom and (10) a C2-C6 alkoxy carbonyl group optionally substituted with at least one halogen atom. 10 (11) The compound according to the above (10), wherein R 6 is a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, a sec-butyl group, a 2-propenyl group, or a phenyl group. (12) The compound according to any one of the above (1) 15 to (7), wherein Q is Q4,

A

34 is an oxygen atom, and Re and R 9 independently represent a hydrogen atom; a Cl-C6 alkyl group optionally substituted with at least one halogen 20 atom; or a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally subs-tituted 25 with at least one halogen atom, (6) a Cl-C6 alkylthio group .21 optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 5 dialkylamino group optionally substituted with at least one halogen atom and (10) a C2-C6 alkoxy carbonyl group optionally substituted 'with at least one halogen atom. (13) The compound according to the above (12), wherein Ra and R 9 , each, independently, represent a hydrogen atom, a 10 methyl group, an ethyl group, or a phenyl group. (14) The compound according to any one of the above (1) to (13), wherein R2 is a hydrogen atom or a methyl group, and

R

3 is a hydrogen atom, a methyl group, an isopropyl group, or a methoxycarbonyl group. 15 (15) The compound according to the above (1), wherein R1 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R2 is a hydrogen atom, or a C1-C6 alkyl group optionally substituted with at least one halogen atom, 20 R 3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group,

R

4 is a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 25 alkoxy group optionally substituted with at least one halogen 22 atom, or a phenyl group optionally substituted with at least one halogen atom, or two R 4 groups which are bound to the adjacent carbon atoms are bound at their terminal ends to form Tl: -CR =CR2-CR 43

=CR

44 5 (wherein R 41 , R 4 2 , R 4 3 and R 44 represent a hydrogen atom) , n is an integer of 0 to 3, Q is a group represented by Q1 to Q6: Q1 -- C(=A 3 1)-R 5 Q2 -C(=A 32 )-OR' Q3 -C(=Asa)-SR' Q4 -- C(=A34)-NROR' Q5 -S() 2 -Ro Q6 -S() 2 -NR"R1 2 (wherein A 3 1 , A 32 and A 33 are an oxygen atom, A 34 is an oxygen 10 atom or a sulfur atom,

R

5 is a hydrogen atom; a Cl-C6 alkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a C1-C6 alkoxy group, (3) a Cl-C6 alkylthio group, (4) a Cl-C6 15 alkylsulfinyl group, (5) a Cl-C6 alkylsulfonyl group, (6) a C2-C6 dialkylamino group and (7) a C3-C6 cycloalkyl group; a C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group; a phenyl group 20 optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) .23 a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally substituted withat least one halogen atom, (6) a Cl-C6 alkylthio group optionally 5 substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, (8) a C1-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally substituted with at least one 10 halogen atom and (10) a C2-C6 alkoxycarbonyl group optionally substituted with at least one halogen atom; a 5- to 6-membered heteroaryl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) 15 a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; or a 3- to 8-membered non-aromatic heterocyclic group optionally substituted with one or more independent substituents selected 20 from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group, R6 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a C2-C6 alkenyl group optionally substituted with at least one halogen atom; or a phenyl group 25 optionally substituted with 1 to 5 independent substituents ,24 selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally substituted with at least one' 5 halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 10 dialkylamino group optionally substituted with at least one halogen atom and (10) a C2-C6 alkoxycarbonyl group optionally substituted with at least one, halogen atom,

R

7 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 15 R 8 and R 9 independently represent a hydrogen atom; a Cl-C6 alkyl group optionally substituted with at least one halogen atom; or a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) 20 a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a C1-C6 alkoxy group optionally substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least 25 one halogen atom, (8) a Cl-C6 alkylsulfonyl group optionally ,25 substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally substituted with at least one halogen atom and (10) a C2-C6 alkoxycarbonyl group optionally substitutedwith at least one halogen atom, 5 R10 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, and R" and R 12 independently represent a Cl-C6 alkyl group optionally substituted with at least one halogen atom), J is a group represented by J1 or J2: (Rl bq J a J2 'R}E 10,Z xR1 3 b 10 413a (wherein Xa is CH or a nitrogen atom, Ya is CH, Za is CH or a nitrogen atom, Xb is CH or a nitrogen atom, Yb is CH, and Zb is CH or a nitrogen atom,

R

13 a is a Cl-C6 alkyl group optionally substituted with at 15 least one halogen atom; a C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group; a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting 20 of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally ,26 substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group pptionally substituted with at least one halogen atom and (8) a Cl-C6' 5 alkylsulfonyl group optionally substituted with at least one halogen atom; or a 5- to 6-membered heteroaryl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally 10 substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, R1 3 b is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 15 R is a halogen atom; a cyano group; a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a Cl-C6 alkylthio group optionally substituted with at least one halogen atom; a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom; a Cl-C6 20 alkylsulfonyl group optionally substituted with at least one halogen atom; or a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at 25 least one halogen atom and (5) a Cl-C6 alkoxy group optionally 27 substituted with at least one halogen atom, R14b is a C1-C6 alkyl group optionally substituted with at least one halogen atom; or a phenyl group optionally substituted with 1 to 5 independent substituents selected from 5 the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least.one halogen atom, 10 p is an integer of 0 to 2, ,q is 1, (provided that, when p is 2, two R 14 a's may be the same or different)), and A' and A 2 are an oxygen atom. 15 (16) A hydrazide compound represented by the formula (1-1): R1 4 ay Rien Rise R 1a O R 1 sb 4a0 N R 18b

R

4 b N 1 X( R R4C C-NR 2 -NR 3 f-M 4dOO wherein 28 Ri is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R2 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 5 R 3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, Ra is a hydrogen atom, a halogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 10 alkoxy group optionally substituted with at least one halogen atom,, or a phenyl group optionally substituted with at least one halogen atom, R 4, R 4 c and R are independently a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted 15 with at least one halogen atom, or R4b and R 4 c are bound to each other at their terminal ends to form a group: -CR 41

=CR

4 2

-CR

43

=CR

44 (wherein R 41 , R 4 2 , R 43 and R 44 represent a hydrogen atom), 6 7 8 M is OR , SR or NR'R9 20 (wherein R 6 and R 7 are a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted 25 with at least one halogen atom, 29 Re and R 9 are independently a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, a C3-C6 alkynyl group optionally substituted with' 5 at least one halogen atom, or Re and R 9 are taken together with the nitrogen atom to which they are bound to form a pyrrolidin-1-yl group, a piperidino group, a hexamethyleneimin-1-yl group, a heptamethyleneimin-1-yl group, a morpholino group, a 10 thiomorpholin-4-yl group, or a 4-phenylpiperazin-1-yl group), Xa is a nitrogen atom or CRi 4 ax (wherein Ri1ax represents a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally 15 substituted with at least one halogen atom, or a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom),

R

14 ay is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one 20 halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, or a phenyl group, 25 R14az is a hydrogen atom, .30

X

18 is a nitrogen atom or CR8e (wherein R 1* is a hydrogen atom or a halogen atom), and Ri a, R Bb, RiC and R1 d are independently a hydrogen atom or a halogen atom. 5 (17) A hydrazide compound represented by the formula (1-1): R 14ay R1 4 az X8 R 1a 4a0 N \xR18b R 1

R

4 N 1 X(f R 18d

R

4 C -NR 2

-NR

3 3--TM 0 0 wherein R1 is a hydrogen atom, or a Cl-C6 alkyl group optionally 10 substituted with at least one halogen atom,

R

2 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least ond halogen atom,

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 15 alkoxycarbonyl group, R4a is a hydrogen atom, a halogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, or a phenyl group optionally substituted with at least 20 one halogen atom, 31 R 4, R 4 c and R are independently a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or R Q and R4c are bound to each other at their terminal ends' 5 to form a group: -CR 4

=CR

42

-CR

43 =CR 44 (wherein R 41 , R 42 , R 43 and R 44 represent a hydrogen atom), M is a hydrogen atom, Xa is a nitorogen atom or CRi 4 ax (wherein R 14 ax is a hydrogen atom, a halogen atom, a cyano group, 10 a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one 15 halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom), R14ay is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted 20 with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, or a phenyl group,

R

1 4az is a hydrogen atom, 25 X is a nitrogen atom or CR18e (wherein R1B* is a hydrogen atom or a halogen atom), and Risa, Rl b, RlB* and Rid are independently a hydrogen atom or a halogen atom. (18) A hydrazide compound represented by the formula (II): R14ay R14az Xa R 1a NII~ 4a 0 R18b R 4b N i ,., X R 0 1 NBd R1 /R R18 R18 R 4

C-NR

2

--NH

2 Re 0 wherein

R

1 ~ represents a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R2-i represents a hydrogen atom or a methyl group, R4a represents a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

4 b, R 4 c and R*d independently, represent a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or R 4 b and R 4 C are bound to each other at their terminal ends to form Tl: -CR41=CR 4 2

-CR

43 =CR 44 (wherein

R

4 , R4 2 , R' and R 44 , each, independently, represent a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom), ,33 Xa represents a nitrogen atom or CR 1a (wherein R 4ax represents a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally 5 substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom), 10 R 4 ay and R1 4 az independently represent a hydrogen atom, a halogen atom, a cyano group, a C1-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one 15 halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, X18 represents a nitrogen atom or CR 8", 20 (wherein Rie represents a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom) Risa represents a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, and 25 R 18b, R 18C and R d independently represent a hydrogen atom, .34 a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom. (19) The compound according to the above (18), wherein R2-1 is a methyl group. 5 (20) A pesticide comprising the compound according to any one of the above (1) to (17) as an active ingredient. (21) A method of controlling a pest which comprises applying the compound according to any one of the above (1) to (17) directly to a pest or to a place where a pest inhabits. 10 (22) Use of the compound according to any one of the above (1) to (17) for controlling a pest. (23) Use of the compound according to any one of the above (1) to (17) for manufacturing a pesticidal preparation. 15 Hereinafter, preferred embodiments of the present invention will be illustrated.

R

14 a used herein represents a group which can substitute for a hydrogen atom of a ring constituting CH of a group represented by J1, and R1 4 b represents a group which can 20 substitute for a hydrogen atom of a ring constituting CH of a group represented by J2. In the present invention, examples of a halogen atom include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. 25 In R', R 2 and R 3 , examples of the "Cl-C6 alkyl group .35 optionally substituted with at least one halogen atom" include a methyl group, an ethyl group, a 2,2,2-trifluoroethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group' 5 and a hexyl group. In R 1 , examples of the "C2-C6 cyanoalkyl group" include a cyanomethyl group and a 2-cyanoethyl group; examples of the "C2-C6 alkoxyalkyl group optionally substituted with at least one halogen atom" include a 10 2-methoxyethyl group, a 2-ethoxyethyl group and a 2-isopropyloxyethyl group; examples of the "C2-C6 alkenyl group optionally substituted with at least one halogen atom" include a 2-propenyl group, a 3-chloro-2-propenyl group, a 15 2-chloro-2-propenyl group, a 3,3-dichloro-2-propenyl group, a 2-butenyl group, a 3-butenyl group, a 2-methyl-2-propenyl group, a 3-methyl-2-butenyl group, a 2-pentenyl group and a 2-hexenyl group; example of the "C3-C6 alkynyl group optionally 20 substituted with at least one halogen atom" include a 2-propynyl group, a 3-chloro-2-propynyl group, a 3-bromo-2-propynyl group, a 2-butynyl group and a 3-butynyl group; and examples of the "C7-C9 phenylalkyl group whose benzene 25 ring moiety may be substituted with 1 to 5 independent groups 36 selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one' 5 halogen atom" include a, benzyl group, a 1-phenylethyl group, a 2-phenylethyl group, a 2-chlorobenzyl group, a 3-chlorobenzyl group, a 4-chlorobenzyl group, a 2-cyanobenzyl group, a 3-cyanobenzyl group, a 4-cyanobenzyl group, a 2-nitrobenzyl group, a 3-nitrobenzyl group, a 4-nitrobenzyl 10 group, a 2-methylbenzyl group, a 3-methylbenzyl group, a 4-methylbenzyl group, a 2-(trifluoromethyl)benzyl group, a 3-(trifluoromethyl)benzyl group, a 4-(trifluoromethyl)benzyl group, a 2-methoxybenzyl group, a 3-methoxybenzyl group and a 4-methoxybenzyl group. 15 In R 2 and R3, examples of the "Cl-C6 acyl group" include a formyl group, an acetyl group, a propionyl group, an isobutyryl group and a trimethylacetyl group; examples of the "C2-C6 alkoxycarbonyl group" include a methoxycarbonyl group, an ethoxycarbonyl group, an 20 isopropoxycarbonyl group and a tert-butoxycarbonyl group; examples of the "C3-C7 N,N-dialkylcarbamoyl group" include a N,N-dimethylcarbamoyl group and a N,N-diethylcarbamoyl group; and examples of the "phenyl group optionally substituted with 25 1 to 5 independent groups selected from the group consisting 37 of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkyl group optionally substituted with at least one halogen atom" include a phenyl' 5 group, a 2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 2-cyanophenyl group, a 3-cyanophenyl group, a 4-cyanophenyl group, a 2-nitrophenyl group, a 3-nitrophenyl group, a 4-nitrophenyl group, a 2-methylphenyl group, a 3-methylphenyl group, a 4-methylphenyl group, a 10 2-(trifluoromethyl)phenyl group, a 3-(trifluoromethyl)phenyl group and a 4-(trifluoromethyl)phenyl group. In R 4 , R 41 , R 42 , R 4 and R 4 4 , examples of the "Cl-C6 alkyl group optionally substituted with at least one halogen atom" include a methyl group, a trifluoromethyl group, an ethyl group, 15 a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group and a hexyl group. In R 4 , R, 41

R

42 , R 43 and R44, examples of the "Cl-C6 alkoxy group optionally substituted with at least one halogen atom" 20 include a methoxy group, a trifluoromethoxy group, an ethoxy group, a 2,2,2-trifluoroethoxy group, a propyloxy group, an isopropyloxy group, a butoxy group, an isobutyloxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group and a hexyloxy group. 25 In R 4 , R 41 , R 42 , R 4 3 and R 44 , examples of the "Cl-C6 alkylthio 38 group optionally substituted with at least one halogen atom" include a methylthio group, a trifluoromethylthio group and an ethylthio group. In R 4 , R 41 , R 42 , R 43 and R 44 , examples of the "Cl-C6 5 alkylsulfinyl group optionally substituted with at least one halogen atom" include a methylsulfinyl group, a trifluoromethylsulfinyl group and an ethylsulfinyl group. In R 4 , R 4 1 , R 42 , R 43 and R 44 , examples of the "Cl-C6 alkylsulfonyl group optionally substituted with at least one 10 halogen atom" include a methylsulfonyl group, a trifluoromethylsulfonyl group and an ethylsulfonyl group. In R 4 , examples of the "phenyl group optionally substituted with at least one halogen atom" include a phenyl group, a 2-chlorophenyl group, a 3-chlorophenyl group and a 15 4-chlorophenyl group. In R 45 and R 46 , examples of the "Cl-C6 alkyl group optionally substituted with at least one halogen atom" include a methyl group, a trifluoromethyl group, and an ethyl group. In R 5 , examples of the "C2-C6 alkenyl group optionally 20 substituted with at least one halogen atom" include a vinyl group, a 1-propenyl group, a 2-propenyl group, a 1-methylvinyl group, a 2-chlorovinyl group and a 2-methyl-1-propenyl group; examples of the "C2-C6 alkynyl group optionally substituted with at least one halogen atom" include an ethynyl 25 group; 39 examples of the "Cl-C6 alkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a Cl-C6 alkoxy group, (3) a Cl-C6 alkylthio group, (4) a Cl-C6 alkylsulfinyl group,' 5 (5) a Cl-C6 alkylsulfonyl group, (6) a C2-C6 dialkylamino group and (7) a C3-C6 cycloalkyl group" include a methyl group, a trifluoromethyl group, a trichloromethyl group, a chloromethyl group, a dichloromethyl group, a fluoromethyl group, a difluoromethyl group, a methoxymethyl group, an ethoxymethyl 10 group, a methylthiomethyl group, an ethylthiomethyl group, a methy;sulfinylmethyl group, a methylsulfonylmethyl group, a dimethylaminomethyl group, a cyclopropylmethyl group, a cyclopentylmethyl group, a cyclohexylmethyl group, an ethyl group, a pentafluoroethyl group, a propyl group, an isopropyl 15 group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group and a hexyl group; examples of the "C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 20 alkyl group" include a cyclopropyl group, a 2-methylcyclopropyl group, a cyclobutyl group, a cyclopentyl group and a cyclohexyl group; examples of the "phenyl group optionally substituted with 1 to 5 independent substituents selected from the group 25 consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro 40 group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one 5 halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, (8) a C1-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally substituted with at least one halogen atom and (10) a C2-C6 10 alkoxycarbonyl group optionally substituted with at least one halogen atom" include a phenyl group, a 2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 4-fluorophenyl group, a 4-bromophenyl group, a 4-iodophenyl group, a 2-cyanophenyl group, a 3-cyanophenyl group, a 15 4-cyanophenyl group, a 2-nitrophenyl group, a 3-nitrophenyl group, a 4-nitrophenyl group, a 2-methylphenyl group, a 3-methylphenyl group, a 4-methylphenyl group, a 2- (trifluoromethyl)phenyl group, a 3- (trifluoromethyl)phenyl group, a 4-(trifluoromethyl)phenyl group, a 2-methoxyphenyl 20 group, a 3-methoxyphenyl group, a 4-methoxyphenyl group, a 4-(trifluoromethoxy)phenyl group, a 4-(methylthio)phenyl group, a 4-(methylsulfinyl)phenyl group, a 4-(methylsulfonyl)phenyl group and a 4-(methoxycarbonyl)phenyl group; 25 examples of the "naphthyl group optionally substituted .41 with 1 to 9 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally 5 substituted with at least one halogen atom" include a 1-naphthyl and a 2-naphthyl group; examples of the "5- to 6-membered heteroaryl group optionally substituted with one or more independent substituents selected from the group (1) a halogen atom, (2) 10 a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom" include a 1-methyl-2-pyrrolyl group, a 2-furyl group, a 3-furyl group, a 5-bromo-2-furyl group, a 15 5-nitro-2-furyl group, a 2-methyl-3-furyl group, a 2,5-dimethyl-3-furyl group, a 2,4-dimethyl-3-furyl group, a 2-thienyl group, a 3-thienyl group, a 5-methyl-2-thienyl group, a 3-methyl-2-thienyl group, a 1-methyl-3-trifluoromethyl-5-pyrazolyl group, a 20 5-chloro-1, 3-dimethyl-4-pyrazolyl group, a 2-pyridinyl group, a 3-pyridinyl group, a 4-pyridinyl group, a 2-methyl-3-pyridinyl group, a 6-methyl-3-pyridinyl group, a 2-chloro-3-pyridinyl group, a 6-chloro-3-pyridinyl group and a pyrazinyl group; 25 examples of the "3- to 8-membered non-aromatic 42 heterocyclic group optionally substituted with one or more independent substituents selected from a group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group" include a tetrahydro-2-furyl group, a tetrahydro-3-furyl group, and a' 5 morpholino group; examples of the "C7-C9 phenylalkyl group whose benzene ring moiety may be substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 10 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom" include a benzyl group, a 1-phenylethyl group, a 2-phenylethyl group, a 2-chlorobenzyl group, a 3-chlorobenzyl group, a 4-chlorobenzyl group, a 15 2-cyanobenzyl group, a 3-cyanobenzyl group, a 4-cyanobenzyl group, a 2-nitrobenzyl group, a 3-nitrobenzyl group, a 4-nitrobenzyl group, a 2-methylbenzyl group, a 3-methylbenzyl group, a 4-methylbenzyl group, a 2-(trifluoromethyl)benzyl group, a 3-(trifluoromethyl)benzyl group, a 20 4-(trifluoromethyl)benzyl group, a 2-methoxybenzyl group, a 3-methoxybenzyl group and a 4-methoxybenzyl group; and examples of the "C7-C9 phenoxyalkyl group whose benzene ring moiety may be substituted with 1 to 5 independent substituents selected from the group consisting of (1) a 25 halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 -43 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom" include a phenoxymethyl group, a 2-phenoxyethyl group and a 1-phenoxyethyl group. 5 In R 6 and R 7 , examples of the "Cl-C6 alkyl group optionally substituted with at least one halogen atom" include a methyl group, an ethyl group, a 2,2,2-trifluoroethyl group, a 2, 2, 2-trichloroethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a 10 tert-butyl group, a pentyl group and a hexyl group; examples of the "C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom" include a 2-methoxyethyl group, 2-ethoxyethyl group and a 2-isopropyloxyethyl group; 15 examples of the "C2-C6 alkenyl group optionally substituted with at least one halogen atom" include a 1-propenyl group, a 2-propenyl group, a 3-chloro-2-propenyl group, a 2-chloro-2-propenyl group, a 3, 3-dichloro-2-propenyl group, a 2-butenyl group, a 3-butenyl group, a 20 2-methyl-2-propenyl group, a 3-methyl-2-butenyl group, a 2-pentenyl group and a 2-hexenyl group; examples of the "C3-C6 alkynyl group optionally substituted with at least one halogen atom" include a 2-propynyl group, a 3-chloro-2-propynyl group, a 25 3-bromo-2-propynyl group, a 2-butynyl group and a 3-butynyl '44 group; examples of the "C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 5 alkyl group" include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group and a cyclohexyl group; examples of the "phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of the (1) a halogen atom, (2) a cyano group, (3) 10 a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally 15 substituted with at least one halogen atom, (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally substituted with at least one halogen atom and (10),a C2-C6 alkoxycarbonyl group optionally substituted with at least one 20 halogen atom" include a phenyl group, a 2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 4-fluorophenyl group, a 4-bromophenyl group, a 4-iodophenyl group, a 2-cyanophenyl group, a 3-cyanophenyl group, a 4-cyanophenyl group, a 2-nitrophenyl group, a 3-nitrophenyl 25 group, a 4-nitrophenyl group, a 2-methylphenyl group, a 45 3-methylphenyl group, a 4-methylphenyl group, a 2- (trifluoromethyl) phenyl group, a 3- (trifluoromethyl) phenyl group, a 4-(trifluoromethyl)phenyl group, a 2-methoxyphenyl group, a 3-methoxyphenyl group, a 4-methoxyphenyl group, a' 5 4-(trifluoromethoxy)phenyl group, a 4-(methylthio)phenyl group, a 4-(methylsulfinyl)phenyl group, a 4-(methylsulfonyl)phenyl group and a 4-(methoxycarbonyl)phenyl group; examples of the "5- to 6-membered heteroaryl group 10 optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one 15 halogen atom" include a 2-pyridinyl group; and examples of the "C7-C9 phenylalkyl group whose benzene ring moiety may be substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a C1-C6 20 alkyl group optionally substituted with at least one halogen atom and (5) a C1-C6 alkoxy group optionally substituted with at least one halogen atom" include a benzyl group, a 1-phenylethyl group, a 2-phenylethyl group, a 2-chlorobenzyl group, a 3-chlorobenzyl group, a 4-chlorobenzyl group, a 25 2-cyanobenzyl group, a 3-cyanobenzyl group, a 4-cyanobenzyl 46 group, a 2-nitrobenzyl group, a 3-nitrobenzyl group, a 4-nitrobenzyl group, a 2-methylbenzyl group, a 3-methylbenzyl group, a 4-methylbenzyl group, a 2-(trifluoromethyl)benzyl group, a 3-(trifluoromethyl)benzyl group, a 5 4-(trifluoromethyl)benzyl group, a 2-methoxybenzyl group, a 3-methoxybenzyl group and a 4-methoxybenzyl group. In Re and R 9 , examples of the "Cl-C6 alkyl group optionally substituted with at least one halogen atom" include a methyl group, an ethyl group, a 2,2,2-trifluoroethyl group, a LO 2, 2, 2-trichloroethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group and a hexyl group; examples of the "C2-C6 alkoxyalkyl group optionally substituted with at least one halogen atom" include a 15 2-methoxyethyl group, a 2-ethoxyethyl group and a 2-isopropyloxyethyl group; examples of the "C2-C6 alkenyl group optionally substituted with at least one halogen atom" include a 2-propenyl group, a 3-chloro-2-propenyl group, a 20 2-chloro-2-propenyl group, a 3, 3-dichloro-2-propenyl group, a 2-butenyl group, a 3-butenyl group, a 2-methyl-2-propenyl group, a 3-methyl-2-butenyl group, a 2-pentenyl group and a 2-hexenyl group; examples of the "C3-C6 alkynyl group optionally 25 substituted with at least one halogen atom" include a .47 2-propynyl group, a 3-chloro-2-propynyl group, a 3-bromo-2-propynyl group, a 2-butynyl group and a 3-butynyl group; examples of the "C3-C6 cycloalkyl group optionally 5 substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group and a cyclohexyl group; examples of the "phenyl group optionally substituted with 10 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group, optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, (6) a Cl-C6 15 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally 20 substituted with at least one halogen atom and (10) a C2-C6 alkoxycarbonyl group optionally substituted with at least one halogen atom" include a phenyl group, a 2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 4-fluorophenyl group, a 4-bromophenyl group, a 4-iodophenyl 25 group, a 2-cyanophenyl group, a 3-cyanophenyl group, a 48 4-cyanophenyl group, a 2-nitrophenyl group, a 3-nitrophenyl group, a 4-nitrophenyl group, a 2-methylphenyl group, a 3-methylphenyl group, a 4-methylphenyl group, a 2- (trifluoromethyl) phenyl group, a 3- (trifluoromethyl)phenyl' 5 group, a 4-(trifluoromethyl)phenyl group, a 2-methoxyphenyl group, a 3-methoxyphenyl group, a 4-methoxyphenyl group, a 4-(trifluoromethoxy)phenyl group, a 4-(methylthio)phenyl group, a 4-(methylsulfinyl)phenyl group, a 4-(methylsulfonyl)phenyl group and a 10 4-(methoxycarbonyl)phenyl group; ,xamples of the "5- to 6-membered heteroaryl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group 15 optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom" include a 3-pyridinyl group; examples of the "C7-C9 phenylalkyl group whose benzene ring moiety may be substituted with 1 to 5 independent 20 substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom" include a benzyl group, a 25 1-phenylethyl group, a 2-phenylethyl group, a 2-chlorobenzyl .49 group, a 3-chlorobenzyl group, a 4-chlorobenzyl group, a 2-cyanobenzyl group, a 3-cyanobenzyl group, a 4-cyanobenzyl group, a 2-nitrobenzyl group, a 3-nitrobenzyl group, a 4-nitrobenzyl group, a 2-methylbenzyl group, a 3-methylbenzyl' 5 group, a 4-methylbenzyl group, a 2-(trifluoromethyl)benzyl group, a 3-(trifluoromethyl)benzyl group, a 4-(trifluoromethyl)benzyl group, a 2-methoxybenzyl group, a 3-methoxybenzyl group and a 4-methoxybenzyl group; and examples of the "3- to 8-membered non-aromatic 10 heterocyclic group" when "Re and R 9 are taken together with the nitrogen atom to which they are bound to form a 3- to 8-membered non-aromatic heterocyclic group" include a pyrrolidin-1-yl group, piperidino group, a 3,5-dimethylpiperidino group, a hexamethyleneimin-1-yl group, a heptamethyleneimin-1-yl group, 15 a morpholino group, a 2,6-dimethylmorpholino group, a thiomorpholin-4-yl group, a 4-methylpiperazin-1-yl group, a 4-(ethoxycarbonyl)piperazin-1-yl group and a 4-phenylpiperazin-1-yl group. In R10, examples of the "Cl-C6 alkyl group optionally 20 substituted with at least one halogen atom" include a methyl group, a trifluoromethyl group, a trichloromethyl group, an ethyl group, a 2-chloroethyl group, a 2,2,2-trifluoroethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl 25 group and a hexyl group; 50 ' examples of the "C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group optionally substituted with at least one halogen' 5 atom" include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group and a cyclohexyl group; and examples of the "phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro 10 group, (4) a Cl-C6 alkyl group optionally substituted with at leastone halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom" include a phenyl group, a 4-chlorophenyl group, a 4-nitrophenyl group and a 4-methylphenyl group. 15 In R 11 and R 12 , examples of the "Cl-C6 alkyl group optionally substituted with at least one halogen atom" include a methyl group, an ethyl group, a 2,2,2-trifluoroethyl group, a 2,2,2-trichloroethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a 20 tert-butyl group, a pentyl group and a hexyl group; examples of the "C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group optionally substituted with at least one halogen 25 atom" include a cyclopropyl group, a cyclobutyl group, a .51 cyclopentyl group and a cyclohexyl group; examples of the "phenyl group optionally substituted with 1 to 5 independent groups selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group,' 5 (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom" include a phenyl group and a 4-methylphenyl group; and examples of the "3- to 8-membered non-aromatic 10 heterocyclic group" when "R 11 and R 12 are taken together with the nitrogen atom to which they are bound to form a 3- to 8-membered non-aromatic heterocyclic group" include a pyrrolidin-1-yl group, a piperidino group, a 3,5-dimethylpiperidino group, a morpholino group, a 15 2,6-dimethylmorpholino group, a thiomorpholin-4-yl group, a 4-methylpiperazin-1-yl group, a 4-(ethoxycarbonyl)piperazin-1-yl group and a 4-phenylpiperazin-1-yl group. In R 3 a and R 3 b, examples of the "Cl-C6 alkyl group 20 optionally substituted with at least one halogen atom" include a methyl group, a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, an ethyl group, a 2,2,2-trifluoroethyl group, a 1, 1,2,2-tetrafluoroethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl 25 group, a sec-butyl group, a tert-butyl group, a pentyl group .52 , and a hexyl group; examples of the "C2-C6 cyanoalkyl group" include a cyanomethyl group and a 2-cyanoethyl group; examples of the "C2-C6 alkoxyalkyl group optionally 5 substituted with at least one halogen atom" include a methoxymethyl group, an ethoxymethyl group, a 2-methoxyethyl group, a 2-ethoxyethyl group and a 2-isopropyloxyethyl group; examples of the "C2-C6 alkenyl group optionally substituted with at least one halogen atom" include a 10 2-propenyl group, a 3-chloro-2-propenyl group, a 2-chloro-2-propenyl group, a 3, 3-dichloro-2-propenyl group, a 2-butenyl group, a 3-butenyl ,group, a 2-methyl-2-propenyl group, a 3-methyl-2-butenyl group, a 2-pentenyl group and a 2-hexenyl group; 15 examples of the "C2-C6 alkynyl group optionally substituted with at least one halogen atom" include a 2-propynyl group, a 3-chloro-2-propynyl group, a 3-bromo-2-propynyl group, a 2-butynyl group and a 3-butynyl group; 20 examples of the "C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group" include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group and a cyclohexyl group; 25 examples of the "phenyl group optionally substituted with 53 1 to 5 independent substituents selected from a group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally' 5 substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom and (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one 10 halogen atom" include a phenyl group, a 2-fluorophenyl group, a 3-fluorophenyl group, a 4-fluorophenyl group, a 2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 2-bromophenyl group, a 2-iodophenyl group, a 2,6-difluorophenyl group, a 2,6-dichlorophenyl group, a 15 2-chloro-6-fluorophenyl group, a 2-chloro-4-fluorophenyl group, a 2-cyanophenyl group, a 3-cyanophenyl group, a 4-cyanophenyl group, a 2-nitrophenyl group, a 3-nitrophenyl group, a 4-nitrophenyl group, a 2-methylphenyl group, a 3-methylphenyl group, a 4-methylphenyl group, a 2-ethylphenyl 20 group, a 2-isopropylphenyl group, a 2-tert-butylphenyl group, a 2-(trifluoromethyl)phenyl group, a 3- (trifluoromethyl)phenyl group, a 4- (trifluoromethyl)phenyl group, a 2-methoxyphenyl group, a 3-methoxyphenyl group, a 4-methoxyphenyl group, a 2-ethoxyphenyl group, a 25 2-(trifluoromethoxy)phenyl group, a 2-(methylthio)phenyl .54 group, a 2-(methylsulfinyl)phenyl group and a 2-(methylsulfonyl)phenyl group; examples of the "5- to 6-membered heteroaryl group optionally substituted with one or more independent 5 substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom" include a 2-pyridinyl group, a 10 3-fluoro-2-pyridinyl group, a 3-chloro-2-pyridinyl group, a 3-bromo-2-pyridinyl group, a 3-iodo-2-pyridinyl group, a 3-methyl-2-pyridinyl group, a 3-trifluoromethyl-2-pyridinyl group, a 3-methoxy-2-pyridinyl group, a 3-cyano-2-pyridinyl group, a 3-nitro-2-pyridinyl group, a 3-pyridinyl group, a 15 2-chloro-3-pyridinyl group, a 4-chloro-3-pyridinyl group, a 4-pyridinyl group, a 3-chloro-4-pyridinyl group, a 3,5-dichloro-4-pyridinyl group, a 2-pyrimidinyl group, a 4-methyl-2-pyrimidinyl group, a 4,6-dimethyl-2-pyrimidinyl group, a 4-pyrimidinyl group, a 5-chloro-4-pyrimidinyl group, 20 a pyrazinyl group, a 3-methyl-2-pyrazinyl group, a 2-thiazolyl group, a 1-methyl-5-pyrazolyl group, a 4-chloro-1-methyl-5-pyrazolyl group, a 4-chloro-1,3-dimethyl-5-pyrazolyl group and a 4-chloro-5-methyl-3-isooxazolyl group; 25 examples of the "C7-C9 phenylalkyl group whose benzene .55 ring moiety may be substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen' 5 atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom" include a benzyl group, a 1-phenylethyl group, a 2-phenylethyl group, a 2-chlorobenzyl group, a 3-chlorobenzyl group, a 4-chlorobenzyl group, a 2-cyanobenzyl group, a 3-cyanobenzyl group, a 4-cyanobenzyl 10 group, a 2-nitrobenzyl group, a 3-nitrobenzyl group, a 4-nitrobenzyl group, a 2-methylbenzyl group, a 3-methylbenzyl group, a 4-methylbenzyl group, a 2-(trifluoromethyl)benzyl group, a 3-(trifluoromethyl)benzyl group, a 4-(trifluoromethyl)benzyl group, a 2-methoxybenzyl group, a 15 3-methoxybenzyl group and a 4-methoxybenzyl group; and examples of the "C7-C9 pyridinylalkyl group whose pyridine ring moiety may be substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) 20 a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom" include a 2-pyridinylmethyl group, a 3-pyridinylmethyl group, a 4-pyridinylmethyl group, a 3-chloro-2-pyridinylmethyl group, 25 and a 2-chloro-3-pyridinylmethyl group.

56 In R 1 1a and R 11, examples of the "C1-C6 alkyl group optionally substituted with at least one halogen atom" include a methyl group, a trifluoromethyl group, a trichloromethyl group, a chloromethyl group, a dichloromethyl group, a 5 fluoromethyl group, a difluoromethyl group, an ethyl group, a pentafluoroethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group and a hexyl group; examples of the "Cl-C6 alkoxy group optionally 10 substituted with at least one halogen atom" include a methoxy group, an ethoxy group, a 2,2,2-trifluoroethoxy group, a propoxy group, an isopropyloxy group, a butoxy group, an isobutyloxy group, a sec-butoxy group and a tert-butoxy group; examples of the "C2-C6 cyanoalkyloxy group" include a 15 cyanomethoxy group and a 2-cyanoethoxy group; examples of the "C3-C6 alkoxyalkyloxy group optionally substituted with at least one halogen atom" include a 2-(methoxy)ethoxy group; examples of the "C3-C6 alkenyloxy group optionally 20 substituted with at least one halogen atom" include a 2-propenyloxy group and a 2-methyl-2-propenyloxy group; examples of the "C3-C6 alkynyloxy group optionally substituted with at least one halogen atom" include a 2-propynyloxy group and a 2-butynyloxy group; 25 examples of the "Cl-C6 alkylthio group optionally ,57 substituted with at least one halogen atom" include a methylthio group, a trifluoromethylthio group, an ethylthio group, a propylthio group, an isopropylthio group, a butylthio group, an isobutylthio group, a sec-butylthio group, a 5 tert-butylthio group, a pentylthio group and a hexylthio group; examples of the "Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom" include a methylsulfinyl group, a trifluoromethylsulfinyl group, an ethylsulfinyl group, a propylsulfinyl group, an 10 isopropylsulfinyl group, a butylsulfinyl group, an isobutylsulfinyl group, a sec-butylsulfinyl group, a tert-butylsulfinyl group, a pentylsulfinyl group and a hexylsulfinyl group; examples of the "Cl-C6 alkylsulfonyl group optionally 15 substituted with at least one halogen atom" include a methylsulfonyl group, a trifluoromethylsulfonyl group, an ethylsulfonyl group, a propylsulfonyl group, an isopropylsulfonyl group, a butylsulfonyl group, an isobutylsulfonyl group, a sec-butylsulfonyl group, a 20 tert-butylsulfonyl group, a pentylsulfonyl group and a hexylsulfonyl group; examples of the "phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro 25 group, (4) a Cl-C6 alkyl group optionally substituted with at 58 least one halogen atom and (5) a C1-C6 alkoxy group optionally substituted with at least one halogen atom" include a phenyl group, a 2-chlorophenyl group, a 3-chlorophenyl group, a 4-chlorophenyl group, a 4-fluorophenyl group, a 4-bromophenyl' 5 group, a 4-iodophenyl group, a 2-cyanophenyl group, a 3-cyanophenyl group, a 4-cyanophenyl group, a 2-nitrophenyl group, a 3-nitrophenyl group, a 4-nitrophenyl group, a 2-methylphenyl group, a 3-methylphenyl group, a 4-methylphenyl group, a 2-(trifluoromethyl)phenyl group, a 10 3-(trifluoromethyl)phenyl group, a 4-(trifluoromethyl)phenyl group, a 2-methoxyphenyl group, a 3-methoxyphenyl group, a 4-methoxyphenyl group and a 4-(trifluoromethoxy)phenyl group; examples of the "5- to 6-membered heteroaryl group optionally substituted with one or more independent 15 substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom" include a 2-furyl group, a 3-furyl 20 group, a 2-pyridinyl group, a 3-pyridinyl group, a 4-pyridinyl group and a pyrazinyl group; and examples of the "phenoxy group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro 25 group, (4) a Cl-C6 alkyl group optionally substituted with at 59 least one halogen atom and (5) a C1-C6 alkoxy group optionally substituted with at least one halogen atom" include a phenoxy group, a 2-chlorophenoxy group, a 3-chlorophenoxy group, a 4-chlorophenoxy group, a 2-cyanophenoxy group, a 5 3-cyanophenoxy group, a 4-cyanophenoxy group, a 2-nitrophenoxy group, a 3-nitrophenoxy group, a 4-nitrophenoxy group, a 2-methylphenoxy group, a 3-methylphenoxy group, a 4-methylphenoxy group, a 2-(trifluoromethyl)phenoxy group, a 3-(trifluoromethyl)phenoxy group, a 10 4- (trifluoromethyl) phenoxy group, a 2-methoxyphenoxy group, a 3-methoxyphenoxy group, a 4-methoxyphenoxy group and a 4-(trifluoromethoxy)phenoxy group. Examples of the group represented by J1 include a 1-phenylpyrazol-5-yl group, a 1-(2-chlorophenyl)pyrazol-5-yl 15 group, a 1-(2-pyridinyl)pyrazol-5-yl group, a 1-(3-chloro-2-pyridinyl)pyrazol-5-yl, a 3-fluoro-1-phenylpyrazol-5-yl group, a 1-(2-chlorophenyl)-3-fluoropyrazol-5-yl group, a 3-fluoro-1-(2-pyridinyl)pyrazol-5-yl group, a 20 3-fluoro-l-(3-chloro-2-pyridinyl)pyrazol-5-yl group, a 3-chloro- 1-phenylpyrazol-5-yl group, a 3-chloro-1-(2 chlorophenyl)pyrazol-5-yl group, a 3-chloro-1-(2 pyridinyl)pyrazol-5-yl group, a 3-chloro-1-(3-chloro-2-pyridinyl)pyrazol-5-yl group, a 25 3-bromo-1-phenylpyrazol-5-yl group, a 6O 3-bromo-1-(2-chlorophenyl)pyrazol-5-yl group, a 3-bromo-1-(2-pyridinyl)pyrazol-5-yl group, a 3-bromo-1-(3-chloro-2-pyridinyl)pyrazol-5-yl group, a 3-iodo-1-phenylpyrazol-5-yl group, a 5 3-iodo-1-(2-chlorophenyl)pyrazol-5-yl group, a 3-iodo-1-(2-pyridinyl)pyrazol-5-yl group, a 3-iodo-1-(3-chloro-2-pyridinyl)pyrazol-5-yl group, a 3-methyl-1-phenylpyrazol-5-yl group, a 1-(2-chlorophenyl)-3-methylpyrazol-5-yl group, a 10 3-methyl-1-(2-pyridinyl)pyrazol-5-yl group, a 1-(3-phloro-2-pyridinyl)-3-methylpyrazol-5-yl group, a 1-phenyl-3-(trifluoromethyl)pyrazol-5-yl group, a 1-(2-chlorophenyl)-3-(trifluoromethyl)pyrazol-5-yl group, a 1-(2-pyridinyl)-3-(trifluoromethyl)pyrazol-5-yl group, a 15 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)pyrazol-5-yl group, a 3-chloro-1-methylpyraiol-5-yl group, a 3-chloro-1-ethylpyrazol-5-yl group, a 3-chloro-1-isopropylpyrazol-5-yl group, a 20 1-tert-butyl-3-chloropyrazol-5-yl group, a 3-chloro-1-(3-fluoro-2-pyridinyl)pyrazol-5-yl group, a 1-(3-bromo-2-pyridinyl)-3-chloropyrazol-5-yl group, a 3-chloro-1-(3-iodo-2-pyridinyl)pyrazol-5-yl group, a 3-chloro-1-(3-methyl-2-pyridinyl)pyrazol-5-yl group, a 25 3-chloro-1-(3-trifluoromethyl-2-pyridinyl)pyrazol-5-yl 61 group, a 3-chloro-1-(3-methoxy-2-pyridinyl)pyrazol-5-yl group, a 3-chloro-1- (3-cyano-2-pyridinyl) pyrazol-5-yl group, a 3-chloro-1-(3-nitro-2-pyridinyl)pyrazol-5-yl group, a 3-bromo-1-methylpyrazol-5-yl group, a 5 3-bromo-1-ethylpyrazol-5-yl group, a 3-bromo-1-isopropylpyrazol-5-yl group, a 3-bromo-1-tert-butylpyrazol-5-yl group, a 3-bromo-1-(3-fluoro-2-pyridinyl)pyrazol-5-yl group, a 3-bromo-1-(3-bromo-2-pyridinyl)pyrazol-5-yl group, a 10 3-bromo-1-(3-iodo-2-pyridinyl)pyrazol-5-yl group, a 3-bromo-1-(3-methyl-2-pyridinyl)pyrazol-5-yl group, a 3-bromo-1-(3-trifluoromethyl-2-pyridinyl)pyrazol-5-yl group, a 3-bromo-1-(3-methoxy-2-pyridinyl)pyrazol-5-yl group, a 3-bromo-1-(3-cyano-2-pyridinyl)pyrazol-5-yl group, a 15 3-bromo-1-(3-nitro-2-pyridinyl)pyrazol-5-yl group, a 1-methyl-3-(trifluoromethyl)pyrazol-5-yl group, a 1-ethyl-3-(trifluoromethyl)pyrazol-5-yl group, a 1-isopropyl-3-(trifluoromethyl)pyiazol-5-yl group, a 1-tert-butyl-3-(trifluoromethyl)pyrazol-5-yl group, a 20 1-(3-fluoro-2-pyridinyl)-3-(trifluoromethyl)pyrazol-5-yl group, a 1-(3-bromo-2-pyridinyl)-3 (trifluoromethyl)pyrazol-5-yl group, a 1-(3-iodo-2 pyridinyl)-3-(trifluoromethyl)pyrazol-5-yl group, a 1-(3-methyl-2-pyridinyl)-3-(trifluoromethyl)pyrazol-5-yl 25 group, a 1-(3-trifluoromethyl-2-pyridinyl)-3- ,62 (trifluoromethyl)pyrazol-5-yl group, a 1-(3-methoxy 2-pyridinyl)-3-(trifluoromethyl)pyrazol-5-yl group, a 1-(3-cyano-2-pyridinyl)-3-(trifluoromethyl)pyrazol-5-yl group, a 1-(3-nitro-2-pyridinyl)-3-(trifluoromethyl)pyrazol 5 5-yl group, a 1-(3-chloro-2-pyridinyl)-3-ethylpyrazol-5-yl group, a 1-(3-chloro-2-pyridinyl)-3-isopropylpyrazol-5-yl group, a 3-tert-butyl-1-(3-chloro-2-pyridinyl)pyrazol-5-yl group, a 1-(3-chloro-2-pyridinyl)-3-(methylthio)pyrazol-5-yl group, a 10 1-(3-chloro-2-pyridinyl)-3-(ethylthio)pyrazol-5-yl group, a 1-(3-chloro-2-pyridinyl)-3-(isopropylthio)pyrazol-5-yl group, a 3-tert-butylthio-1-(3-chloro-2-pyridinyl)pyrazol 5-yl group, a 1-(3-chloro-2-pyridinyl)-3 (methylsulfinyl)pyrazol-5-yl group, a 15 1-(3-chloro-2-pyridinyl)-3-(ethylsulfinyl)pyrazol-5-yl group, a 1-(3-chloro-2-pyridinyl)-3 (isopropylsulfinyl)pyrazol-5'-yl group, a 3-tert-butylsulfinyl-1-(3-chloro-2'-pyridinyl)pyrazol-5-yl group, a 1-(3-chloro-2-pyridinyl)-3 20 (methylsulfonyl)pyrazol-5-yl group, a 1-(3-chloro-2 pyridinyl)-3-(ethylsulfonyl)pyrazol-5-yl group, a 1-(3-chloro-2-pyridinyl)-3-(isopropylsulfonyl)pyrazol-5-yl group, a 3-tert-butylsulfonyl-1-(3-chloro 2-pyridinyl)pyrazol-5-yl group, a 1-(3-chloro-2-pyridinyl) 25 3-(2,2,2-trifluoroethoxy)pyrazol-5-yl group, a 1-(3-chloro- ,63 2-pyridinyl) -3-cyanopyrazol-5-yl group, a 1-(2-chlorophenyl)pyrrol-2-yl group, a 1-(3-chloro 2-pyridinyl)pyrrol-2-yl group, a 4-chloro-1-(27 chlorophenyl)pyrrol- 2 -yl group, a 4-chloro-1-(3-chloro 5 2-pyridinyl)pyrrol-2-yl group, a 5-chloro-1-(2 chlorophenyl) pyrrol-2-yl group, a 5-chloro-1- (3-chloro 2-pyridinyl)pyrrol-2-yl group, a 1-(2-chlorophenyl)-4,5 dichloropyrrol-2-yl group, a 1-(3-chloro-2-pyridinyl) 4,5-dichloropyrrol-2-yl group, a 4-bromo-1-(2 10 chlorophenyl)pyrrol-2-yl group, a 4-bromo-1-(3-chloro-2 pyridinyl)pyrrol-2-yl group, a 5-bromo-1-(2 chlorophenyl) pyrrol-2-yl group, a 5-bromo-1- (3-chloro 2-pyridinyl)pyrrol-2-yl group, a 1-(2-chlorophenyl)-4,5 dibromopyrrol-2-yl group, a 1-(3-chloro-2-pyridinyl) 15 4,5-dibromopyrrol-2-yl group, a 1-(2-chlorophenyl)-4 iodopyrrol- 2 -yl group, a 1- (3-chloro-2-pyridinyl) -4 iodopyrrol-2-yl group, a 1-(2-chlorophenyl)-5 iodopyrrol-2-yl group, a 1- (3-chloro-2-pyridinyl) -5 iodopyrrol-2-yl group, a 1-(2-chlorophenyl)-4,5 20 diiodopyrrol-2-yl group, a 1-(3-chloro-2-pyridinyl)- 4 ,5 diiodopyrrol-2-yl group, a 1-(2-chlorophenyl)-4 (trifluoromethyl)pyrrol-2-yl group, a 1-(3-chloro-2 pyridinyl)-4-(trifluoromethyl)pyrrol-2-yl group, a 1- (2-chlorophenyl) -5- (trifluoromethyl)pyrrol-2-yl group, a 25 1- (3-chloro-2-pyridinyl)-5-(trifluoromethyl)pyrrol-2-yl .64 group, a 1-(2-chlorophenyl)imidazol-2-yl group, a 1-(3-chloro-2-pyridinyl)imidazol-2-yl group, a, 4-chloro-1-(2-chlorophenyl)imidazol-2-yl group, a 5 4-chloro-1-(3-chloro-2-pyridinyl)imidazol-2-yl group, a 4-bromo-1-(2-chlorophenyl)imidazol-2-yl group, a 4-bromo-1-(3'-chloro-2-pyridinyl)imidazol-2-yl group, a 1-(2-chlorophenyl)-4-(trifluoromethyl)imdazol-2-yl group, a 1-(3-chloro-2-pyridinyl)-4-(trifluoromethyl)imidazol-2-yl 10 group, a 1-(2-chlorophenyl)-1,2,4-triazol-5-yl group, a 1-(3-chloro-2-pyridinyl)-1,2,.4-triazol-5-yl group, a 3-chloro-1-(2-chlorophenyl)-1,2,4-triazol-5-yl group, a 3-chloro-1-(3-chloro-2-pyridinyl)-1,2,4-triazol-5-yl group, 15 a 3-bromo-1-(2-chlorophenyl)-1,2,4-triazol-5-yl group, a 3-bromo-1-(3-chloro-2-pyridinyl)-1, 2 , 4-triazol-5-yl group, a 1-(2-chlorophenyl)-3-(trifluoromethyl)-1,2,4-triazol-5-yl group and a 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl) 1,2,4-triazol-5-yl group. 20 Examples of the group represented by J2 include a 1-methyl-3-phenylpyrazol-4-yl group, a 3-(2-chlorophenyl)-1-methylpyrazol-4-yl group, a 1-methyl-3-(2-pyridinyl)pyrazol-4-yl group, a 3-(3-chloro-2-pyridinyl)-1-methylpyrazol-4-yl group, a 25 1-methyl-5-phenylpyrazol-4-yl group, a 65 5-(2-chlorophenyl)-1-methylpyrazol-4-yl group, a 1-methyl-5-(2-pyridinyl)pyrazol-4-yl group, a 5-(3-chloro-2-pyridinyl)-1-methylpyrazol-4-yl group, a 3-phenyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl group, a 5 3-(2-chlorophenyl)-1-(2,2,2-trifluoroethyl)pyrazol-4-yl group, a 3-(2-pyridinyl)-1-(2,2,2 trifluoroethyl)pyrazol-4-yl group, a 3-(3-chloro-2 pyridinyl)-1-(2,2,2-trifluoroethyl)pyrazol-4-yl group, a 5-phenyl-1-(2,2,2-trifluoroethyl)pyrazol-4-yl group, a 10 5-(2-chlorophenyl)-1-(2,2,2-trifluoroethyl)pyrazol-4-yl group,, a 5-(2-pyridinyl)-1-(2,2,2-trifluoroethyl)pyrazol 4-yl group, a 5-(3-chloro-2-pyridinyl)-1-(2,2,2 trifluoroethyl)pyrazol-4-yl group, a 1-(difluoromethyl)-3 phenylpyrazol-4-yl group, a 3-(2-chlorophenyl)-1 15 (difluoromethyl)pyrazol-4-yl group, a 1-(difluoromethyl) 3-(2-pyridinyl)pyrazol-4-yl group, a 3-(3-chloro-2 pyridinyl)-1-(difluoromethyl)pyrazol-4-yl group, a 1-(difluoromethyl)-5-phenylpyrazol-4-yl group, a 5-(2-chlorophenyl)-1-(difluoromethyl)pyrazol-4-yl group, a 20 1-(difluoromethyl)-5-(2-pyridinyl)pyrazol-4-yl group, a 5-(3-chloro-2-pyridinyl)-1-(difluoromethyl)pyrazol-4-yl group, a 3-(2-chlorophenyl)-1-ethylpyrazol-4-y1 group, a 3-(3-chloro-2-pyridinyl)-1-ethylpyrazol-4-yl group, a 5-(2-chlorophenyl)-1-ethylpyrazol-4-yl group, a 25 5-(3-chloro-2-pyridinyl)-1-ethylpyrazol-4-yl group, a .66 3-(2-chlorophenyl)-1-isopropylpyrazol- 4 -yl group, a 3-(3-chloro-2-pyridinyl)-1-isopropylpyrazol- 4 -yl group, a 5-(2-chlorophenyl)-1-isopropylpyrazol- 4 -yl group, a 5-(3-chloro-2-pyridinyl)-1-isopropylpyrazol- 4 -yl group, a 5 3-(2-chlorophenyl)-1-tert-butylpyrazol- 4 -yl group, a 3-(3-chloro-2-pyridinyl)-1-tert-butylpyrazol- 4 -yl group, a 5-(2-chlorophenyl)-1-tert-butylpyrazol- 4 -yl group and a 5-(3-chloro-2-p,yridinyl)-l-tert-butylpyrazol-4-yl group. As an example of the compound represented by the formula 10 (1), the following compound is mentioned: A compound of the formula (1), wherein RI is a hydrogen atom, or, a C1-C6 alkyl group optionally substituted with at least one halogen atom, R2 is a hydrogen atom, or a Cl-C6 alkyl group optionally 15 substituted with at least one halogen atom,

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, R4 is a halogen atom, a cyano group, a Cl-C6 alkyl group 20 optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a phenyl group optionally substituted with at least one halogen atom, or two R4 groups which are bound to the adjacent carbon atoms 25 are bound to each other at their terminal ends to form a group ,67 Tl: -CR 4

=CR

42

-CR

4 3

=CR

4 4 (wherein R 41 , R 42 , R 43 and R 4 4 represent a hydrogen atom), n is an integer of 0 to 3, Q is a group represented by Q1 to Q6: QI -- C(=A 31

)-R

5 Q2 -- C(=A 32 )-OR. Q3 -C(=A33)-SR 7 Q4 -- C(=A34)-NRR 9 Q5 -S() 2

-R

0 5 Q6 -S(0) 2 -NRR (wherein A 31 , A 3 2 and A 33 are an oxygen atom, A 3 4 is an oxygen atom or a sulfur atom, R5 is a hydrogen atom; a, C1-C6 alkyl group optionally substituted with one or more independent substituents selected 10 from the group consisting of (1) a halogen atom, (2) a Cl-C6 alkoxy group, (3) a Cl-C6 alkylthio group, (4) a C1-C6 alkylsulfinyl group, (5) a Cl-C6 alkylsulfonyl group, (6) a C2-C6 dialkylamino group and (7) a C3-C6 cycloalkyl group; a C3-C6 cycloalkyl group optionally substituted with one or more 15 independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group; a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group 20 optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally substituted with at least one 68 halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted wit) at least one halogen atom, (8) a Cl-C6 alkylsulfonyl group optionally 5 substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally substituted with at least one halogen atom and (10) a C2-C6 alkoxycarbonyl group optionally substituted with at least one halogen atom; a 5 to 6-membered heteroaryl group optionally substituted with one or more 10 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; or a 3- to 15 8-membered non-aromatic heterocyclic group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group,

R

6 is a Cl-C6 alkyl group optionally substituted with at 20 least one halogen atom; a C2-C6 alkenyl group optionally substituted with at least one halogen atom; or a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group 25 optionally substituted with at least one halogen atom, (5) a 69 Cl-C6 alkoxy group optionally substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least-one 5 halogen atom, (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally substituted with at least one halogen atom and (10) a C2-C6 alkoxycarbonyl group optionally substituted with at least one halogen atom, 10 R7 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R and R 9 are independently a hydrogen atom; a Cl-C6 alkyl group optionally substituted with at least one halogen atom; or a phenyl group optionally substituted with 1 to 5 independent 15 substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally 20 substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally substituted with at least one 25 halogen atom and (10) a C2-C6 alkoxycarbonyl group optionally 70 substituted with at least one halogen atom, Rio is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R" and R are independently a Cl-C6 alkyl group 5 optionally substitutedwith at least one halogen atom, J is a group represented by Jl or J2: (R 14a) P (R b )q Z -'Y a bLb J1 a J2 R a 413a (wherein Xa is CH or a nitrogen atom, Ya is CH, Za is CH or a nitrogen atom, Xb is CH or a nitrogen atom, yb is CH, and Zb is 10 CH or a nitrogen atom, R13a is a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 15 alkyl group; a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally 20 substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally 71 substituted with at least one halogen atom and (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom; or a 5- to 6-membered heteroaryl group optionally substituted with one or more independent substituents selected 5 from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, 10 R13b is a Cl-C6 alkyl group optionally substituted with at least, one halogen atom, R14a is a halogen atom; a cyano group; a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a Cl-C6 alkylthio group optionally substituted with at least one 15 halogen atom; a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom; a C1-C6 alkylsulfonyl group optionally substituted with at least one halogen atom; or a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group 20 consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a C1-C6 alkoxy group optionally substituted with at least one halogen atom, R14b is a Cl-C6 alkyl group optionally substituted with at 25 least one halogen atom; or a phenyl group optionally 72 substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 5 alkoxy group optionally substituted with at least one halogen atom, p is an integer of 0 to 2, q is 1, (provided that when p is 2, two Rl 4 a's may be the same or 10 different)), and ,A' and A 2 are an oxygen atom. Examples of the specificaspects of the present compound include the following "Aspects 1 to 32": "Aspect 1" 15 A compound of the formula (1-1): R14az Xa Nlb

R

4 4

R

4 b N 1 (-1)

R

80

R

4 c -NR 2 -NR3 M wherein R is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 20 R 2 is a hydrogen atom, or a Cl-C6 alkyl group optionally ,73 substituted with at least one halogen atom, R3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, 5 R 4 a is a hydrogen atom, a halogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, or a phenyl group optionally substituted with at least one halogen atom, 10 R 4, R 4 c and R are independently a hydrogen atom, a halogen atom,, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or R 4 b and R 4 c are bound to each other at their terminal ends to form a group:

-CR

41

=CR

42 -CR43=CR 44 15 (wherein R 41 , R 4 2 , R43 and R 44 are a hydrogen atom), M is R 5 , OR 6 , SR 7 , or NR 8 R' (wherein

R

5 is a hydrogen atom; a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a C3-C6 cycloalkyl 20 group; a phenyl group optionally substituted with one substituent selected from the group consisting of (1) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (2) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; a 5 to 6-membered heteroaryl group; 25 or a 3- to 8-membered non-aromatic heterocyclic group, .74

R

6 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, or a phenyl group,

R

7 is a Cl-C6 alkyl group optionally substituted with at' 5 least one halogen atom, Re and R 9 are independently a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a phenyl group, or Re and R 9 are taken together with the nitrogen atom to which they are bound to form a morpholino 10 group), Xa is a nitrogen atom, R 14 ay is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted 15 with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, or a phenyl group, Ri" is a hydrogen atom, 20 XIS is a nitrogen atom or CR 8 e (wherein R18* is a hydrogen atom or a halogen atom), and

R

18 a, R1 8 b, Riec and Rl 8 d are independently a hydrogen atom or a halogen atom. "Aspect 2" 25 A compound of the formula (1-1), wherein ,75 R is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R2 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, - ' 5 R 3 is a hydrogen atom, a C1-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, R4a is a hydrogen atom, a halogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 10 alkoxy group optionally substituted with at least one halogen atom,, or a phenyl group optionally substituted with at least one halogen atom, R b, R 4 e and R4d are independently a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally 15 substituted with at least one halogen atom, or R 4 b and R 4 c are bound to each other at their terminal ends to form a group; -CR 41 =CR2-CR 4=CR 44 (wherein R 4 1 , R 4 2 , R 4 3 and R44 are a hydrogen atom), M is R 5 , OR 6 , SR 7 , or NR R 9 20 (wherein R 5 is a hydrogen atom; a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a C3-C6 cycloalkyl group; a phenyl group optionally substituted with one substituent selected from the group consisting of (1) a C1-C6 alkyl group optionally substituted with at least one halogen 25 atom and (2) a Cl-C6 alkoxy group optionally substituted with 176 at least one halogen atom; a 5 to 6-membered heteroaryl group; or a 3- to 8-membered non-aromatic heterocyclic group, R is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally 5 substituted with at least one halogen atom, or a phenyl group, R is a C1-C6 alkyl group optionally substituted with at least one halogen atom,

R

8 and R 9 are independently a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 10 or a phenyl group, or R 8 and R 9 are taken together with the nitrogen atom to which they are bound to form,a morpholino group), Xa is CR" 4 ax (wherein R 14 1" is a hydrogen atom; a halogen atom; a cyano group; 15 a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a Cl-C6 alkylthio group optionally substituted with at least one halogen atom; or a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfonyl group optionally substituted with at least one 20 halogen atom, or a phenyl group),

R

14 ay is a hydrogen atom; a halogen atom; a cyano group; a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a Cl-C6 alkylthio group optionally substituted with at least one halogen atom; a Cl-C6 alkylsulfinyl group 25 optionally substituted with at least one halogen atom; a Cl-C6 77 alkylsulfonyl group optionally substituted with at least one halogen atom; or a phenyl group, R i4, is a hydrogen atom, xI is a nitrogen atom or CRe 5 (wherein R1* is a hydrogen atom or a halogen atom), and Ri1a, R1 8 b, Ri1c and Rl 8 d are independently a hydrogen atom or a halogen atom. "Aspect 3" A compound of the formula (1-1), wherein 10 Ri is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R2 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally 15 substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, R4a is a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

4 b is a hydrogen atom, 20 R 4 c is a hydrogen atom, a halogen atom, a cyano group, or a C1-C6 alkyl group optionally substituted with at least one halogen atom,

R

4 d is a hydrogen atom, a halogen atom, or a C1-C6 alkyl group optionally substituted with at least one halogen atom, 25 M is OR 6 78 (wherein R6 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom), Xa is a nitrogen atom, R1 4 ay is a hydrogen atom, a halogen atom, a Cl-C6 al-kyl' 5 group optionally substituted with at least one halogen atom, Ri4az is a hydrogen atom, X18 is a nitrogen atom, R ia is a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, and 10 R8b , R 18 c and R1 8 d are a hydrogen atom. "Aspect 4" A compound of the formula (1-1), wherein R1 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 15 R2 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, 20 R 4 , is a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

4 b is a hydrogen atom, Rac is a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one 25 halogen atom, .79 R4d is a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, M is OR 6 (wherein R 6 is a Cl-C6 alkyl group optionally substituted with 5 at least one halogen atom), Xa is CRl 4 ax , (wherein R 1 4,ax is a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom), 10 Raay is a hydrogen atom, a halogen atom, a Cl-C6 alkyl group. optionally substituted with at least one halogen atom, R4az is a hydrogen atom,, X18 is a nitrogen atom, Xl 8 a is a halogen atom, or a Cl-C6 alkyl group optionally 15 substituted with at least one halogen atom, and Ria , R18c and Rl 8 d are a hydrogen atom. "Aspect 5" A compound of the formula (1-1), wherein R1 is a hydrogen atom or a methyl group, 20 R2 is a hydrogen atom or a methyl group,

R

3 is a hydrogen atom, a methyl group, or a methoxycarbonyl group, R4a is a hydrogen atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, an ethyl group, a 25 trifluoromethyl group, a methoxy group, or a phenyl group, ,80

R

4 c is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, or a cyano group, R 4 and R4d are a hydrogen atom, a chlorine atom, or a methyl group, 5 M is OR 6 (wherein R 6 is a methyl group), X8 is a nitrogen atom,

R

14 ay is a hydrogen atom, a chlorine atom, a bromine atom, a cyano group, a methyl group, an isopropyl group, a 10 trifluoromethyl group, a methylthio group, a methylsulfinyl group,, a methylsulfonyl group, or a phenyl group, R14az is a hydrogen atom or a bromine atom, X18 is a nitrogen atom, Ri8' is a chlorine atom, and 15 Rib, Ric and Ri8d are a hydrogen atom. "Aspect 6" A compound of the formula (1-1), wherein Ri is a hydrogen atom or a methyl group, R2 is a hydrogen atom or a methyl group, 20 R 3 is a hydrogen atom, a methyl group, or a methoxycarbonyl group R 4 is a hydrogen atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, an ethyl group, a trifluoromethyl group, a methoxy group, or a phenyl group, 25 R 4 c is a hydrogen atom, a fluorine atom, a chlorine atom, .81 a bromine atom, an iodine atom, a methyl group, or a cyano group, R 4 and R4d are a hydrogen atom, a chlorine atom, or a methyl group, M is OR6 5 (wherein R 6 is a methyl group), Xa is CRi4ax (wherein Riaax is a hydrogen atom or a halogen atom), R14ay is a hydrogen atom, a chlorine atom, a bromine atom, a cyano group, a methyl group, an isopropypl group, a 10 trifluoromethyl group, a methylthio group, a methylsulfinyl group,, a methylsulfonyl group, or a phenyl group,

R

1 "4az is a hydrogen atom or a bromine atom, Xle is a nitrogen atom, R18' is a chlorine atom, and 15 R 18, R18c and Ri8d are a hydrogen atom. "Aspect 7" A compound of the formula (1-1), wherein R1 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 20 R2 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom.

R

3 is a hydrogen atom, a C1-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, 25 R4a is a hydrogen atom, a halogen atom, a Cl-C6 alkyl group ,82 optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, or a phenyl group optionally substituted with at least one halogen, atom, 5 R 4 b, Rae and R 4 d are independently a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or R 4 and R4 are bound to each other at their terminal ends to form a group: -CR 4

=CR

4 2

-CR

4 3

=CR

44 10 (wherein R , R 4 2 , R 43 and R 44 are a hydrogen atom), .M is OR6, SR7 or NR8R9 (wherein R 6 and R 7 are a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, 15 a C2-C6 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at least one halogen atom,

R

8 and R 9 are independently a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 20 a C2-C6 alkenyl group optionally substituted with at least one halogen atom, a C3-C6 alkynyl group optionally substituted with at least one halogen atom, or R8 and R 9 are taken together with the nitrogen atom to which they are bound to form a pyrroridin-1-yl group, a 25 piperidino group, a hexamethyleneimin-1-yl group, a 83 heptamethyleneimin-1-yl group, a morpholino group, a thiomorpholin-4-yl group, or a 4-phenylpiperazin-1-yl group), Xa is a nitrogen atom or CR1ax (wherein X 1 ax is a hydrogen atom, a halogen atom, a cyano group, 5 a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 alkylthio group optionally substituted with at least one halogen atom, or a C1-C6 alkylsulfinyl group optionally substituted with at least one halogen atom), R14ay is a hydrogen atom, a halogen atom, a cyano group, 10 a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 alkylthio group optionally substituted with at least one halogen atom, or a C1-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfonyl group optionally substituted with at least one 15 halogen atom, or a phenyl group, Rua, is a hydrogen atom, X18 is a nitrogen atom or a CRle (wherein R1e is a hydrogen atom or a halogen atom), and 18a 18b 18c 18d R R , R and R are independently a hydrogen atom 20 or a halogen atom. "Aspect 8" A compound of the formula (1-1), wherein Ri is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 25 R 2 is a hydrogen, or a Cl-C6 alkyl group optionally ,84 substituted with at least one halogen atom,

R

3 is a hydrogen, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, 5 R 4 ' is a hydrogen atom, a halogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 alkoxy group optionally substituted with at least one halogen atom, or a phenyl group optionally substituted with at least one halogen atom. 10 R 4 b, R 4 c and R 4 d are independently a hydrogen atom, a halogen atom,, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or R 4 and R 4 c are bound to each other at their terminal ends to form a group: -CR 4 =CR 4-CR 4=CR 15 (wherein R 41 , R 42 , R 43 and R 44 are a hydrogen atom), M is a hydrogen atom, Xa is a nitrogen atom or CR14", (wherein R14ax is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one 20 halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a C1-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfony group optionally 25 substituted with at least one halogen atom), ,85 R1 4 ay is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group 5 optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, or a phenyl group, R14az is a hydrogen atom, X18 is a nitrogen atom or CR18" 10 (wherein R Be is a hydrogen atom or a halogen atom), and R ia, R 8 b, R18c and R1 8 d are independently a hydrogen atom or a halogen atom. "Aspect 9" A compound of the formula (1-1), wherein 15 R1 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R2 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally 20 substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group,

R

4 a is a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R 4, R 4 c and RId are independently a hydrogen atom, a halogen 25 atom, a cyano group, or a Cl-C6 alkyl group optionally .86 substituted with at least one halogen atom, or R 4 b and R C are bound to each other at their terminal ends to form a group: -CR 41

=CR

4 2 -CR43=CR 44 (wherein R 41 , R 42 , R 43 and R44 are independently a hydrogen atom, 5 a halogen atom, a cyano group or a Cl-C6 alkyl group optionally substituted with at least one halogen atom), M is R 5 , OR6, SR or NR'R', (wherein R 5 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 10 R 6 and R 7 are a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, a C2-C6 alkynyl group optionally substituted with at least one halogen atom or a C3-C6 alkynyl group optionally substituted with at 15 least one halogen atom, R8 and R 9 are independently a hydrogen atom, a Cl-C6 alkyl group optionally substituted'with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, a C3-C6 alkynyl group optionally substituted with 20 at least one halogen atom, or R 8 and R 9 are taken together with the nitrogen atom to which they are bound to form a pyrrolidin-1-yl group, a piperidino group, a hexamethyleneimin-1-yl group, a heptamethyleneimin-1-yl group, a morpholino group or a 25 thiomorfolin-4-yl group), ,87 Xa is a nitrogen atom or CRL 4 ax (wherein R1 4 ax is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with a halogen atom, a Cl-C6 alkoxy group optionally substituted with a halogen atom, 5 a Cl-C6 alkylthio group optionally substituted with a halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with a halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with a halogen atom), R 14ay and R 1 4 az are independently a hydrogen atom, a halogen 10 atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at L5 least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, XIB is a nitrogen atom or CR'8e, (wherein R18* is a hydrogen atom, a halogen atom, or Cl-C6 alkyl group optionally substituted with at least one halogen atom), 20 and R 1a, R 1b, RiSC and R 1d are independently a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom. "Aspect 10" 25 A compound of the formula (1-1), wherein 88 R is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R2 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 5 R3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, 4a R is a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 10 R 4, R 4 c and R are independently a hydrogen atom, a halogen atom,, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or R 4 b and R 4 ' are bound to each other at their terminal ends to form a group: -CR 41

=CR

4 2

-CR

43 =CR 1 15 (wherein R 41 , R 42 , R 43 and R44 are independently a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least on'e halogen atom), M is R 5 , OR', SR' or NR 8

R

9 , (wherein R 5 is a hydrogen atom, or a Cl-C6 alkyl group 20 optionally substituted with at least one halogen atom,

R

6 and R 7 are a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen 25 atom, or a C3-C6 alkynyl group optionally substituted with at ,89 least one halogen atom., R' and R 9 are independently a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least- one 5 halogen atom, a C3-C6 alkynyl group optionally substituted with at least one halogen atom; or R 8 and R 9 are taken together with a nitrogen atom to which they are bound to represent a pyrrolidin-1-yl group, a piperidino group, a hexamethyleneimin-1-yl group, a 10 heptamethyleneimin-1-yl group, a morpholino or a thiomorpholin-4-yl group), Xa is a nitrogen atom, R"" and R'" are independently a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted 15 with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted'with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group 20 optionally substituted with at least one halogen atom, X 1 is a nitrogen atom or CR11", (wherein R 1 Se is a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom), and ia ibb 18d 25 R , R ,R1Oc and R are independently a hydrogen atom, .90 a halogen atom or a Cl-C6 alkyl group optionally substituted with at least one halogen atom. "Aspect 11" A compound of the formula (1-1), wherein 5 R1 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R2 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally 10 substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, R 4 is a halogen atom, or, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R b, R 4 and R4d are independently a hydrogen atom, a halogen 15 atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or R 4 b and R 4c are bound to each other at their terminal ends to for a group: -CR 41

=CR

42

-CR

4 3

=CR

44 (wherein R 41, R 42, R43 and R 44 are independently a hydrogen atom, 20 a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom), M is R5, OR6, SR or NR R, (wherein R 5 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 25 R 6 and R 7 are a Cl-C6 alkyl group optionally substituted 91 with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at 5 least one halogen atom, Re and R 9 are independently a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, a C3-C6 alkynyl group optionally substituted with 10 at least one halogen atom, ,or Re and R 9 are taken together with the nitrogen atom to which they are bound to forma pyrroridin-1-yl group, a piperidino group, a hexamethyleneimin-1-yl group, a heptamethyleneimin-1-yl group, a morpholino group or a 15 thiomorpholin-4-yl group), Xa is CR1 4 ax (wherein R 14 ax is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with 20 at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom), 25 R 14 ay and R1 4 az are independently a hydrogen atom, a halogen 92 atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, 5 a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, X1B is a nitrogen atom, or CRIG", (wherein R 1 * is a hydrogen atom, a halogen atom, or a C1-C6 alkyl 10 group optionally substituted with at least one halogen atom), and , Risa, R ib, Riec and R18d are independently a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom. 15 "Aspect 12" A compound of the formula (1-1), wherein Ri is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

2 is a hydrogen atom, or a Cl-C6 alkyl group optionally 20 substituted with at least one halogen atom,

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, R" is a halogen atom, or a Cl-C6 alkyl group optionally 25 substituted with at least one halogen atom, -93 R b, R4c and R are independently a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or R4b and R44 are bound to each other at their terminal 5 ends to form a group: '-CR 41

=CR

4 2

-CR

4 3 =CR 44 (wherein R 41 , R 42 , R 43 and R 44 are independently a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom), M is R, OR6, SR7 or NR8R9, 10 (wherein R 5 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R6 and R7 are a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, a C2-C6 15 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at least one halogen atom,

R

8 and R 9 are independently a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 20 a C2-C6 alkenyl group optionally substituted with at least one halogen atom, a C3-C6 alkynyl group optionally substituted with at least one halogen atom, or R 8 and R 9 are taken together with the nitrogen atom to which they are bound to form a pyrroridin-1-yl group, a 25 piperidino group, a hexamethyleneimin-1-yl group, a * 94 heptamethyleneimin-1-yl group, a morpholino group or a thiomorpholin-4-yl group), Xa is CR 4 ax (wherein R 1 4ax is a hydrogen atom, a halogen atom, a cyano group, 5 a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one 10 halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom), Ray and R"a are independently a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally 15 substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, 20 Xis is a nitrogen atom, or CRi ", (wherein Rise is a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom), and R 1a, IR b, R iC and R1 d are independently a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted 25 with at least one halogen atom.

-95 "Aspect 13" A compound of the formula (1-1), wherein Ri is a hydrogen atom, or a C1-C6 alkyl group optionally substituted with at least one halogen atom, 5 R 2 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least 'one halogen atom,

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, 10 R 4 a is a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R is a hydrogen atom, R 4 is a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one 15 halogen atom, R4d is a hydrogen atom, 6 M is OR

R

6 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 20 Xa is a nitrogen atom, Ruay is a hydrogen atom, a halogen atom, or aCl-C6 alkyl group optionally substituted with at least one halogen atom,

R

1 4 az is a hydrogen atom, Xle is a nitrogen atom, 25 Risa is a halogen atom, or a Cl-C6 alkyl group optionally 96 substituted with at least one halogen atom, and R8b , Ri"c, R Od are a hydrogen atom. "Aspect 14" A compound of the formula (1-1), wherein 5 R1 is a hydrogen atom, or a C1-C6 alkyl group optionally substituted with at least one halogen atom, R2 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R3 is a hydrogen atom, a Cl-C6 alkyl group optionally 10 substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group,

R

4 a is a hydrogen atom, a halogen atom or a C1-C6 alkyl group optionally substituted with at least one halogen atom, R 4 is a hydrogen atom, 15 R 4 C is a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R4d is a hydrogen atom, M is OR6, 20 R 6 is a C1-C6 alkyl group optionally substituted with at least one halogen atom, X' is a CRi 4 ax (wherein R 1 4ax represents a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one 25 halogen atom), *97 R1 4 ay is a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

14 ", is a hydrogen atom, X 18is a nitrogen atom, 5 Ria is a halogen atom, or a C1-C6 alkyl group optionally substituted with at least 'one halogen atom, and 18b 18c 18d R , R and R are a hydrogen atom. "Aspect 15" A compound of the formula (1-1), wherein 10 R is a hydrogen atom or a methyl group, ,R2 is a hydrogen atom or a methyl group,

R

3 is a hydrogen atom, a methyl group, or a methoxycarbonyl group, R4a is a chlorine atom, a bromine atom, an iodide atom, 15 or a methyl group,

R

4 c is a chlorine atom, a bromine atom, an iodine atom, a methyl group or a cyano group,

R

4 b and R 4 d are a hydrogen atom, M is a OR 6 20 (wherein R 6 is a methyl group), Xa is a nitrogen atom, R14ay is a chlorine atom, a bromine atom, or a trifluoromethyl group, R14az is a hydrogen atom, 25 X is a nitrogen atom, 98 Risa is a chlorine atom or a bromine atom, and R 18b, R8c and Ried are a hydrogen atom. "Aspect 16" A compound of the formula (1-1), wherein 5 Ri is a hydrogen atom or a methyl group, R2 is a hydrogen atom or a methyl group, . 3 is a hydrogen atom, a methyl group, or a methoxycarbonyl group,

R

4 a is a chlorine atom, a bromine atom, or an iodine atom, 10 or a methyl group,

,R

4 c is a chlorine atom, a bromine atom, an iodine atom, a methyl group or a cyano group, R 4 and R4d are a hydrogen atom, M is OR 6 15 (wherein R 6 is a methyl group), is CRinax (wherein Ri 4 ax is a hydrogen atom, a chlorine atom or a bromine atom), R14ay is a chlorine atom, a bromine atom or a trifuoromethyl 20 group, R 14az is a hydrogen atom, X18 is a nitrogen atom, Risa is a chlorine atom or a bromine atom, and R 18, R18C and R18d are a hydrogen atom. 25 "Aspect 17" 99 A compound of the formula (1-1), wherein R1 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R2 is a Cl-C6 alkyl group optionally substituted with at' 5 least one halogen atom',

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group,

R

4 a is a halogen atom, or a Cl-C6 alkyl group optionally 10 substituted with at least one halogen atom, R 4, R 4 c and R4d are independently a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or R4b and R 4 " are bound to each other at their terminal 15 ends to form a group: -CR 41

=CR

42

-CR

43 =CR 44 (wherein R 41, R 42, R43 and R44 are independently a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom), M is OR 6 , SR 7 or NRR 9 , 20 (wherein R6 and R 7 are a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally 25 substituted with at least one halogen atom, 100 Re and R', each, independently, are a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, a C3-C6 alkynyl group optionally 5 substituted with at least one halogen atom, or Re and R 9 are taken together with the nitrogen atom.to which they are bound to form a pyrrolidin-1-yl group, a piperidino group, a hexamethyleneimin-1-yl group, a heptamethyleneimin-1-yl group, a morpholino group, or a 10 thiomorpholino-4-yl group), Xa is a nitrogen atom or CRi4ax (wherein R14ax is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with 15 at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom), 20 R"'y and R1 4 aZ are independently a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, 25 a Cl-C6 alkylsulfinyl group optionally substituted with at ,101 least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, X 1 is a nitrogen atom, or CR18e (wherein Rise is a hydrogen atom, a halogen atom, or a Cl-C6 alkyl 5 group optionally substituted with at least one halogen atom), and Risa, R ib, Risc and R'd are independently a hydrogen atom, a halogen atomor a Cl-C6 alkyl group optionally substituted with at least one halogen atom. 10 "Aspect 18" A compound of the formula (1-1), wherein Ri is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R2 is a hydrogen atom, or a Cl-C6 alkyl group optionally 15 substituted with at least one halogen atom, R3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, R 4 is a halogen atom, or a Cl-C6 alkyl group optionally 20 substituted with at least one halogen atom,

R

4 b, R 4 c and R 4 are independently a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or R 4 b and R 4 c are bound at end to be -CR 41

=CR

4 2

-CR

43 =CR 44 25 (wherein R 41 , R 42 , R 43 , and R 4 4 , each, independently, are a 102 hydrogen atom, a halogen atom, a cyano group, or a C1,-C6 alkyl group optionally substituted with at least one halogen atom, M is a hydrogen atom, Xa is a nitrogen atom or CR1 4 ax 5 (wherein R1 4 ax is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a C1-C6 10 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom), R ay and R 1az, each, ,independently, are a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally 15 substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 20 alkylsulfonyl group optionally substituted with at least one halogen atom, X 1 is a nitrogen atom or CRie, (wherein R* 8 e is a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom), 25 and 103 Ria , R 18, Risc and R 1d are independently a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom. "Aspect 19" 5 A compound of the' formula (1-1), wherein R is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted 'with at least one halogen atom, R2 is a hydrogen atom, or a C1-C6 alkyl group optionally substituted with at least one halogen atom, 10 R 3 is a hydrogen atom, a Cl-C6 alkyl group optionally subst,ituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, R4a is a hydrogen atom, a halogen atom, a cyano group, or a nitro group or a Cl-C6 alkyl group optionally substituted with 15 at least one halogen atom, R4b and R 4 - are bound to each other at their terminal ends to form a group: -CR =CR 4-CR 43=CR 44 (wherein R 41 , R 42 , R 43 and R 44 are independently a hydrogen atom, a halogen atom, a cyano group, a nitro group, or a Cl-C6 alkyl 20 group optionally substituted with at least one halogen atom), R4d is a hydrogen atom, a halogen atom, a cyano group, a nitro group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, M is R 5 , OR 6 , SR' or NR 8

R

9 , 25 (wherein R 5 is a hydrogen atom, a Cl-C6 alkyl group optionally 104 substituted with at least one halogen atom, or a C3-C6 cycloalkyl group,

R

6 and R 7 are a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group 5 optionally substituted 'with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at least one halogen atom,

R

8 and R 9 are independently a hydrogen atom, a Cl-C6 alkyl 10 group optionally substituted with at least one halogen atom, a C2-,C6 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at least one halogen atom, or Re and R 9 are taken together with the nitrogen atom to 15 which they are bound to form a pyrroridin-1-yl group, a piperidino group, a hexamethyleneimin-1-yl group, a heptamethyleneimin-1-yl group, a morpholino group, a thiomorphorin-4-yl group, or a 4-methylpiperazin-1-yl group), Xa is a nitrogen atom or CR14a, 20 R 14ax, R1 4 ay and Ri 4az are independently a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one 25 halogen atom, a Cl-C6 alkylsulfinyl group optionally ,105 substituted with at least one halogen atom, or a Cl-C6 alkyl sulfonyl group optionally substituted with at least one halogen atom, Xle is a nitrogen atom, or a CRi", and 5 Ris, Risb, RSC, R 1 84 and Ris" are independently a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted 'with at least one halogen atom. "Aspect 20" A compound of the formula (1-1), wherein 10 R' is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 2 R is a hydrogen atom, or, a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally 15 substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, R4a is a hydrogen atom o'r a halogen atom, R4b and R 4 c are bound to each other at their terminal ends to form a group: -CR 41

=CR

42

-CR

43

=CR

44 20 (wherein R 41 , R 42 , R 43 and R 44 are independently a hydrogen atom, or a halogen atom), R4d is a hydrogen atom, M is R 5 , OR 6 , SR" or NR 8 R, (wherein R5 is a hydrogen atom, a Cl-C6 alkyl group optionally 25 substituted with at least one halogen atom, or a C3-C6 106 cycloalkyl group, R6 and R are a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, a C2-C6 5 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at least one halogen atom, Re and R 9 are independently a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 10 a C2-C6 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at least one halogen atom, or Re and R 9 are taken together with the nitrogen atom to which they are bound to form a pyrroridin-1-yl group, a 15 piperidino group, a hexamethyleneimin-1-yl group, a heptamethyleneimin-1-yl group, a morpholino group, a thiomorphorin-4-yl group, or a 4-methylpiperazin-1-yl group), Xa is a nitrogen atom or CRi"an R 14ax, R1 4 ay and R14az are independently a hydrogen atom, a 20 halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally 25 substituted with at least one halogen atom, or a Cl-C6 ,107 alkylsulfonyl group optionally substituted with at least one halogen atom, X 18is a nitrogen atom, or a CRle, and Rsa , RT8b, R 18 e, Ri8d and Rle" are independently a hydrogen 5 atom, a halogen atom,' or a C1-C6 alkyl group optionally substituted with at least one halogen atom. "Aspect 21" A compound represented by the formula (1-2): ' R14ay XaR1a NH (1-2)

R

4 C C-NR 2

-NR

3

-COOR

00 10 wherein,

R

2 represents a hydrogen atom or a C1-C6 alkyl group,

R

3 represents a hydrogen atom' or a methyl group,

R

4 a represents a halogen atom or a methyl group,

R

4 c represents a halogen atom, 15 RiMay represents a halogen atom or a trifluoromethyl group, Xa represents a nitrogen atom or CH, Risa represents a halogen atom, and R1 00 represents a Cl-C6 alkyl group. "Aspect 22" 108 A compound of the formula (1-2), wherein

R

2 is a Cl-C6 alkyl group, R3 is a hydrogen atom or a methyl group, R is a halogen atom, or a methyl group, 5 R 4 c is a halogen atom, Ri 4 ay is a halogen atom or a trifluoromethyl group, X8 is a nitrogen atom or CH, and Ri 8 ' is a halogen atom. "Aspect 23" 10 A compound represented by the formula (1-3): R1 4 ay Xa R 18a R 0O NH (1-3)

-NR

2

-NR

3

-COOR

0 0 wherein R2 represents a hydrogen atom or a Cl-C6 alkyl group, R3 represents a hydrogen atom or a methyl group, 15 R4a represents a halogen atom or a methyl group, R1 4 "y represents a halogen atom or a trifluoromethyl group, Xa represents a nitrogen atom or CH, Risa represents a halogen atom, and R1 00 represents a Cl-C6 alkyl group.

109 "Aspect 24" A compound of the formula (1-1), wherein R1 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 5 R2 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least 'one halogen atom,

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, 10 R4a is a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R I is a hydrogen atom, R 4 is a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one 15 halogen atom,

R

4 d is a hydrogen atom, M is OR6 (wherein R 6 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally 20 substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at least one halogen atom), Xa is a nitrogen atom or CR14ax 25 (wherein R 14 oa is a hydrogen atom, a halogen atom, a cyano group, 110 a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 5 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 a'lkylsulfonyl group optionally substituted 'with at least one halogen atom), R14ay is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one 10 halogen atom, a C1-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally 15 substituted with at least one halogen atom, Rl1a" is a hydrogen atom, Xle is a nitrogen atom Risa is a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, and 20 Rlb , RieC, Ried are a hydrogen atom. "Aspect 25" A compound of the formula (1-1), wherein RI is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 25 R 2 is a hydrogen atom, or a C1-C6 alkyl group optionally -111 substituted with at least one halogen atom,

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, or, a C2-C6 alkoxycarbonyl group, 5 R 4 a is a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R is a hydrogen atom, R 4C is a hydrogen atom, a halogen atom, a cyano group, or a C1-C6 alkyl group optionally substituted with at least one 10 halogen atom, ,R"4d is a hydrogen atom, M is OR6, (wherein R 6 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group 15 optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at least one halogen atom), X6 is a nitrogen atom, 20 R 1 4ay is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a C1-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 25 alkylsulfinyl group optionally substituted with at least one - 112 halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, R1 4 az is a hydrogen atom,

X

18 is .a nitrogen atom, 5 Risa is a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least 'one halogen atom, and R 18b , R 1 R18d are a hydrogen atom. "Aspect 26" , A compound of the formula (1-1), wherein 10 R 1 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R3 is a hydrogen atom, a Cl-C6 alkyl group optionally 15 substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, R4a is a halogen atom or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R4b is a hydrogen atom, 20 R 4 C is a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

4 d is a hydrogen atom, M is OR , 25 (wherein R 6 is a C1-C6 alkyl group optionally substituted .113 with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at' 5 least one halogen atom), Xa is a CR 4 ,a (wherein R 14 a is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 alkoxy group optionally substituted with 10 at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom), 15 R ,ay is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 20 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom,

R

14 az is a hydrogen atom, X18 is a nitrogen atom, 25 Ri8a is a halogen atom, or a Cl-C6 alkyl group optionally 114 substituted with at least one halogen atom, and R 18b , Rec and Rl1d are a hydrogen atom. "Aspect 27" A compound of the formula (1-1), wherein 5 Ri is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R2 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

3 is a hydrogen atom, a C1-C6 alkyl group optionally 10 substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group, R4a is a halogen atom, or- a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

4 b is a hydrogen atom, 15 R 4 c is a hydrogen atom, a halogen atom, a cyano group, or a C1-C6 alkyl group optionally substituted with at least one halogen atom, R4d is a hydrogen atom, M is OR6, 20 (wherein R6 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at least 25 one halogen atom), ,115 Xa is a nitrogen atom or CRi"ax (wherein R 1 4ax is a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with 5 at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom), 10 R 14 ay is a hydrogen atom, a halogen atom, a cyano group, a Cl-,C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 15 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, R1 4 az is a hydrogen atom, X18 is a nitrogen atom, 20 Ri1a is a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, and Rlb , Risc, Rl1d are a hydrogen atom. "Aspect 28" A compound of the formula (1-1), wherein 25 R is a hydrogen atom, or a Cl-C6 alkyl group optionally .116 substituted with at least one halogen atom, R2 is a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

3 is a hydrogen atom, a Cl-C6 alkyl group optionally 5 substituted with at least one halogen atom, or a C2-C6 alkoxycarbonyl group,

R

4 a is a halogen atom, a cyano group, a nitro group, or a C1-C6 alkyl group optionally substituted with at least one halogen atom, 10 Rab and R 4 C are bound to each other at their terminal ends to form a group: -CR 41

=CR

42

-CR

43

=CR

44 (wherein R 41 , R 42 , R43 and R 44 are independently a hydrogen atom, a halogen atom, a cyano group, a nitro group, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom), 15 R4d is a hydrogen atom, M is OR 6 , (wherein R 6 is a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C3-C6 alkoxyalkyl group optionally substituted with at least one halogen atom, a C2-C6 alkenyl 20 group optionally substituted with at least one halogen atom, or a C3-C6 alkynyl group optionally substituted with at least one halogen atom), Xa is a nitrogen atom or CR1 4 ax (wherein R14ax is a hydrogen atom, a halogen atom, a cyano group, 25 a Cl-C6 alkyl group optionally substituted with at least one 117 halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least ond 5 halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom), RiPay is' a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with 10 at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, 15 R1 4 az is a hydrogen atom, X18 is a nitrogen atom, R18a is a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, and Rlb , R18c, Rlad are a hydrogen atom. 20 "Aspect 29" A compound represented by the formula (1-2), wherein R2 represents a hydrogen atom or a Cl-C6 alkyl group, R3 represents a hydrogen atom or a Cl-C6 alkyl group, R4a represents a halogen atom or a methyl group, 25 R 4 c represents a halogen atom, 118 R 14ay represents a halogen atom or a trifluoromethyl group, Xa represents a nitrogen atom or CRl 4 ax (wherein Ru 4 ax is a hydrogen atom or a halogen atom), Risa represents a halogen atom, and 5 R 100 represents a Cl-C6 alkyl group. "Aspect 30" A compound of the formula (1-2), wherein

R

2 is a Cl-C6 alkyl group, R3 is a hydrogen atom or a Cl-C6 alkyl group, 10 R4a is a halogen atom, or a methyl group, 4" is a halogen atom, Rl 4 ay is a halogen atom or a trifluoromethyl group, Xa is a nitrogen atom or CRl 4 ax (wherein R 1 4 ax is a hydrogen atom or a halogen atom), 15 Risa is a halogen atom, and R1 00 is a C1-C6 alkyl group. "Aspect 31" A compound of the formula (1-2), wherein R2 is a C1-C6 alkyl group, 20 R3 is a Cl-C6 alkyl group,

R

4 a is a halogen atom, or a methyl group,

R

4 c is a halogen atom,

R

14 ay is a halogen atom or a trifluoromethyl group, Xa is a nitrogen atom or CRl 4 ax (wherein R'a' represents a 25 hydrogen atom or a halogen atom), -119 Ria is a halogen atom, and R100 is a C1-C6 alkyl group. "Aspect 32" A compound represented by the formula (1-3), wherein 5 R 2 represents a hydrogen atom or a Cl-C6 alkyl group,

R

3 represents a hydrogen atom or a Cl-C6 alkyl group, R4a represents a halogen atom or a methyl group, Ri4ay represents a halogen atom or a trifluoromethyl group, Xa represents a nitrogen atom or CR1 4 ax (wherein Ri 4 ax 10 represents a hydrogen atom or a halogen atom), ,Ri1a represents a halogen atom, and

R

100 represents a Cl-C6 alkyl group. Hereinafter, a process for producing the present compound will be explained. 15 The present compound can be produced, for example, by the following Process A-1 to Process C-1. Process A-1 Among the present compounds, a compound represented by the formula (1-1): 1 1 N-C-J oc ~ (1-i) (R 4)

-NR

2 -NR3_., 112 20 A wherein R1, R 2, R 3, R 4, A , A 2, J and n are as defined above, Q' represents a group selected from the group consisting of Q1 to 120 Q6 (provided that the compound wherein Q' is Q4, and Re and R 9 are a hydrogen atom is excluded) (hereinafter, referred to as the compound (1-i)) can be produced by reacting a compound representedby the formula (2): 5 N-C-J 4 _r (2) (R4)

-NR

2

-NR

3 -H A2 wherein R , R 2 , R 3 , R 4 , Al, A 2 , J and n are as defined above (hereinafter, referred to as the compound (2) ), and a compound represented by the formula (3): 10 L--Q' (3) wherein Q' is as defined above, and L 1 represents a halogen atom or a Q'-0-group (provided that the case where Q' is Q4, and Re and R 9 are a hydrogen atom is excluded) (hereinafter, referred to as the compound (3)). 15 The reaction is performed in the presence or theabsence of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, 20 carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile and the like, aprotic ,121 polar solvents such as N,N-dimethylformamide, N-methlpyrrolidone, 1,3-dimethyl-2-imidadzolidinone, dimethyl sulfoxide, and the like, and a mixture thereof. The amount of the compound (3) to be used in the reaction' 5 is usually 1 to 2 mols per 1 mol of the compound (2). The reaction is performed in the presence of a base, if necessary. Examples of the base include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2,6-lutidine, 1,8-diazabicyclo[5,4,0]7-undecene (DBU), 10 1,5-diazabicyclo[4,3,0]5-nonene (DBN), and the like, tertiary amine's such as triethylamine, N,N-diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like. The amount of the base when the reaction is performed in the presence of the base is usually 15 1 to 2 mols per 1 mol of the compound (2), while the base may be used in an excess amount in case that the base used is liquid under the reaction conditions such as pyridine, and the like. The reaction temperature is usually in a range of 0 to 100*C, and the reaction time is usually in a range of 0.1 to 20 24 hours. After completion of the reaction, the compound (1-1) can be isolated by pouring the reaction mixture into water and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound 25 (1-1) may be further purified by recrystallization, 122 chromatography, or the like. Process A-2 Among the present compounds, a compound represented by the formula (1-11): 5

R

1 1 N-C-J (R4 )nI ( ~)

-NR

2 -- NR 3 -C-NHR a 11 2 1134 1 2 3 4 1 2 3 wherein R1, R 2 R , R , A , A , A 34 , J and n are as defined above, and Rea represents a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a C2-C6 alkoxyalkyl group 10 optionally substituted with at least one halogen atom; a C2-C6 alkenyl group optionally substituted with at least one halogen atom; a C3-C6 alkynyl group optionally substituted with at least one halogen atom; a C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected 15 from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group; a phenyl group optionally substituted with a 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom (2) a cyano group, (3) a nitro group, (4) a C1-C6 alkyl group optionally substituted with at least one 20 halogen atom, (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a 123 Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, (9) a C2-C6 dialkylamino group optionally substituted with at least one 5 halogen atom and (10) a C2-C6 alkoxycarbonyl group optionally substituted with at least one halogen atom; a 5- to 6-membered heteroaryl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 10 alkyl group optionally substituted with at least one halogen atomand (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; or-a C7-C9 phenylaklyl group whose benzene ring moiety may be substituted with 1 to 5 independent substituents selected from the group consisting of (1) a 15 halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom (hereinafter, referred to as the compound (1-u1) ) can be produced by reacting the compound (2) 20 with a compound represented by the formula (4):

A

34 =C==N-RBa (4) wherein A 34 and R8a are as defined above (hereinafter, referred to as the compound (4)). 25 The reaction is performed in the presence or the absence 124 of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform,' 5 carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, 10 dimethyl sulfoxide, and the like, and a mixture thereof. The amount of the compound (4) used in the reaction is usually 1 to 2 mols per 1 mol of the compound (2). The reaction temperature is usually in a range of 0 to 100*C, and the reaction time is a usually a range of 0.1 to 24 15 hours. After completion of the reaction, the compound (1-13) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound 20 (1-11) may be further purified by recrystallization, chromatography, or the like. Process A-3 Among the present compounds, a compound represented by the formula (1-111): 125 R N--C-J (R4)r I ( 1-m1 ) -NR2-NR3-C---NH 2 112 1134 wherein R 1 , R 2 , R 3 , R 4 , A 1 ' A 2 , A 34 , J and n are as defined above (hereinafter, referred to as the compound (I-iii)) can be produced by reacting the compound (2) and a cyanate or a 5 thiocyanate. The reaction is performed in the presence of a solvent. Examples of the solvent used in the reaction include acids such as organic acids such as acetic acids, and the like and mineral acids such as hydrochloric acid, and the like, as well as a 10 mixture of these acids and water, chloroform, or the like. The amount of the cyanate or the thiocyanate used in the reaction is usually 1 to 2 mols per 1 mol of the compound (2) . The reaction temperature is usually in a range of 0 to 100*C, and the reaction time is usually in a range of 0.1 to 15 24 hours. Examples of the cyanate or the thiocyanate include potassium cyanate, sodium cyanate, ammonium cyanate, potassium thiocyanate, sodium thiocyanate and ammonium thiocyanate. After completion of the reaction, the compound (I-iii) can 20 be isolated by pouring the reaction mixture into water and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated Compound 126 (I-iii) may be further purified by recrystallization, chromatography, or the like. Process B-1 The present compound can be produced by reacting a 5 compound represented by the formula (6): R4 N--H (R) (6) C-NR 2-NR3 A wherein R', R 2 , R 3 , R , A 2 , Q and n are as defined above (hereinafter, referred to as Compound (6) ) and a compound represented by the formula (7):

L

2 -C-J (7) 10 A wherein A' and J are as define above, and L 2 represents a halogen atom (hereinafter, referred to as the compound (7)). The reaction is performed in the presence or the absence of a solvent. Examples of the solvent used in the reaction 15 include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and 20 the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, ,127 N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof. The amount of the compound (7) used in the reaction is usually 1 to 2 mols per 1 mol of the compound (6). 5 The reaction is performed in the presence of a base, if necessary. Examples of the base include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2,6-lutidine, 1,8-diazabicyclo[5,4,0]7-undecene (DBU), 1,5-diazadicyclo[4,3,0]5-nonene (DBN), and the like, tertiary 10 amines such as triethylamine, N,N-diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like. , The amount of the base when the reaction is performed in the presence of the base is usually 1 to 2 mole per 1 mol of the compound (6), while the base may 15 be used in an excess amount in case that the base used is liquid under the reaction conditions such as pyridine, and the like. The reaction temperature is usually in a range of 0 to 100 0 C, and the reaction time is usually in a range of 0.1 to 24 hours. 20 After completion of the reaction, the present compound can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitation by filtration. The isolated present compound may be further purified by recrystallization, 25 chromatography, or the like.

,128 Process B-2 Among the present compounds, a compound represented by the formula (I-iv):

R

' 0 N-C-J (1-iv) ( 4) -I -NR2-NR 3_Q 112 A 51 2 3 4 2 5 wherein R1, R , R , R , A2, J, Q and n are as defined above (hereinafter referred to as the compound (I-iv) ) can be produced by reacting the compound (6) and a compound represented by the formula (8): HO-C-J (8) 0 10 wherein J is as defined above (hereinafter, referred to as the compound (8)) in the presence of a dehydrating agent. The reaction is performed in the presence or the absence of a solvent. Examples of the'solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, 15 tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic 20 polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, 129 dimethyl sulfoxide, and the like, and a mixture thereof. The amount of the compound (8) used in the reaction is usually 1 to 2 mols per 1 mol of the compound (6). Examples of the dehydrating agent to be used in the' 5 reaction include carbodiimides such as dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSC), and the like. The amount of the dehydrating agent to be used is usually 1 to 2 mols per 1 mol of the compound (6) . 10 The reaction temperature is usually in a range of 0 to 100 0 C, and the reaction time is usually in a range of 0.1 to 24 hours. After completion of the reaction, the compound (I-iv) can be isolated by pouring the reaction mixture into water, and 15 extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (1-iv) may be further purified by recrystallization, chromatography, or the like. Process C-1 20 Among the present compounds, a compound represented by the formula (1-v): H 0 '-C-J (R4) -NR 2

-NR

3 II

O

.130 2 3 4 wherein R , R , R 4 , J, Q and n are as defined above (hereinafter, referred to as the compound (1-v)) can be produced by reacting a compound .represented by the formula (9): N J

(R

4 ) 0 (9) 0 5 wherein R 4 , J and n are as defined above (hereinafter, referred to as the compound (9) ) and a compound represented by the formula (10): H-N-N-Q L2 3 (10) wherein R 2, R3 and Q are as defined above (hereinafter, referred 10 to as the compound (10)). The reaction is performed in the presence or the absence of a solvent. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, 15 halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, 20 N-methylpyrrolidone, 1, 3-dimethyl-2-imidaozolidinone, dimethyl sulfoxide, and the like, and a mixture thereof. The amount of the compound (10) to be used in the reaction .131 is usually 1 to 20 mols per 1 mol of the compound (9). The reaction temperature is usually in a range of 0 to 100 0 C, and the reaction time is usually in a range of 0.1 to 48 hours. 5 After completion of the reaction, the compound (1-v) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (1-v) may be further purified by recrystallization, 10 chromatography, or the like. Proce,ss C-2 Among the present compounds, a compound represented by the formula (1-vi): S(1-vi)

-NR

2

-NR

3 -Q 0 15 wherein R 2 , R 3 , R 4 , A', J, Q and n are as defined above, Ri-a represents a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a C2-C6 cyanoalkyl group; a C2-C6 alkoxyalkyl group optionally substituted with at least one halogen atom; a C2-C6 alkenyl group optionally substituted with 20 at least one halogen atom; a C3-C6 alkynyl group optionally substituted with at least one halogen atom; or a C7-C9 phenylalkyl group in which a benzene ring part may be 132 substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6' 5 alkoxy group optionally substituted with at least one halogen atom (hereinafter, referred to as the compound (1-vi)) can be produced by reacting a compound represented by the formula (11) : R1-a 1 (R 4)n 0 10 wherein Ri-a, R 4 , Al, J and n are as defined above, and L 3 represents a halogen atom (hereinafter, referred to as the compound (11)) and the compound (10). The reaction is performed in the presence or the absence of a solvent. Examples of the solvent to be used in the reaction 15 include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichlorethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and 20 the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-diethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, ,133 , dimethyl sulfoxide, and the like, and a mixture thereof. The amount of the compound (10) to be used in the reaction is usually 1 to 2 mols per 1 mol of the compound (11). The reaction is performed in the presence of a base, if' 5 necessary. Examples of the base include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2,6-lutidine, 1,8-diazabicyclo[5,4,0)7-undecene (DBU), 1, 5-diazabicyclo[4, 3, 0J5-nonene (DBN) , and the like, tertiary amines such as triethylamine, N,N-diisopropylethylamine, and 10 the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like. The amount of the base to be used when the reaction is performed in the presence of the base is usually 1 to 2 mols per 1 mol of the compound (11) , while the base may be used in an excess amount in the case that the base 15 used is liquid under the reaction conditions such as pyridine and the like. The reaction temperature is usually in a range of 0 to 100 0 C, and the reaction time is usually in a range of 0.1 to 24 hours. 20 After completion of the reaction, the compound (1-vi) can be isolated after pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (1-vi) may be further purified by recrystallization, 25 chromatography or the like.

134 Process C-3 The compound (1-vi) can also be produced by reacting a compound represented by the formula (12): R1- 1L (R 4) n(12) -&OH 5 A wherein R 4 , Rl-a' A', J and n are as defined above (hereinafter, referred to as Compound (12)) and the compound (10) in the presence of a dehydrating agent. The reaction is performed in the presence or the absence 10 of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichlroethane, chlorobenzene, and 15 the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof. 20 The amount of the compound (10) used in the reaction is usually 1 to 2 mols per 1 mol of the compound (12). Examples of the dehydrating agent used in the reaction ,135 include carbodiimides such as dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (WSC), and the like. The amount of the dehydrating agent to be used is usually 1 to 2 mols per 1 mol of the compound (12). 5 The reaction temperature is usually in a range of 0 to 100"C, and the reaction time is usually in a range of 0.1 to 24 hours. After completion of the reaction, the compound (1-vi) can be isolated by pouring the reaction mixture into water and 10 extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (1-vi) may be further purified by recrystallization, chromatography, or the like. Then, a process for producing intermediates for producing 15 the present compound will be explained. Reference Process 1 Among the compound (2), a compound represented by the formula (2-1): H 0 N-C-J (R(2-i) C-NR2-N R 3 -H I I 0 20 wherein R 2 , R 3 , R 4 , J and n are as defined above (hereinafter, referred to as the compound (2-1)) can be produced by reacting the compound (9) and a compound represented by the formula (13) ,136 H-N-N-H 2 13 (13) wherein R 2 and R 3 are as defined above (hereinafter, referred to as the compound (13)). The reaction is performed in the presence or the absence 5 of a solvent. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene and 10 the like, hydrocarbons such as toluene, benzene, xylene and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and the like, alcohols such as methanol, 15 ethanol, 2-propanol, and the like, and a mixture thereof. The amount of the compound (13) to be used in the reaction is usually 1 to 5 mols per 1 mol of the compound (9). The reaction temperature is usually in a range of -50 to 100*C, and the reaction time is usually in a range of 0.1 to 20 24 hours. After completion of the reaction, the compound (2-1) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound ,137 (2-i) may be further purified by recrystallization, chromatography, or the like. Reference Process 2 Among the compound (2) , a compound represented by the' 5 formula (2-11): H S N-C-J (R 4) ( 2-u) C-NR 2-NR(-H S 2 3 4 wherein R2, R , R 4 , J and n are as defined above (hereinafter, referred to as Compound (2-11) ) can be produced by reacting a compound represented by the formula (14): N J (R 4) (14) 10 S wherein R 4 , J and n are as defined above (hereinafter, referred to as the compound (14)) and the compound (13). The reaction is performed in the presence or the absence of a solvent. Examples of the solvent to be used in the reaction 15 include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene and the like, hydrocarbons such as toluene, benzene, xylene, and 20 the like, nitriles such as acetonitrile, and the like, aprotic 138 polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and the like, alcohols such as methanol, ethanol, 2-propanol, and the like, and a mixture thereof. 5 The amount of the compound (13) to be used in the reaction is usually 1 to 5 mols per 1 mol of the compound (14). The reaction temperature is usually in a range of -50 to 100 0 C, and the reaction time is usually in a range of 0.1 to 24 hours. 10 After completion of the reaction, the compound (2-11) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (2-11) may be further purified by recrystallization, 15 chromatography, or the like. Reference Process 3 Among the compound (2), a compound represented by the formula (2-iii): -8 1 N-C-J

(R

4 )_ _(2-m)

-NR

2

-NR

3 -H 20 wherein Rla, R 2 , R 3 , R 4 , Al, J and n are as defined above (hereinafter, referred to as the compound (2-iii)) can be produced by reacting the compound (11) and the compound (13) .

.139 The reaction is performed in the presence or the absence of a solvent. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, 5 halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, 10 N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof. The amount of Compound (13) used in the reaction is usually 2 to 10 mols per 1 mol of the compound (11). The reaction temperature is usually in a range of -50 to 15 100 0 C, and the reaction time is in a range of 0.1 to 24 hours. After completion of the reaction, the compound (2-111) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound 20 (2-111) may be further purified by recrystallization, chromatography, or the like. Reference Process 4 The compound (9) can be produced by reacting a compound represented by the formula (16). 25 ,140 H N (R4) n (16) -0 wherein R 4 and n are as defined above (hereinafter, referred to as the compound (16)) and a compound represented by the formula (7'): 5 11 (7') 0 wherein J and L2 are as defined above (hereinafter, referred to as Compound (7')). The reaction is performed in the presence or the absence 10 of a solvent in the presence of a base. Examples of the solvent to be used in the reaction include ethers such as 1, 4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 15 chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and the 20 like, and a mixture thereof. The amount of the compound (7') used in the reaction is usually 0.5 to 2 mols per 1 mol of the compound (16).

,141 Examples of the base to be used in the reaction include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2, 6-lutidine, 1,8-diazabicyclo[5,4,0]7-undecene(DBU), 5 1,5-diazabicyclo[4,3,0]f5-nonene (DBN), and the like, tertiary amines such as triethylamine, N, N-diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like. The amount of the base to be used is usually 1 to 2 mols per 1 mol of the compound (16), while 10 the base may be used in an excess amount in case that the base is liquid under the reaction conditions such as pyridine, and the like. The reaction temperature is usually in a range of 50 to 150 0 C, and the reaction time is usually in a range of 1 to 24 15 hours. After completion of the reaction, the compound (9) can be isolated by pouring the reaction mixture into water, and extracting the mixture with an organic solvent, or collecting a deposited precipitates by filtration. The isolated compound 20 (9) may be further purified by recrystallization, chromatography, or the like. Reference Process 5 The compound (9) can be produced by reacting a compound represented by the formula (17): ,142

NH

2 (R 4)" (7 arH wherein R 4 and n are as defined above (hereinafter, referred to as Compound (17)) and the compound (7'). The reaction is performed in the presence or the absence 5 of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, and 10 the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1, 3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof. 15 The process comprises the following step 5-1 and step 5-2. Step 5-1 This step is performed by reacting the compound (17) and the compound (7') in the presence of a base. The amount of the compound (7') to be used in this step 20 is usually 1 to 2 mols per 1 mol of the compound (17). Examples of the base include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2,6-lutidine, 1, 8-diazabicyclo[5, 4 , O)7-undecene

(DBU),

,143 , 1,5-diazabicyclo[4,3,0]5-nonene (DBN), and the like, tertiary amines such as triethylamine, N,N-diisopropylethylamine, and the like, and inorganic bases such as potassium carbonate, sodium hydride, and the like. The amount of the base to be used 5 is usually 1 to 2 mols per 1 mol of the compound (17). The reaction temperature of this step is usually in a range of 0 to 50 0 C, and the reaction time is usually in a range of 0.1 to 24 hours. After completion of this step, usually, the reaction 10 mixture is used as it is in the next step 5-2. Step 5-2 This step is performed by reacting the reaction mixture in the step 5-1 and a sulfonyl halide in the presence of a base. Examples of the sulfonyl halide used in this step include 15 methanesulfonyl chloride, p-toluenesulfonyl chloride, and trifluoromethanesulfonyl chloride. The amount of the sulfonyl halide to be used in this step is usually 1 to 2 mols per 1 mol of the compound (17) used in the step 5-1. Examples of the base include the same bases as those 20 described with respect to the step 5-1. The amount of the base is usually 2 to 4 mols per 1 mol of the compound (17) used in the step 5-1. The reaction temperature of this step is usually in a range of 0 to 50*C, and the reaction time is usually in a range of 25 0.1 to 24 hours.

,144 After completion of this step, the compound (9) can be isolated by pouring the reaction mixture into water, followed by conventional extraction with an organic solvent. The isolated compound (9) may be further purified by, 5 recrystallization, chromatography, or the like. Reference Process 6 The compound (14) can be produced by reacting the compound (9) with a thiocarbonylation agent. The reaction is performed in the presence or the absence 10 of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, diglyme, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, 15 chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, pyridines such as pyridine, picoline, lutidine, and the like, and a mixture thereof. Examples of the thiocarbonylation agent to be used in the 20 reaction include diphosphorus pentasulfide, a Lawesson' s reagent (2, 4-bis- (4-methoxyphenyl) -1, 3-dithia-2, 4-diphosphetane 2,4-disulfide), and the like. The amount of the thiocarbonylation agent to be used in 25 the reaction is usually 1 to 3 mols per 1 mol of the compound 145 (9). The reaction temperature is usually in a range of 0"C to 200 0 C, and the reaction time is usually in a range of 1 to 24 hours. 5 After completion of the reaction, the compound (14) can be isolated by collecting a precipitate deposited in the reaction mixture by filtration, or extracting the reaction mixture with an organic solvent. The isolated compound (14) may be further purified by recrystallization, chromatography, 10 or the like. Reference Process 7 The compound (11) can be produced by reacting the compound (12) with a halogenating agent. The reaction is performed in the presence or the absence 15 of a solvent. Examples of the solvent to be used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, and 20 the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof. 25 Examples of the halogenating agent to be used in the .146 reaction include thionyl chloride, thionyl bromide, phosphorus oxychloride, phosphorus oxybromide, phosphorus pentachloride, oxalyl chloride, and phosgene. The amount of the halogenating agent to be used in the 5 reaction is usually 1 to 2 mols per 1 mol of the compound (12) and, in some cases, the halogenating agent may be used in an excess amount. The reaction temperature is usually in a range of 0*C to 150 0 C, and the reaction time is usually in a range of 0.1 to 10 24 hours. After completion of the reaction, the compound (11) can be isolated by collecting a, precipitate deposited in the reaction mixture, or concentrating the reaction mixture. The isolated compound (11) is usually used as it is in the next step 15 and, if necessary, may be further purified by recrystallization, or the like. Reference Process 8 The compound (12) can be produced by reacting a compound represented by the formula (18'): R1-a NH

(R

4 ) (18') H 20 0 wherein Ri-a, R 4 and n are as defined above (hereinafter, referred to as the compound (18')) and the compound (7).

,147 The reaction is performed in the presence or the absence of a solvent. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, tetrahydrofuran, methyl tert-butyl ether, and the like, 5 halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic polar solvents such as N,N-dimethylformamide, 10 N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and the like, and a mixture thereof. The amount of the compound (7) to be used in the reaction is usually 1 to 2 mols per 1 mol of the compound (18'). The reaction is performed in the presence of a base. 15 Examples of the base to be used include nitrogen-containing heterocyclic compounds such as pyridine, picoline, 2,6-lutidine, 1,8-diazabicyclo[5,4,0}7-undecene (DBU), 1,5-diazabicyclo[4,3,0]5-nonene (DBN), and the like, tertiary amines such as triethylamine, N,N-diisopropylethylamine, and 20 the like, inorganic bases such as potassium carbonate, sodium hydride, and the like. The amount of the base to be used is usually 1 to 2 mols per 1 mol of the compound (18'). The reaction temperature is usually in a range of 0 to 50*C, and the reaction time is usually in range of 0.1 to 24 hours. 25 After completion of the reaction, the compound (12) can ,148 be isolated by pouring the reaction mixture into water, followed by conventional extraction with an organic solvent, or collecting a deposited precipitate by filtration. The isolated compound (12) may be further purified by 5 recrystallization, chromatography, or the like. Reference Process 9 The compound (6) can be produced by reacting a compound represented by the formula (20): R' N

(R

4 )n (20) 0 10 wherein R 1 , R 4 and n are as defined above (hereinafter, referred to as the compound 20)) and the compound (10). The reaction is performed in the presence or the absence of a solvent. Examples of the solvent used in the reaction include ethers such as 1,4-dioxane, diethyl ether, 15 tetrahydrofuran, methyl tert-butyl ether, and the like, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, chlorobenzene, and the like, hydrocarbons such as toluene, benzene, xylene, and the like, nitriles such as acetonitrile, and the like, aprotic 20 polar solvents such as N,N-dimethylformamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, dimethyl sulfoxide, and the like, alcohols such as methanol, ,149 , ethanol, isopropyl alcohol, and the like, and a mixture thereof. The amount of the compound (10) to be used in the reaction is usually 1 to 2 mols per 1 mol of the compound (20). 5 The reaction temperature is usually in a range of -20 to 150 0 C, and the reaction time is usually in a range of 0.1 to 24 hours. After completion of the reaction, the compound (20) can be isolated by pouring the reaction mixture into water, and 10 extracting the mixture with an organic solvent, or collecting a deposited precipitate by filtration. The isolated Compound (20) may be further purified by recrystallization, chromatography, or the like. The compounds (3), (4) and (13) are known compounds, or 15 can be produced from known compounds according to known processes (e.g. see Organic Functional Group Preparations, 2nd edition, Vol.1, chapter 12, p.359-37 6 (Stanley R. Sandler, Wolf Karo.) or Organic Functional Group Preparations, 2nd edition, Vol.1, chapter 14, p.

434

-

465 (Stanley R. Sandler, Wolf Karo.)) 20 As an aspect of the compound (2), the following compound is mentioned: A hydrazide compound of the formula (II): '150 R 14ay R14az Xa R Ra R R8 R4b N 14 X I RRc R4C d -NR 2

-'-NH

2 0 wherein

R

1 ~ represents a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, 5 ,R2-1 represents a hydrogen atom, or a methyl group, R4a represents a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom,

R

4 b, R 4 c and R 4 d independently represent a hydrogen atom, a halogen atom, a cyano group, or a Cl-C6 alkyl group optionally 10 substituted with at least one halogen atom, or R 4 b and R 4 c are bound 'to each other at their terminal ends to form a group T: -CR 41

=CR

4 2

-CR

43 =CR44 (wherein R 41 , R 42 , R 43 and R 4 4 independently represent a hydrogen atom, a halogen atom, a cyano group, or a C1-C6 alkyl group 15 optionally substituted with at least one halogen atom), Xa represents a nitrogen atom or CR1 4 ax (wherein R 14 ax represents a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 alkoxy group optionally substituted with 151 at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally 5 substituted with at least one halogen atom), R 4 ay and R'az independently represent a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a C1-C6 10 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, 15 X1 8 represents a nitrogen atom or CRi"* (wherein R 18e represents a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom), Risa represents a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, and 20 Rlb , R 1C and R1Bd independently represent a hydrogen atom, a halogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom. The compound (10) can be produced, for example, according to the following scheme (1). 25 Scheme (1) 152 - H-N-N-QG' L -Q'(3) 1 1 R2 H--N-H A C=N-R (4) H-N-N-C-NHRl (13) cyanate or thiocyanate

H---N-C-NH

2 42 43 34, In Scheme (I), A34, L1, Q', R2, R 3 and RBa are as defined above. Among the compound (10), a compound represented by the formula (10-1): H-N-N-C-OR (10-i) 5 2 wherein R 2 , R 3 and R 6 are as defined above, can be produced, for example, according to the following scheme (2). Scheme (2) Cl-C-OR H-N--N-H H-N-N-C-ORO 2 43 or RO-C-OR 2 R b (13) 0(1_,) 10 In Scheme (2), R 2 , R 3 and R 6 are as defined above. The compound (17) can be produced, for example, according to the following Scheme (3). Scheme (3) -153 1) chloral hydrate H NH 2 OH-HC _, (R4' (R%) O 2) H2SO4

H

2 0 2 aq NH2 NaOH aq

'R

4 )H H (17) o In Scheme (3), R 4 and n are as defined above. The compounds (16), (18') and (20) can be produced, for example, according to the following Scheme (4). 5 Scheme (4) triphosgene H (HO etc 0 ) IH (R)n1 o 0 (17) (16) R 1-8-L0 R1-a -L 4 R1-aOS(0) 2 0R1-a base etc R1-a R1-a I I R4)-- base O o 0 (18') (20) In Scheme (4), R-, R 4 and n are as defined above, and L 4 represents a leaving group (e.g. a halogen atom, a methanesulfonyloxy group, a p-toluenesulfonyloxy group etc.).

154 Among the compounds (17) and (18), a compound represented by the formula (17-1): R' 3 1I 2 NH (R 4)r. (17-i) R4C.x 5N I O RX 6 5 wherein R 1 and R 4 are as defined above, R 4 cx represents a halogen atom or a cyano group, and n-i represents an integer of 0 to 3, can be produced, for example, according to the following Scheme (5). Scheme (5) R1 R' 3 3 N 4 2 NH Halogenation R 4 / 2 (R4),.1 1 (In-1 H

H

5 \ 1 H halo 6 R1 3 I (halo=the case of iodine atom) 2 NH CuCN (R.1 I OH N 6 10 0 In Scheme (5), R1, R 4 and n-i are as defined above, and halo represents a halogen atom. Among the compounds (17) and (18), a compound represented by the formula (17-11): 155

R

4 a-x R' NH 4 2 (R4)n-2 (17-) 6 0 wherein R 1 and R 4 are as defined above, R 4 a-x represents a halogen atom, R 4 c represents the same meaning as that of R 4 , and n-2 5 represents an integer of 0 to 2, can be produced, for example, according to the following Scheme (6). Scheme (6) H RH R- R 2 NH 2 NH 4 Halogenation 4 1_ 2

(R

4 ) 2 (Rt)n H R 5 H 66 R O 66 0 0 (17--) In Scheme (6), R 1 , R 4 , R 4 a-x, R 4 c and n-2 are as defined above. 10 The compound (8) can be produced, for example, according to the process shown in the following Scheme (7). Scheme (7) 156

R

7 0-C-J Hydrolysis HO--C-J (8) g I0 1) Base (LDA, n-BuLi etc ) H-J 2)

CO

2 1) Metal-halogen exchange Br-J (t-BuL i etc) (8) 2) CO 2 CHa-J Oxidation (KMnO4 etc) Oxidation H-C-J (KMnO4, Cr(VI) etc ) 0 Oxidation (KMnO4 etc) S(8) In Scheme (7), J is as defined above, R 17 represents a methyl group or an ethyl group, LDA represents lithium diisopropylamide, n-BuLi represents normal butyl lithium, and 5 t-BuLi represents tertiary butyl lithium. Among the compound (8) , a compound represented by the formula (8-1) (R 10)p HO- (8-i) 13a wherein R13a 14a, Xa, ya, Za and p are as defined above, can be 10 produced, for example, according to the process shown in the following Scheme (8). Scheme (8) ,157 R14a~p( 148) R13a-L5 base if necessary e g CuO 8 or I^ R13a-B(OH)2. Cu(II), base H R 1) Base (LDA n-BuLi etc )Y 10 HO--C 2) C0 | R In Scheme (8), R 13 a, Ri 4 a, Xa, ya, Za, p, LDA and n-BuLi are as defined above, and L 5 represents a leaving group (e.g. a halogen atom, a methanesulfonyloxy group, a p-toluenesulfonyloxy group, 5 a methylsulfonyl group etc.). Among the compound (8), a compound represented by the formula (8-11): (R 148)p HO--CKQ 0 N- (8-n) Ri9R 4da i I b 18C d 10 wherein Ri and p are as defined above, Ria, R', RiSC and R, each, independently, represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 ,158 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one 5 halogen atom, can be produced, for example, according to the process shown in the following Scheme (9). Scheme (9) Lo N- R 1 ea (R )p (R1 4 a) Rild H N Base ,N- a I18 \ /I H Rle lob HO-C 1) Base (LDA etc )I 2) CO 2 N- Rla Rlnd l0b R1 (8-n) In Scheme (9), R 1a, ia R , R ", R '8, LDA and p are as defined 10 above, and L 6 represents a leaving group (e.g. a halogen atom, a methylsulfonyl group etc.). Among the compound (8), a compound represented by the formula (8-iii): 159

CF

3 HO--C --- e 188 (8-mt) R'B 18b wherein Ris, Rl"b, RlBC, Rl'd and R le independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, a Cl-C6 alkyl group optionally substituted with at least one 5 halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a C1-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally 10 substituted with at least one halogen atom, can be produced, for example, according to the process shown in the following Scheme (10). Scheme (10) '160

R

188 HN..NHz -l18a F3 Rl 0 0

R

1 s 15b R"*

F

3 HO-C Oxidation (KMnO4 etc R RRea Rled R"Rb (8-mU) I In Scheme (10), Risa, Ri b, RiOC, R Bd and R3-" are as defined above. Among the compound (8), a compound represented by the formula (8-iv): HOR-CI 0 X18- R18a (8-iv) Ried \/ 18b 5 R wherein X represents -N=, or -CR 8e=; Risa, Ri , R18', R le and Rl18 are as defined above, and Ra-1 represents a Cl-C6 alkyl group optionally substituted with at least one halogen atom, can be produced, for example, according to the process shown 10 in the following Scheme (11).

161 Scheme (11)

R

1 7 O-C--C-CH2

-C--R

14 1 R2ONH 2 R'O--C-C-CH2-C--Rl1-1 R2O HN-,NH2 X e- 1ea

R

1 8d R14- 1 1ab

R

7 0-C X e- R lea Ried \ RI~d \ / 18b RISC R14a-1 HO-C Hydrolysis I IN X18- RWa Riad \/ 16b RIe* (8-iv) In Scheme (11), Rica-l, R , Risa, Rlab, R 1 8 ', Riad and X 18 are as defined above, and R 20 represents a methyl group or an ethyl 5 group. Among the compound (8), a compound represented by the formula (8-vii): (14b (R lb)q HO-C | (8-vi) Zb - - -- N R, i i R , b, n an1 3 b wherein R 1 3 b , R 14b Xb, yb, Zb and q are as defined above, can be -162 produced, for example, according to the process shown in the following Scheme (14). Scheme (14) (R 14) (R'*) R13b-L5' base b

R

1 7 X if necessary e g CuO R 1 7 O Z N H Rl3b-B(OH)2, Cu(II) base R1 3 b R14bq Hydrolysis tX(b - HO--C R1ab (8-vii) 5 In Scheme (14) , R1 3 b, R1 4 b, R 17 , Xb, yb, Zb, L 5 and q are as defined above. Among the compound (8), a compound represented by the formula (8-viii) and the formula (8-ix): N R 1 9 Rl1b HO-C I 11NN R13b R1' 19a X \---N X R 01 R198 R JNN 19b HO--C Ri* N%R13b 10 ( 8-vii) (8-ix) (wherein Riab is as defined above, X19 represents -N=, or -CR1 9=, Ria I R , R 1 9 C, R1 9 d and R19e, each, independently, represent .163 a hydrogen atom, a halogen atom, a cyano group, a nitro group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a C1-C6 alkoxy group optionally substituted with at least one halogen atom, a C1-C6 alkylthio group optionally 5 substituted with at 'least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom] can be produced, for example, according to the process shown 10 in the following Scheme (15). Scheme (15) 164

CHN(CH

3

)

2

R

7 0-C -7._ N NHRH Ia NHbNHNH

R

1 0- NHNH X19 + R~eR /100 R II 0 1 Ria 1 7 Rlw~ s Rs (S-viii) (8-ix) Hydrolysis Hydrolysis HO--C IlOd IN -% 3 Rld 0 R' X19- lea RlOd 0 19bHO CI (8-vii) (-ix) In Scheme (15) , R13b, R 17

R

1 9 a, R 9b, R 1 9 c, R1 9 d, L 5 and X1 are as defined above. Among the compound (7), a compound represented by the .165 formula (7-1)

L

2 -C-J 1(7-i) 0 wherein L 2 and J are as defined above, can be produced, for' example, according to the process shown in the following Scheme 5 (16). Scheme (16) HO-C-J Halogenating agent L2 _ (8) (7-i) In Scpeme (16), L 2 and J are as defined above. Among the compound (7), a compound represented by the 10 formula (7-11): L2-C-J || ( 7-it) S wherein L 2 and J are as defined above, can be produced, for example, according to the process shown in the following scheme (17). 15 Scheme (17) 1) Base H--J (LDA n-BuLi etc) 2) CS2 HS-C-J Halogenating agent L 2 --C-J 11 1) Metal-halogen exchange S Br- J (t-BuLi etc ) ( 7-. ) 2) CS 2 In Scheme (17), L 2 and J are as defined above, LDA represents lithium dilsopropylamide, n-BuLi represents normal butyl .166 lithium, and t-BuLi represents tertiary butyl lithium. Among the compound (8), a compound represented by the formula (8-v):

RI

4 ' R 14 HO-C 0R X1-- R n, (8-v) Rl'd \/ 18b R'f" 5 wherein Ri a, R 18, R 8c, R'd and X 18 are as defined above, and Ri 4 axR 14 a y and Xi 4 az independently represent a hydrogen atom, a halogen atom, a cyano group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 10 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, can be produced, for example, according to the 15 process shown in the following Scheme (18). Scheme (18) ,167 R 14a R14az R14ay R1R4ay H-C HO-C I IR4ax Oxidation 04aX 0 R (KMnO4 etc ) X 8 8a Xle- Rlea Riad \ R 1 \ AX-/ 18b 18b Rlc R (21) ( 8-v) In Scheme (18), Risa, Rl 8 b, R 18 c, RlBd, X18, R 4 ax, Ri 4 ay and X 14 a3 are as defined above. 5 The compounds (21) in scheme (18) can be produced, for example, according to the process shown in the following Scheme (19). Scheme (19) -168 R14aX R 14" R14y H R14ay H Rl 4 ax 0 H R14ax or or L0 1se B(OH) 2 Le R 18 e B(OH) 2 R Nd R R8 RlReid N- eia N-N~18 R R8d a R1 \ ~R R cR~ Base Cu(OAc) 2 Base Cu(OAc) 2 Rl4a" R14a R1 4 ay H R1 4 ay R14ax POC 3 R14ax isa DMF 1 X1-- 1ea DM X18- Rl 8a R led Rlad 18b sbC R1ac R " (21)

NH

2 (in case X 18 - R 1 R 14ax = R14Ry = R\4" R/ R\ =H) lb Rl'

H

3 CO - > CH 3 In Scheme (19) , Risa, R b , RiSc, R1 a, Rlo", X e, R 14 ax, R1 4 ay, X1435 and L 6 are as defined above. 5 Among the compounds (21) in scheme (18) , a compound represented by the formula (21-1), the formula (21-11), and the formula (21-111): -169 ... 4 ha lo (y) h a lo (y) H halo(x) 0 halo(x) X18- a X1- Rea X -- Riea

R

1 dX R8d R I Xd RiSc Rieb Rue R Ric RS ( 21-1) ( 21-11) ( 21 -in) wherein Risa, R 1b, Ric, R 1d and X 1 are as defined above, and halo(x) and halo (y) independently represent a halogen atom, can be produced, for example, according to the process shown in the 5 following Scheme (20). Scheme (20) halo(y) H H-C 0 halo(x) XR RIa and / or X' a Rea 18b 18b Halogenating R "" R agent (1 eq) (21-1) 21-1) H-1C 0 N Halogenating alogenating agent agent R ~ la(Ieq) 0 eq) RX )R b Halogenating R 18 R agent halo(y) C~~eq) H-C-'I (1 9 H 'N"%halo(x) (R R = R4a"= H) X -Rua RiS Rlec Rl ( 21-ni) In Scheme (20), Risa, Rb, Riac Rls, X1l, halo (x) and halo(y) are as defined above.

.170 Among the compound (8), a compound represented by the formula (8-vi): R14ay-1 HO-C sIoI -30 X18-8 XRs' R188 (8-vi) RR 16Sb 180 R18C 5 wherein Risa R15, Risc, Rled and X 18 are as defined above, R1 4 ay represents a hydrogen atom or a halogen atom, R 30 represents a Cl-C6 alkyl group optionally substituted with at least one halogen atom, and r represents an integer of 0 to 2, can be produced, for example, according to the process shown in the 10 following Scheme (21). Scheme (21) 171 R14ay-1 R14ay-1 R14ay-1 H thiocyanate H S-CN H H X- R Br 2 le X Ra Na 2 S X18. 18a R18R R R'a \d-s Ra \8 R 18d\ R'sc Rs Ris R Rise R1s (21)

(R'

4 " = R 1 4 = H,

R

14 ,y = H or halo) R'14y- R 14ay-1 R3L4 -COxidation H-C 30 1-20-ec N S(O)__R 30 Base 0-Ro (H 2

O

2 etc)-Ro X1 18a X18 R18a Ri \d

R

1 " \I / Ri1c R b Rsc R (r=lor2) Oxidation Oxidation (KM nO4, etc) (KMnO 4 , etc) R(14ay-1 R O44C" Oxidation 3/ HO--QR3 (H-202. HO-a 0-R 3 0 KMnO 4 , etc) 0 S(O)rR Xi- R188 X a- Rie RI R1 1d / 18b s18b Ri8c R 18C R ( 8-vi) ( 8-vi) (r =0) (r=1 or2) In Scheme (21) , Risa, Rlb , Risc, Rid, X18 , R1 4 ay-1 , R 30 , r and L 4 are as defined above. 5 The specific examples of the present compound are summarized in the following tables. A compound represented by the formula (1-A): 172 R4a1 N 3 3 NH R(1-A) (Rk 2n 1;Z f"-NH-NH-C--R' 6 X31 wherein R, A31, (R), Ri 3 a-l and R14a-1 are combinations shown in Table 1 to Table 7.

173 Table 1 R 5 A 3 1 (R') R13- R 4-I H 0 3-CR 3 , 5-Cl 3-chloro-2-pyridflyl H H 0 3-Br, 5-Cl 3-chloro-2-pyridifyl H H1 0 3-Br, 5-Br 3-chloro-2-pyridifyl H H 0 3-CH 3 ,, 5-CN 3-chloro-2-pyridinyl H H 0 3-CR 3 , 5-Cl 3-chloro-2-pyrdinfyl C 1 H 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl Cl H 0 3-Br, 5-Br 3-chloro-2-pyridlflyl Cl H 0 3-CH 3 , 5-CN 3-chloro-2-pyridinfyl Cl H 0 3-CR 3 , 5-Cl 3-chloro-2-pyridlflyl Br H 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br H 0 3-Br, 5-Br 3-chloro-2-pyrdinfyl Br H 0 3-CH 3 , 5-CN 3-chloro-2-pyridiflyl Br H 0 3-CH 3 , 5-Cl 3-chloro-2-pyrid-nyl CF 3 H 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl

CF

3 H 0 3-Br, 5-Br 3-chloro-2-pyridinyl

CF

3 H 0 3-CR 3 , 5-CN 3-chloro-2-pyrid-flyl CF 3

CH

3 0 3-CR 3 , 5-Cl 3-chloro-2-pyridiflyl H

CR

3 0 13-Br, 5-Cl 3-chloro-2-pyridinyl H

CR

3 0 13-Br, 5-Br 3-chloro-2-pyrdinfyl H

CR

3 0 13-CR 3 , 5-CN 3-chloro-2-pyrid~iny1 H

CR

3 0 13-CH 3 , 5-Cl 3-chloro-2-pyridiflyl Cl

CR

3 0 13-Br, 5-Cl 3-chloro-2-pyridinyl Cl

CR

3 0 13-Br, 5-Br 3-chloro-2-pyridinfyl Cl

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridiflyl Cl

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br

CR

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridiflyl Br

CR

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridiflyl Br

CH

3 0 3-CR 3 , 5-Cl 3-chloro-2-pyridinyl

CF

3

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl

CF

3

CR

3 0 3-Br, 5-Br 3-chloro-2-pyridiflyl

CF

3

CR

3 .0 3-CR 3 , 5-CN 3-chloro-2-pyridinyl

CF

3 174 Table 2

A

31

(R

4 )n ______ R _ _

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridiflyl H

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyrdinyl H

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridiyl H

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl Cl

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridiCyl Cl

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl Cl

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl

CH

2

CH

3 0 3-Cl 3 , 5-Cl 3-chloro-2-pyridinyl Br

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridiiyl CF 3 CH (CH 3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyriclifyl H CH (CH 3 ) 2 0 3-Br, 5-C 3-chloro-2-pyridiyl H CH (CH 3 ) 2 0 3-Br, 5-Br 3-chloro-2-pyridinyl H CH (CH 3 ) 2 0 3-C 3 , 5-CN 3-chloro-2-pyridinyl H CH (CH 3 ) 2 0 3-CC 3 , 5-Cl 3-chloro-2-pyr1dnyl Cl CH (CH 3 ) 2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl CH (CH 3 ) 2 0 3-Br, 5-Br 3-chloro-2-pyridinyl Cl CO (CH 3

)

2 0 3-Cl 3 , 5-CN 3-chloro-2-pyridinyl C1 CH (CH 3 ) 2 0 3-C 3 , 5-Cl 3-chloro-2-pyridinyl Br

CHO(C

3

)

2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br CHO(C1 3

)

2 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br CH (CH 3 ) 2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br CH (CH 3 ) 2 0 3-Cl 3 , 5-Cl 3-chloro-2-pyridinyl CF 3

CH(CH

3

)

2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3

CH(CH

3

)

2 0 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3 CH (CH 3

)

2 0 3-Cl 3 , 5-CN 3-chloro-2-pyridinyl CF 3 175 Table 3

R

5

A

1

(R

4 ), R _13a-1 R ia-I C (CH 3 ) 3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

C(CH

3

)

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H C (CH 3

)

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl H

C(CH

3

)

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H C (CH 3 ) 3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl C1 C (CH 3 ) 3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl C (CH 3 ) 3 0 3-Br, 5-Br 3-chloro-2-pyridinyl Cl

C(CH

3

)

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl C (CH 3 ) 3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br C (CH 3 ) 3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br

C(CH

3

)

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br

C(CH

3 3 0 3-CH3, 5-CN 3-chloro-2-pyridinyl Br C (CH 3 ) 3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3

C(CH

3

)

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3

C(CH

3

)

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3

C(CH

3

)'

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl CF 3

CF

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridil H

CF

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H

CF

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl H

CF

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CF

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyrCd1nyl Cl

CF

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl

CF

3 0 3-Br, 5-Br 3-chCoro-2-pyrldinyl Cl

CF

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl

CF

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br

CF

3 0 3-Br, 5-Cl 3-chloro-2-pyridnyl Br

CF

3 0 3-Br, 5-Br 3-chloro-2-pyriinyl Br

CF

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br

CF

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3

CF

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3

CF

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3

CF

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl CF 3 .176 Table 4 R 5

A

3 1 (R)

R

13 R14a-1

CH

2

OCH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl H

CH

2

OCH

3 0 3-Br, 5-Cl 3-chloro-2-pyr-dilrl H

CH

2

OCH

3 0 3-Br, 5-Br 3-chloro-2-pyr2.dlfyl H

CH

2

QCH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CH

2

OCH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl C1

CH

2

OCH

3 0 3-Br, 5-Cl 3-chloro-2-pyr3-dinyl Cl

CH

2

OCH

3 0 3-Br, 5-Br 3-chloro-2-pyrCldnyl Cl

CH

2

OCH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl C11 2 0CH 3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl Br

CH

2 0CH 3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl Br

CH

2 00H 3 0 3-Br, 5-Br 3-chloro-2-pyrCdlnyl Br

CH

2

OCH

3 0 3-CH 3 i 5-CN~ 3-chloro-2-pyridiflyl Br

CH

2 0CH 3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridaflyl

CF

3

CH

2 0CH 3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl

CF

3

CH

2 0CH 3 0 3-Br, 5-Br 3-chloro-2-pyridiyl

CF

3

CH

2 0CH 3 0 3-CH 3 , 5-CN 3-chloro-2-pyridifyl

CF

3

CH

2

SCH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

CH

2

SCH

3 0 3-Br, 5-Cl 3-chloro-2-pyrdinfl H

CH

2

SCH

3 0 3-Br, 5-Br 3-chloro-2-pyridlflyl H

CH

2

SCH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridlflyl H

CH

2

SCH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl Cl

CH

2

SCH

3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl Cl

CH

2

SCH

3 0 3-Br, 5-Br 3-chloro-2-pyridiflyl Cl

CH

2

SCH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyr2.diflyl Cl

CH

2 sCH 3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinfyl Br

CH

2

SCH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinfyl Br

CH

2

SCH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br

CH

2

SCH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridlflyl Br

CH

2

SCH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl

CF

3

CI-

2

SCH

3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl

CF

3

CH

2

SCH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl

CF

3

CH

2

SCH

3 10 3-CH 3 , 5-CN 3-chloro-2-pyridinfyl

CF

3 ,177 Table 5 R5A 31 (R') ~ R 13 a- 1 4

CH

2 N (CHO 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

CH

2 N (CHO 2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H

CH

2

N(CH

3

)

2 0 3-Br, 5-Br 3-chloro-2-pyridinyl H

CH

2

N(CH

3

)

2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CH

2 N (CH 3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl C1

CH

2

N(CHO)

2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl

CH

2

N(CH

3

)

2 0 3-Br, 5-Br 3-chloro-2-pyridinyl Cl

CH

2

N(CH

3

)

2 0 3-CH 3 5-CN 3-chloro-2-pyr-d-nyl Cl

CH

2

N(CH

3

)

2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridnyl Br

CH

2

NO(CHO

2 0 3-Br, 5-Cl 3-chloro-2-pyridifyl Br

CH

2

N(CHO

2 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br

CH

2

N(CH

3

)

2 0 3-CH 3 , 5-C 3-chloro-2-pyridifyl Br

CH

2

I'(CHO)

2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3

CH

2

N(CHO)

2 0 3-Br, 5-Cl 3-chloro-2-pyridifyl CF 3

CH

2 N (CHO 2 0 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3

CH

2 N (CHO 2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl CF 3 cyclopropyl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridil H cyclopropyl 0 3-Br, 5-Cl 3-chloro-2-pyridiyl H cyclopropyl 0 3-Br, 5-Br 3-chloro-2-pyrdifyl H cyclopropyl 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H cyclopropyl 0 3-CH 3 C 5-Cl 3-chloro-2-pyridilyl Cl cyclopropyl 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl cycloropyl 0 3-Br, 5-Br 3-chloro-2-pyridinyl Cl cyclopropyl 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl cyclopropyl 0 3-CH 3 5-Cl 3-chloro-2-pyridinyl Br cyclopropyl 0 3-Br, 5-Cl 3-chloro-2-pyridiyl Br cyclopropyl 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br cyclopropyl 0 3-CH 3 , 5-CS 3-chloro-2-pyridinyl Br cyclopropyl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3 cyclopropyl 0 3-Br, 5-Cl 3-chloro-2-pyridiyl CF 3 cyclopropyl 0 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3 cyclopropyl 0 3-CH 3 , 5-CC 3-chloro-2-pyridiryl CF 3 178 Table 6

R

5

A

3 1 (RR) R 13 a 1 Ru_a-I cyclobutyl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H cyclobutyl 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl H cyclobutyl 0 3-Br, 5-Br 3-chloro-2-pyrid-nyl H cyclobutyl 0 3-CH 3 , 5-CN 3-chloro-2-pyridflyl H cyclobutyl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Cl cyclobutyl 0 3-Br, 5-Cl 3-chloro-2-pyridilyl Cl cyclobutyl 0 3-Br, 5-Br 3-chloro-2-pyridflYl Cl cyclobutyl 0 3-CH 3 , 5-CN 3-chloro-2-pyriinyl Cl cyclobutyl 0 3-CH- 3 , 5-Cl 3-chloro-2-pyridflYl Br cyclobutyl 0 3-Br, 5-Cl 3-chloro-2-pyridflYl Br cyclobutyl 0 3-Br, 5-Br 3-chloro-2-pyridflYl Br cyclobutyl 0 3-CH 3 , 5-CN 3-chloro-2-pyridflyl Br cyclobutyl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridflYl

CF

3 cyclobutyl 0 3-Br, 5-Cl 3-chloro-2-pyrdinfyl

CF

3 cyclobutyl 0 3-Br, 5-Br 3-chloro-2-pyrdifyl

CF

3 cyclobutyl 0 3-CH 3 , 5-CN 3-chloro-2-pyrdinfyl

CF

3 cyclopentyl 0 3-CH 3 , 5-Cl, 3-chloro-2-pyridinfyl H cyclopentyl 0 3-Br, 5-Cl 3-chloro-2-pyr.dlYl H cyclopentyl 0 3-Br, 5-Br 3-chloro-2-pyrldflYl H cyclopentyl 0 3-CM 3 , 5-CN 3-chloro-2-pyrldflyl H cyclopentyl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridflyl Cl cyclopentyl 0 13-Br, 5-Cl 3-chloro-2-pyridflyl Cl cyclopentyl 0 3-Br, 5-Br 3-chloro-2-pyrdinfYl Cl cyclopentyl 0 3-CH 3 , 5-CN 3-chloro-2-pyridflYl Cl cyclopentyl 0 3-CH 3 , 5-Cl 3-chloro-2-pyr.dllyl Br cyclopentyl 0 3-Br, 5-Cl 3-chloro-2-pyr.dfyl Br cyclopentyl 0 3-Br, 5-Br 3-chloro-2-pyr-dinyl Br cyclopentyl 0 3-CM 3 , 5-CN 3-chloro-2-pyr-dllYl Br cyclopentyl 0 3-CH 3 , 5-Cl 3-chloro-2-pyr.dinfyl

CF

3 cyclopentyl 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl

CF

3 cyclopentyl 0 3-Br, 5-Br 3-chloro-2-pyri.dinyl

CF

3 cyclopny 0 3-CM 3 , 5-CN I3-chloro-2-pyridflYl

CF

3 179 Table 7

R

5

A

3 1 (RR) iR 13a-1_R14a-1 cyclohexyl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl H cyclohexyl 0 3-Br, 5-Cl 3-chloro-2-pyridflyl H cyclohexyl 0 3-Br, 5-Br 3-chloro-2-pyridflyl H cyclohexyl 0 3-CH 3 , 5-CN 3-chloro-2-pyrldflyl H cyclohexyl 0 3-CM 3 , 5-Cl 3-chloro-2-pyridflyl Cl cyclohexyl 0 3-Br, 5-Cl 3-chloro-2-pyridflYl Cl cyclohexyl 0 3-Br, 5-Br 3-chloro-2-pyridinyl C1 cyclohexyl 0 3-CM 3 , 5-CN 3-chloro-2-pyridinyl C1 cyclohexyl 0 3-CM 3 , 5-Cl 3-chloro-2-pyrdinflY Br cyclohexyl 0 3-Br, 5-Cl 3-chloro-2-pyridflyl Br cyclohexyl 0 3-Br, 5-Br 3-chloro-2-pyridinfyl Br cyclohexyl 0 13-CH,, 5-CN 3-chloro-2-pyridflyl Br cyclohexyl 0 13-CM 3 , 5-Cl 3-chloro-2-pyridlflyl

CF

3 cyclohexyl 0 13-Br, 5-Cl 3-chloro-2-pyridflyl

CF

3 cyclohexyl 0 3-Br, 5-Br 3-chloro-2-pyridlflyl

CF

3 cyclotiexyl 0 3-CM 3 , 5-CN 3-chloro-2-pyridilyl

CF

3 phenyl 0 3-CM 3 , 5-Cl 3-chloro-2-pyridflyl H phenyl 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H phenyl 0 3-Br, 5-Br 3-chloro-2-pyridinYl H phenyl 10 3-CM 3 , 5-CN 3-chloro-2-pyridflyl H phenyl 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdinfyl_ Cl phenyl 0 3-Br, 5-Cl1 3-chloro-2-pyridlflyl C1 phenyl 0 3-Br, 5-Br 3-chloro-2-pyrd-fyl Cl phenyl 0 3-CH 3 , 5-CN 3-chloro-2-pyr-dinyl Cl pheny1 0 3-CM 3 , 5-Cl 3-chloro-2-pyridiflyl Br phenyl 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl Br phenyl 0 3-Br, 5-Br 3-chloro-2-pyridinfyl Br phenyl 0 3-CM 3 , 5-CN 3-chloro-2-pyridinyl Br phenyl 0 3-CM 3 , 5-Cl 3-chloro-2-pyridilyl

CF

3 phenyl 0 3-Br, 5-Cl 3-chloro-2-pyridilyl

CF

3 phenyl 0 3-Br, 5-Br 3-chloro-2-pyridilyl

CF

3 phenyl 10 3-CM 3 , 5-CN 13-chloro-2-pyridinfyl

CF

3 -180 A compound represented by the formula (1-B): R1 4 a-1 N 31 3R 3 a-1 (1-B)

(R

4 )n [ !:: -NH-NH-C--OR 6 6 132 6 32 Aa wherein R , A , (R 4 )n, R ia-i and Ria-i represent combinations shown in Table 8 to Table 31. 5 Table 8

R

6

A

32 (R')n R

_

13a-1 Ri14a-1

CH

3 0 3-CH 3 3-chloro-2-pyridinyl H

CH

3 , 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

CH

3 0 3-CH 3 , 5-Br 3-chloro-2-pyridinYl H

CH

3 0 3-CH 3 , 5-I 3-chloro-2-pyridinyl H

CH

3 0 3-CH 3 , 5-CH 3 3-chloro-2-pyridfyl H

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CH

3 0 3-Cl 3-chloro-2-pyridinyl H

CH

3 0 3-C1, 5-Cl 3-chloro-2-pyridinyl H

CH

3 0 3-Cl, 5-Br 3-chloro-2-pyridinyl H

CH

3 0 3-C1, 5-I 3-chloro-2-pyridinyl H

CH

3 0 3-C1, 5-CH 3 3-chloro-2-pyridinyl H

CH

3 0 3-Cl, 5-CN 3-chloro-2-pyridinyl H

CH

3 0 3-Br 3-chloro-2-pyridinyl H

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl H

CH

3 0 3-Br, 5-I 3-chloro-2-pyridinyl H

CH

3 0 3-Br, 5-CH 3 3-chloro-2-pyridinyl H

CH

3 0 3-Br, 5-CN 3-chloro-2-pyridinyl H

CH

3 0 3-I 3-chloro-2-pyridinyl H

CH

3 0 3-I, 5-Cl 3-chloro-2-pyridinyl H

CH

3 0 3-I, 5-Br 3-chloro-2-pyridinyl H

CH

3 0 3-I, 5-I 3-chloro-2-pyridinyl H

CH

3 0 3-I, 5-CH 3 3-chloro-2-pyridinyl H

CH

3 ,0 3-I, 5-CN 3-chloro-2-pyridinyl

H

.181 Table 9 R 6 (R2 1a-)R14

CH

3 0 3-CH3 3-chloro-2-pyridifyl F

CH

3 0 3-CH 3 , 5-Br 3-chloro-2-pyridinyl F

CH

3 0 3-CH 3 , 5-I 3-chloro-2-pyridinyl F

CH

3 0 3-FH 3 , 5-i 3-chloro-2-pyridlfyl F

CH

3 0 3-CH 3 5-CN 3-chloro-2-pyridifyl F

CH

3 0 3-C1, 3-chloro-2-pyr5-dCyl F

CH

3 0 3-Cl,5C 3-chloro-2-pyridlflyl F Gil 3 0 3-Cl, 5 -BrC 3-chloro-2-pyridinfyl F Gil 3 0 3-Cl, 5-Ir 3-chloro-2-pyr-d3nyl F

CH

3 0 3-Cl, 5-G1 3:chloro-2-pyridlyl F

GH

3 0 3-C1, 5-GN3 3-chloro-2-pyridflyl F Gil 3 0 3-Br 5C 3-chloro-2-pyridinyl F

GH

3 0 3-Br,5C 3-chloro-2-pyr-dllyl F Gil 3 0 3-Br, 5-Br 3-chloro-2-pyridiflyl F Gil 3 0 3-Br, 5-Ir 3-chloro-2-pyr3.dlfyl F Gil 3 0 3-Br, 5-Gil 3-chloro-2-pyridinyl F

CH

3 0 3-Br, 5-CH3 3-chloro-2-pyridinly F Gil 3 0 3-Ir 5C 3-chloro-2-pyridflyl F Gil 3 0 3-I, 5-Cl 3-chloro-2-pyridiflyl F Gil 3 0 3-I, 5-Br 3-chloro-2-pyridflyl F Gil 3 '0 3-I, 5-I 3-chloro-2-pyr3.dinyl F Gil 3 10 3-I, 5-GH 3 3-chloro-2-pyridiflyl F

CH

3 10 3-I, 5-GN 3-chloro-2-pyridiflylF 182 Table 10

R

6 A 3 2 R__ _ __ _ _ 13a-1 __ __ _ __ R 14-1 CH3 0 3-CH 3 3-Chloro-2-pyrldlnyl Cl

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Cl

CH

3 0 3-CH 3 , 5-Br 3-chloro-2-pyridinfyl Cl

CH

3 0 3-CH 3 r 5-1 3-chloro-2-pyridlnyl Cl

CH

3 0 3-CH 3 , 5-CH- 3 3-chloro-2-pyr-dinfyl Cl

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridnyl C1

CH

3 0 3-Cl 3-chloro-2-pyridinyl Cl

CH

3 0 3-Cl, 5-Cl 3-chloro-2-pyridnyl Cl

CH

3 0 3-Cl, 5-Br 3-chloro-2-pyridinyl Cl

CH

3 0 3-Cl, 5-I 3-chloro-2-pyridifyl Cl

CH

3 0 3-Cl, 5-CH 3 3-chloro-2-pyridifyl Cl

CH

3 0 3-Cl, 5-CN 3-chloro-2-pyridinyl C1

CH

3 0 3-Br 3-chloro-2-pyridinyl Cl

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyr3.dlfyl Cl

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridilyl Cl

CH

3 0 3-Br, 5-I 3-chloro-2-pyridinyl Cl

CH

3 0 3-Br, 5-CH- 3 3-chloro-2-pyri~difyl C1

CH

3 0 3-Br, 5-CN 3-chloro-2-pyridiflyl C1 Cl- 3 0 3-1 3-chloro-2-pyridiflyl Cl

CH

3 0 3-I, 5-Cl 3-chloro-2-pyr3-dlfyl C1

CH

3 0 3-I, 5-Br 3-chloro-2-pyridifyl C1

CH

3 0 3-I, 5-I 3-chloro-2-pyridifyl Cl

CH

3 0 3-I, 5-CH 3 3-chloro-2-pyr3-dilyl ICl

CH

3 0 3-I, 5-CN 3-chloro-2-pyridflyl, ICl 183 Table 11 R6 A32 (R 4 ) R 3 a R

CH

3 0 3-CH 2

CH

3 3-chloro-2-pyridinyl Cl

CH

3 0 3-CH (CH 3 ) 2 3-chloro-2-pyridinyl Cl

CH

3 0 3-C(CH 3

)

3 3-chloro-2-pyridinyl Cl

CH

3 0 3-CF 3 3-chloro-2-pyridiyl Cl

CH

3 0 3-OCHC 3-chloro-2-pyrldnyl Cl

CH

3 0 3-phenyl 3-chloro-2-pyridinyl Cl

CH

3 0 3-CH 2

CH

3 , 5-Cl 3-chloro-2-pyridinyl C1

CH

3 0 3-CH(CH 3 )C 2 5-Cl 3-chloro-2-pyridinyl 01

OH

3 0 3-(CH 3

)

3 , 5-Cl 3-chloro-2-pyridinyl Cl

CH

3 0 3-OF 3 , 5-0l 3-chloro-2-pyridinyl 01

CH

3 0 3-CCH 3 , 5-Cl 3-chloro-2-pyriinyl cl

CH

3 0 3-phenyl, 5-Cl 3-chloro-2-pyridinyl Cl

CH

3 0 3-OH 3 , 4-01 3-chloro-2-pyridinyl Cl

CH

3 0 3-01, 4-01 3-chloro-2-pyridinyl Cl

CH

3 0 3-OH 3 , 6-Cl 3-chCoro-2-pyrldinyl Cl

CH

3 0 3-C1, 6-01 3-chloro-2-pyridinyl Cl

CH

3 0 3-OH 3 , 4-C1, 5-01 3-chloro-2-pyridinyl 01

CH

3 0 3-Cl, 4-Cl, 5-Cl 3-chloro-2-pyridinyl Cl

OH

3 0 3-OH 3 , 5-01, 6-Cl 3-chloro-2-pyridifl Cl

CH

3 0 3-Cl, 5-Cl, 6-Cl 3-chloro-2-pyridinyl Cl

OH

3 0 3-OH 3 , 5-F 3-chloro-2-pyrCdlyl 01

CH

3 0 3-01, 5-F 3-chloro-2-pyridinyl Cl

OH

3 0 3-Br, 5-F 3-chloro-2-pyridinyl C1

OH

3 0 3-C, 5-F 3-chloro-2-pyridinyl Cl

OH

3 0 3-Me,4,5-CHH-CH=CH- 3-chloro-2-pyridinyl Cl

OH

3 10 3-Ol,4,5-OHOCH-OH=CH- 3-chloro-2-pyridinyl Cl

OH

3 10 3-Br,4,5-CHCH-OHCH- 3-chloro-2-pyriciinyl Cl

OH

3 10 3-I,4,5-CHOCH-CH=CH- 3-chloro-2-pyrid-nyl

C

,184 Table 12

R

6

A

3 2 (R_)________R Rla-I

CH

3 0 3-CH 3 3-chloro-2-pyrdinyl Br

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br

CH

3 0 3-CH 3 , 5-Br 3-chloro-2-pyridinyl Br

CH

3 0 3-CH 3 , 5-I 3-chl oro-2-pyr1dinyl Br

CH

3 0 3-CH 3 , 5-CH 3 3-chloro-2-pyridinyl Br

CH

3 0 3-C 3 , 5-CN 3-chloro-2-pyridinyl Br

CH

3 0 3-Cl 3-chloro-2-pyridinyl Br

CH

3 0 3-Cl, 5-Cl 3-chloro-2-pyrdinyl Br

CH

3 0 3-Cl, 5-Br 3-chloro-2-pyridinyl Br

CH

3 0 3-Cl, 5-I 3-chloro-2-pyridinyl Br Cl 3 0 3-C1, 5-CH 3 3-chloro-2-pyridinyl Br

CH

3 0 3-C1, 5-CN 3-chloro-2-pyridinyl Br

CH

3 0 3-Br 3-chloro-2-pyridinyl Br

CO

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br

CO

3 0 3-Br, 5-Br 3-chloro-2-pyricinyl Br

CH

3 0 3-Br, 5-I 3-chloro-2-pyridinyl Br

CH

3 0 3-Br, 5-CH 3 3-chloro-2-pyridinyl Br

CH

3 0 3-Br, 5-CN 3-chloro-2-pyridinyl Br

CH

3 0 3-I 3-chloro-2-pyridinyl Br

CH

3 0 3-1, 5-Cl 3-chloro-2-pyridinyl Br

CH

3 0 3-I, 5-Br 3-chloro-2-pyridnyl Br

CH

3 0 3-1, 5-I 3-chloro-2-pyridinyl Br

CH

3 0 3-1, 5-Cl 3 3-chloro-2-pyrdinyl Br

CH

3 0 3-, 5-CM 3-chloro-2-pyridinyl Br ,185 Table 13

R

6

A

3 2 (R)Ra

CH

3 0 3-CHOH, 3-chloro-2-pyridlfyl Br

CH

3 0 3-CH (H 3

)

2 3-chloro-2-pyridinyl Br

CH

3 0 3-C(CH 3 3 3-chloro-2-pyrdifyl -Br

CH

3 0 3-CF 3 3-chloro-2-pyridifyl Br

CH

3 0 3-OCH 3 3-chloro-2-pyrdifyl Br

CH

3 0 3-phenyl 3-chloro-2-pyridifyl Br

CH

3 0 3-CH 2

CH

3 , 5-Cl 3-chloro-2-pyridlflyl Br

OH

3 10 3-OH (CH 3 ) 2 , 5-Cl 3-chloro-2-pyridilyl Br

OH

3 10 3-C (CH 3 ) 3 , 5-Cl 3-chloro-2-pyridlflyl Br

OH

3 0 13-CF 3 , 5-Cl 3-chloro-2-pyrdinyl Br

CH

3 0 3-00H 3 , 5-Cl 3-chloro-2-pyrldlflyl Br

CH

3 0 3-phenyl, 5-Cl 3-chloro-2-pyridinfyl Br

OCH

3 .0 3-OH 3 , 4-Cl 3-chloro-2-pyrid3-nyl Br

OH

3 10 3-Cl, 4-Cl 3-chloro-2-pyr.d3nyl Br

OH

3 10 3-OH 3 , 6-Cl 3-chloro-2-pyridiflyl Br

OH

3 10- 3-01, 6-Cl 3-chloro-2-pyridinfyl Br

OH

3 0 3-OH 3 , 4-01, 5-01 3-chloro-2-pyridi-nyl Br

CH

3 0 3-01, 4-01, 5-Cl 3-chloro-2-pyridinyl Br

OH

3 0 3-OH 3 , 5-01, 6-01 3-chloro-2-pyrciinyl Br

OH

3 -0 3-Cl, 5-01, 6-01 3-chloro-2-pyr3.nyl Br

OH

3 10 3-CH 3 , 5-F 3-chloro-2-pyrldlflyl Br

OH

3 10 3-Cl, 5-F 3-chloro-2-pyr-dinfyl Br

OH

3 10 3-Br, 5-F 3-chloro-2-pyridinfyl Br

OH

3 10 3-1, 5-F 3-chloro-2-pyridinfyl Br

OH

3 10 [3-Me,4,5-CH=H-CH=CH- 3-chloro-2-pyr3.dlfyl Br

OH

3 0 13-Ol,4,5-H=OH-CH=CH- 3-chloro-2-pyridinyl Br

OH

3 0 13-Br,4,5-OH=CH-OHOCH- 3-chloro-2-pyridinyl Br

OH

3 0 13-I,4,5-CHCH-CH=CH- 3-chloro-2-pyridinfyl Br 186 Table 14 R 6 A 32 (WR 3 a-I R1 0-1

CH

3 0 3-CH 3 3-chloro-2-pyridinyl I

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdinyl I

CH

3 0 3-CH 3 , 5-Br 3-chloro-2-pyridinyl I

CH

3 0 3-CH 3 , 5-I 3-chloro-2-pyridifyl I

CH

3 0 3-CH 3 , 5-CH 3 3-chloro-2-pyridiyl I

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl I

CH

3 0 3-Cl 3-chloro-2-pyridinyl I

CH

3 0 3-Cl, 5-Cl 3-chloro-2-pyridlflyl I

CH

3 0 3-Cl, 5-Br 3-chloro-2-pyridiflyl I

CH

3 0 3-Cl, 5-I 3-chloro-2-pyridiflyl I

CH

3 0 3-Cl, 5-CH 3 3-chloro-2-pyridinyl. I

CH

3 0 3-Cl, 5-CN 3-chloro-2-pyridiflyl I

CH

3 0 3-Br 3-chloro-2-pyridil I

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl I

CH

3 0 3-Br, 5-Br 3-chloro-2-pyr.dil I

CH

3 0 3-Br, 5-I 3-chloro-2-pyridinfyl I

CH

3 0 3-Br, 5-CH 3 3-chloro-2-pyridiflyl I

CH

3 0 3-Br, 5-CN 3-chloro-2-pyr-dlyl I

CH

3 0 3-I 3-chloro-2-pyridlflyl I

CH

3 0 3-I, 5-Cl 3-chloro-2-pyrdinfyl I

CH

3 0 3-I, 5-Br 3-chloro-2-pyridiflyl I

CH

3 0 3-1, 5-I 3-chloro-2-pyrldflyl I

CH

3 0 3-1, 5-CH 3 3-chloro-2-pyridilyl I

CH

3 0 3-1, 5-CN~ 13-chloro-2-pyridinryl

I

.187 Table 15 R 6 A 32 R1a1R' 0-1

CH

3 0 3-CH 3 3-chloro-2-pyr3.dlfyl

CH

3

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl CH 3

CH

3 0 1 3-CH 3 , 5-Br 3-chloro-2-pyridifyl CH 3 Cl-I 3 0 3-CH 3 , 5-I 3-chloro-2-pyridifyl CH 3

CH

3 0 3-CH 3 , ,5-CH 3 3-chloro-2-pyridinyl

CH

3

CH

3 0 3 7

CH

3 , 5-CN 3-chloro-2-pyridifll

CR

3

CH

3 0 3-C1 3-chloro-2-pyridinyl CH 3

CH

3 0 3-Cl, 5-Cl 3-chloro-2-pyridlflyl CH 3

CH

3 0 3-Cl, 5-Br 3-chloro-2-pyrilnyl Cl 3

CH

3 0 3-Cl, 5-1 3-chloro-2-pyridinyl

CH

3

CR

3 0 3-Cl, 5-CR 3 3-chloro-2-pyridifyl

CH

3

CH

3 0 3-Cl, 5-CN 3-chloro-2-pyridlflyl

CR

3

CR

3 0 3-Br 3-chloro-2-pyridifyl CH 3

CR

3 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl

CH

3

CH

3 0 3-Br, 5-Br 3-chloro-2-pyr-dllyl

CR

3

CH

3 0 3-Br, 5-I 3-chloro-2-pyridiflyl

CH

3

CH

3 0 3-Br, 5-CH 3 3-chloro-2-pyrdinfyl

CR

3

CH

3 0 3-Br, 5-CN 3-chloro-2-pyridinyl

CH

3

CR

3 0 3-1 3-chloro-2-pyridinyl

CH

3

CR

3 0 3-I, 5-Cl 3-chloro-2-pyridiflyl

CH

3

CH

3 0 3-I, 5-Br 3-chloro-2-pyridiflyl

CH

3

CH

3 0 3-1, 5-I 3-chloro-2-pyridifyl

CH

3

CH

3 0 3-1, 5-CH 3 3 chloro-2-pyridifyl

CH

3

CH

3 0 3-1, 5-CN 3-chloro-2-pyridifyl

CR

3 ,188 Table 16 RA (R)n R1 3 a-1 R14a-1 CH3 0 3-CH3 3-chloro-2-pyridinyl CF 3 CH3 0. 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3

CH

3 0 3-CH 3 , 5-Br 3-chloro-2-pyridinyl CF 3

CH

3 0 3-CH 3 , 5-I 3-chloro-2-pyridinyl CF 3

CH

3 0 3-CH3, 5-CH 3 3-chloro-2-pyridinyl CF 3

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl CF 3 CH3 0 3-C1 3-chloro-2-pyridinyl CF 3

CH

3 0 3-Cl, 5-Cl 3-chloro-2-pyridinyl CF 3 CH3 0 3-C1, 5-Br 3-chloro-2-pyridinyl CF 3

CH

3 0 3-C1, 5-I 3-chloro-2-pyridinyl CF 3 CH3 0 3-Cl, 5-CH 3 3-chloro-2-pyridinyl CF 3

CH

3 0 3-Cl, 5-CN 3-chloro-2-pyridinyl CF 3

CH

3 0 3-Br 3-chloro-2-pyridinyl CF 3 CH3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3 CH3 0 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3 CH3 0 3-Br, 5-I .3-chloro-2-pyridinyl CF 3 CH3 0 3-Br, 5-CH3 3-chloro-2-pyridinyl CF3 CH3 0 3-Br, 5-CN 3-chloro-2-pyridinyl CF3 CH3 0 3-I 3-chloro-2-pyridinyl CF3 0113 0 3-I, 5-Cl 3-chloro-2-pyridinyl OF 3 CH3 0 3-I, 5-Br 3-chloro-2-pyridinyl CF, CH3 0 3-I, 5-B 3-chloro-2-pyridinyl CF3 CH3 0 3-I, 5-013 3-chloro-2-pyridinyl CF3 CH3 0 3-I, 5-CN 3-chloro-2-pyridinyl CF3 189 Table 17 R_6 A 32 Ri) a

CH

3 0 3-CH 2

CH

3 3-chloro-2-pyridifyl

CF

3

CH

3 0 3-CH(CH 3

)

2 3-chloro-2-pyridinyl CF 3

CH

3 0 3-C(CH 3

)

3 3-chloro-2-pyridiyl

CF

3

CH

3 0 3-CF 3 3-chloro-2-pyridinyl CF 3

CH

3 0 30CH 3 3-chloro-2-pyridlnyl

CF

3

CH

3 0 3-phenyl 3-chloro-2-pyridinyl CF 3

CH

3 0 3-CH 2

CH

3 , 5-Cl 3-chloro-2-pyridinyl CF 3

CH

3 0 3-CH(CH 3

)

2 , 5-Cl 3-chloro-2-pyridinyl

CF

3

CH

3 0 3-C(CH 3

)

3 , 5-Cl 3-chloro-2-pyridinyl

CF

3

CH

3 0 3-CF 3 , 5-Cl 3-chloro-2-pyridinyl

CF

3

CH

3 0 3-0CH 3 , 5-Cl 3-chloro-2-pyridifyl

CF

3

CH

3 0 3-phenyl, 5-Cl 3-chloro-2-pyridifyl CF 3

CH

3 0 3-CM 3 , 4-Cl 3-chloro-2-pyridinyl CF 3

CH

3 0 3-Cl, 4-Cl 3-chloro-2-pyridiyl CF 3

CH

3 0 3-CH 3 , 6-Cl 3-chloro-2-pyridinyl

CF

3

CH

3 0 3-Cl, 6-Cl 3-chloro-2-pyridil

CF

3

CH

3 0 3-CM 3 , 4-C1, 5-Cl 3-chloro-2-pyridifyl CF 3

CH

3 0 3-Cl, 4-Cl, 5-Cl 3-chloro-2-pyridinyl

CF

3

CH

3 0 3-CH 3 , 5-Cl, 6-Cl 3-chloro-2-pyridinyl CF 3

CM

3 0 3-Cl, 5-Cl, 6-Cl 3-chloro-2-pyrdinyl CF 3

CH

3 0 3-CH 3 , 5-F 3-chloro-2-pyridinyl CF 3

CM

3 0 3-Cl, 5-F 3-chloro-2-pyridifyl CF 3

CM

3 0 3-Br, 5-F 3-chloro-2-pyriflyl CF 3

CH

3 0 3-1, 5-F 3-chloro-2-pyridifyl CF 3

CH

3 0 3-Me,4,5-CHCH-CHCH- 3-chloro-2-pyridinyl CF 3

CM

3 0 3-Cl,4,5-CMCM-CMCH- 3-chloro-2-pyridifyl CF 3

CM

3 10 3-Br,4,5-CHCH-CHCH- 3-chloro-2-pyridinyl CF 3

CM

3 0 3-I,4,5-CHCH-CMCH- 3-chloro-2-pyridinyl CF 3 ,190 Table 18

R

6

A

32 (R) Ra

CM

3 0 3-CH 3 3-Chloro-2-pyridinyl SCH3

CM

3 0 3-CH 3 , 5-Cl 3-choro-2-pyriinylSCH 3

CH

3 0 3-CH 3 , 5-Br 3-chloro-2-pyridinyl SCH3

CH

3 0 3-CH 3 , 5-I 3-chloro-2-pyridinyl SCH 3

CM

3 0 3-CH 3 , 5-CH 3 3-chloro-2-pyridinyl SCH 3

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl SCH3

CH

3 0 3-Cl 3-chloro-2-pyridinyl SCH3

CH

3 0 3-Cl, 5-Cl 3-chloro-2-pyridinyl SCH3

CH

3 0 3-Cl, 5-Br 3-chloro-2-pyridinyl SCH3

CH

3 0 3-Cl, 5-I 3-chloro-2-pyridinyl SCH3

CH

3 0 3-Cl, 5-CH 3 3-chloro-2-pyridinyl SCH3

CM

3 0 3-Cl, 5-CN 3-chloro-2-pyridinyl SCH3

CM

3 0 3-Br 3-chloro-2-pyridinyl SCH 3

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl SCH3

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl SCH3

CH

3 0 3-Br, 5-I 3-chloro-2-pyridinyl SCH3

CM

3 0 3-Br, 5-CH 3 3-chloro-2-pyridinyl SCH 3

CH

3 0 3-Br, 5-CN 3-chloro-2-pyridinyl SCH3

CH

3 0 3-I 3-chloro-2-pyridinyl SCM 3

CM

3 0 3-1, 5-Cl 3-chloro-2-pyrdinyl SCH3

CH

3 0 3-I, 5-Br 3-chloro-2-pyridinyl SCM 3

CH

3 0 3-I, 5-I 3-chloro-2-pyridinyl SCH3

CH

3 0 3-1, 5-CM 3 3-chloro-2-pyridinyl SCH 3

CM

3 0 3-1, 5-CN 3-chloro-2-pyridinyl SCH3 .191 Table 19

R

6

A

32

(R

4 )n Rl 3 a- R ia-1

CH

3 0 3-CH 3 3-chloro-2-pyridinyl S(=O)CH 3

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridiyl S(=0)CH 3

CH

3 0 3-CH 3 , 5-Br 3-chloro-2-pyridinyl S(=0)CH 3

CH

3 0 3-CH 3 , 5-1 3-chloro-2-pyridinyl S(=0)CH 3

CH

3 0 3-OH 3 , 5-CM 3 3-chloro-2-pyridinyl S(=0)CH 3

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl S(=0)CH 3

CH

3 0 3-Cl 3-chloro-2-pyridinyl S(=0)CH 3

CM

3 0 3-Cl, 5-Cl 3-chloro-2-pyridinyl S(=0)CH 3

OH

3 0 3-Cl, 5-Br 3-chloro-2-pyridinyl S(=0)CH 3

CH

3 0 3-Cl, 5-1 3-chloro-2-pyridinyl S(=O)CH 3

CM

3 0 3-Cl, 5-CM 3 3-chloro-2-pyridinyl S(=)0H 3

OH

3 0 3-Cl, 5-ON 3-chloro-2-pyridinyl S(0)CH 3

CH

3 0 3-Br 3-chloro-2-pyridinyl S(=0)CH 3

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl S(=0)CH3

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl S(=0)CH 3

CH

3 0 3-Br, 5-I 3-chloro-2-pyridinyl S(=0)CH 3

CH

3 0 3-Br, 5-H 3 3-chloro-2-pyridinyl S (=0) CH 3

CH

3 0 3-Br, 5-CN 3-chloro-2-pyridinyl S(=0)CH 3

CH

3 0 3-1 3-chloro-2-pyrdinyl S(=O)CH 3

CH

3 0 3-I, 5-Cl 3-chloro-2-pyriinyl S(=O)0H 3

CH

3 0 3-I, 5-Br 3-chloro-2-pyridinyl S(=0)CH 3

CH

3 0 3-I, 5-I 3-chloro-2-pyridinyl S(=0)CM 3

CH

3 0 3-I, 5-CH 3 3-chloro-2-pyridinyl S(=O)CM 3

CH

3 0 3-I, 5-CN 3-chloro-2-pyricLnyl S(=0)CH 3 .192 Table 20 R 6 A 32 (R') R 13 a- 1 R X 4 a

CH

3 0 3-CS 3 3-chloro-2-pyridfyl S(=0) 2

CH

3

CR

3 0 3-CR 3 , 5-Cl 3-chloro-2-pyridlflyl S (=0) 2

CH

3

CH

3 0 3-CR 3 , 5-Br 3-chloro-2-pyridifyl S(=O) 2

CH

3

CH

3 0 3-CR 3 , 5-1 3-chloro-2-pyridlfyl S(=) 2

CH

3

CH

3 10 3-CR 3 , 5-CR 3 3-chloro-2-pyrdinfyl S (=0) 2

CH

3

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridiyl

S(=O)

2

CH

3

CH

3 0 3-Cl 3-chloro-2-pyridifyl S (=0) 2

CH

3

CH

3 0 3-Cl, 5-Cl 3-chloro-2-pyrdifyl S(=0) 2

CH

3

CH

3 0 3-Cl, 5-Br 3-chloro-2-pyridfyl S(=0) 2

CH

3

CH

3 0 3-Cl, 5-1 3-chloro-2-pyridifyl S(=O) 2

CH

3

CH

3 0 3-Cl, 5-CH 3 3-chloro-2-pyrdifyl S(=0) 2

CH

3

CH

3 10 3-C1, 5-CN 3-chloro-2-pyridilyl S (=0) 2

CR

3

CH

3 0 3-Br 3-chloro-2-pyridinyl S(=0) 2

CH

3

CR

3 10 3-Br, 5-Cl 3-chloro-2-pyridiflyl S (=0) 2

CH

3

CR

3 10 3-Br, 5-Br 3-chloro-2-pyridinyl S (=0) 2

CH

3

CR

3 10 3-Br, 5-I 3-chloro-2-pyr3.dinyl S (=0) 2

CH

3

CR

3 10 3-Br, 5-CR 3 3-chloro-2-pyridiflyl S (=0) 2

CH

3 CH 3 10 3-Br, 5-CN 3-chloro-2-pyridiflyl S (=0) 2

CR

3

CH-

3 10 3-1 3-chloro-2-pyridiflyl S (=0) 2

CH

3

CR

3 0 3-I, 5-Cl 3-chloro-2-pyridiflyl S (=0) 2

CH

3

CR

3 0 3-I, -Br 3-chloro-2-pyridiflyl S (=0) 2

CR

3

CR

3 0 3-I, 5-I 3-chloro-2-pyridinyl S (=0) 2

CH

3

CH

3 0 3-I, 5-CR 3 3-chloro-2-pyr3.diflyl S (=0) 2

CH

3

C

3 0 3-I, 5-CN 3-chloro-2-pyridinyl S (=0) 2

CR

3 .193 Table 21

CH

3 0 3-OH 3 , 5-Cl 3-chloro-2-pyridifyl SCH 2

OH

3

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl

SH

2

CH

3

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridifyl SCH 2

CH

3

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridifyl SOH 2 OH3

CH

3 0 3-OH 3 , 5-Cl 3-chloro-2-pyridifyl SCH(CH 3

)

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl SCH(CH 3

)

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl SOH(0H 3

)

2

CH

3 0 3-OH 3 , 5-ON 3-chloro-2-pyridinyl SH(CH 3

)

2

OH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl 00H 3

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl O0H 3

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl 00H 3

CH

3 0 3-OH 3 , 5-ON 3-chloro-2-pyridinyl OCH 3

OH

3 0 3-OH 3 , 5-01 3-chloro-2-pyr3.dinyl OCH 2

CF

3

CH

3 0 3-Br, 5-01 3-chloro-2-pyridinyl OCH 2

CF

3

OH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl OCH 2

CF

3

OH

3 0 3-OH 3 , 5-ON 3-chloro-2-pyridinyl 00H 2

OF

3

OH

3 0 3-OH 3 , 5-01 3-chloro-2-pyridinyl OH 2

OH

3

CH

3 0 3-Br, 5-01 3-chloro-2-pyridifyl

CH

2

OH

3

OH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl OH 2

CH

3

OH

3 0 3-OH 3 , 5-ON 3-chloro-2-pyridiCyl 0H 2

CH

3

CH

3 0 3-OH 3 , 5-01 3-chloro-2-pyridiCyl OH (CH 3 ) 2

OH

3 0 3-Br, 5-01 3-chloro-2-pyridifyl CH(0H 3

)

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl CH(0H 3

)

2

OH

3 0 3-OH 3 , 5-ON 3-ch(oro-2-pyrCdiny OH(0H 3 ) 2

OH

3 0 3-OH 3 , 5-01 3-chloro-2-pyrCdinyl C(CH 3

)

3

OH

3 0 3-Br, 5-01 3-chloro-2-pyridinyl C(0H 3

)

3

OH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl C(0H 3

)

3

OH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyriftnyl C(0H 3

)

3

OH

3 0 3-OH 3 , 5-0N 3-chloro-2-pyridinyl ON

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl ON

OH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl ON

OH

3 10 3-OH 3 , 5-N 3-chloro-2-pyridinyl ON -194 Table 22

R

6

A

32 (R') R4 3 aR 14a-1

CH

3 0 3-CH 3 , 5-Cl 3-fluoro-2-pyridifyl H

CH

3 0 3-Br, 5-Cl 3-fluoro-2-pyridinyl H 083 0 3-Br, 5-Br 3-fluoro-2-pyridifyl H

CH

3 0 3-CH 3 , 5-CN 3-fluoro-2-pyridinyl H

CH

3 0 3-CH 3 , 5-Cl 3-fluoro-2-pyridCnyl l1 013 0 3-Br, 5-Cl 3-fluoro-2-pyridinyl Ci

CH

3 0 3-Br, 5-Br 3-'fluoro-2-pyridinyl C1

CH

3 0 3-Cl3, 5-CN 3-fluoro-2-pyridiyl 01

CH

3 0 3-CH 3 , 5-Cl 3-fluoro-2-pyridinyl Br

CH

3 0 3-Br, 5-Cl 3-fluoro-2-pyridinyl Br

CH

3 0 3-Br, 5-Br 3-fluoro-2-pyridinyl Br

CH

3 0 3-OH 3 , 5-CN 3-fluoro-2-pyridinyl Br

CH

3 0 3-CH 3 , 5-Cl 3-fluoro-2-pyridiny. CF 3

CH

3 0 3-Br, 5-Cl 3-fluoro-2-pyridCnyl OF 3

CH

3 0 3-Br, 5-Br 3-fluoro-2-pyridinyl CF 3

CH

3 0 3-OH 3 , 5-ON 3-fluoro-2-pyridinyl CF 3

CH

3 0 3-OH 3 , 5-01 3-bromo-2-pyridinyl H

CH

3 0 3-Br, 5-01 3-bromo-2-pyridinyl H

CH

3 0 3-Br, 5-Br 3-bromo-2-pyridinyl H

CH

3 0 3-OH 3 , 5-ON 3-bromo-2-pyridinyl H CH3 0 3-OH 3 , 5-Cl 3-bromo-2-pyridinyl Cl

CH

3 0 3-Br, 5-Cl 3-bromo-2-pyridinyl Cl

OH

3 0 3-Br, 5-Br 3-bromo-2-pyridinyl Cl CH3 0 3-OH 3 , 5-ON 3-bromo-2-pyridinyl Cl

CH

3 0 3-CH 3 , 5-Cl 3-bromo-2-pyridinyl Br CH3 0 3-Br, 5-Cl 3-bromo-2-pyridinyl Br

OH

3 0 3-Br, 5-Br 3-bromo-2-pyridinyl Br

CH

3 0 3-CH 3 , 5-CN 3-bromo-2-pyridinyl Br

OH

3 0 3-083, 5-01 3-bromo-2-pyridinyl CF 3 CH3 0 3-Br, 5-01 3-bromo-2-pyridinyl OF 3 083 0 3-Br, 5-Br 3-bromo-2-pyridlnyl CF 3 083 10 3-083, 5-ON 3-bromo-2-pyridinyl OF 3 195 Table 23 R6 32

(R

4 )n R1 3 al R_a

CH

3 0 3-CH 3 , 5-Cl 3-methyl-2-pyridifyl H

CH

3 0 3-Br, 5-Cl 3-methyl-2-pyridHyl H

CH

3 0 3-Br, 5-Br 3-methyl-2-pyridinyl H

CH

3 0 3-CH 3 , 5-CN 3-methyl-2-pyridnyl H

CH

3 0 3-CH 3 , 5-Cl 3-methyl-2-pyrCdinyl C1

CH

3 0 3-Br, 5-CC 3-methyl-2-pyrldnyl Cl

CH

3 0 3-Br, 5-Br 3-methyl-2-pyrCd1yl Cl

CH

3 0 3-CH 3 , 5-CN 3-methyl-2-pyridinyl Cl

CH

3 0 3-CH 3 , 5-Cl 3-methyl-2-pyridinyl Br

CH

3 0 3-Br, 5-Cl 3-methyl-2-pyrdinyl Br

CH

3 0 3-Br, 5-Br 3-methyl-2-pyridinyl Br

CH

3 0 3-CH 3 , 5-CN 3-methyl-2-pyridinyl Br

CH

3 0 3-CH 3 , 5-Cl 3-methyl-2-pyridinyl CF 3

CH

3 0 3-Br, 5-Cl 3-methyl-2-pyridinyl CF 3

CH

3 0 3-Br, 5-Br 3-methyl-2-pyridinyl CF 3

CH

3 0 3-CH 3 , 5-CN 3-methyl-2-pyridinyl CF 3

CH

3 0 3-CH 3 , 5-Cl 3-trifluoromethyl-2-pyridifyl H

CH

3 0 3-Br, 5-Cl 3-trifluoromethyl-2-pyridinyl H

CH

3 0 3-Br, 5-Br 3-trifluoromethyl-2-pyridinyl H

CH

3 0 3-CH 3 , 5-CN 3-trifluoromethyl-2-pyridinyl H

CH

3 0 3-CH 3 , 5-Cl 3-trCfluoromethyl-2-pyr1dinyl Cl

CH

3 0 3-Br, 5-Cl 3-trifluoromethyl-2-pyridinyl C1

CH

3 0 3-Br, 5-Br 3-trifluoromethyl-2-pyridiyl Cl

CH

3 0 3-CH 3 , 5-CN 3-trifluoromethyl-2-pyridinyl Cl

CH

3 0 3-CH 3 , 5-Cl 3-trifluoromethyl-2-pyridinyl Br

CH

3 0 3-Br, 5-Cl 3-trifluoromethyl-2-pyridnyl Br

CH

3 0 3-Br, 5-Br 3-trifluoromethyl-2-pyridinyl Br

CH

3 0 3-CH 3 , 5-CN 3-trifluoromethyl-2-pyridinyl Br

CH

3 0 3-CH 3 , 5-Cl 3-trifluoromethyl-2-pyridinyl CF 3

CH

3 0 3-Br, 5-Cl 3-trifluoromethyl-2-pyridinyl CF 3

CH

3 0 3-Br, 5-Br 3-trifluoromethyl-2-pyridinyl CF 3

CH

3 0 3-CH 3 , 5-CN 3-trifluoromethyl-2-pyrdinyl CF 3 196 Table 24

R

6

A

32 (R')n R14a-1

CH

3 0 3-CH 3 , 5-Cl 3-cyano-2-pyridinyl H

CH

3 0 3-Br, 5-Cl 3-cyano-2-pyridinyl H

CH

3 0 3-Br, 5-Br 3-cyano-2-pyridinyl H

CH

3 0 3-CH 3 , 5-CN 3-cyano-2-pyridifyl H

CH

3 0 3-CH 3 , 5-Cl, 3-cyano-2-pyridinyl C.

CH

3 0 3-Br, 5-Cl 3-cyano-2-pyrCd1nyl Cl

CH

3 0 3-Br, 5-Br 3-cyano-2-pyridifyl Cl

CH

3 0 3-CH 3 , 5-CN 3-cyano-2-pyridinyl Cl

CH

3 0 3-CH 3 , 5-Cl 3-cyano-2-pyridinyl Br

CH

3 0 3-Br, 5-Cl 3-cyano-2-pyridinyl Br

CM

3 0 3-Br, 5-Br 3-cyano-2-pyridinyl Br

CH

3 0 3-C 3 , 5-CN 3-cyano-2-pyridinyl Br

CH

3 0 3-CH3, 5-Cl 3-cyano-2-pyridlnyl CF 3

CH

3 0 3-Br, 5-Cl 3-cyano-2-pyridinyl CF 3

CH

3 0 3-Br, 5-Br 3-cyano-2-pyridinyl

CF

3

CH

3 0 3-CM 3 , 5-CN 3-cyano-2-pyridinyl

CF

3

CH

3 0 3-CM 3 , 5-Cl 3-nitro-2-pyridinyl H

CH

3 0 3-Br, 5-Cl 3-nitro-2-pyridinyl H

CH

3 0 3-Br, 5-Br 3-nitro-2-pyridiflyl H

CH

3 0 3-CH 3 , 5-CN 3-nltro-2-pyr-d3nyl H

CH

3 0 3-CH3, 5-Cl 3-nitro-2-pyridnyl Cl

CH

3 0 3-Br, 5-Cl 3-nitro-2-pyridiny1 Cl

CH

3 0 3-Br, 5-Br 3-nitro-2-pyridinyl Cl

CH

3 0 3-CM 3 , 5-CN 3-nitro-2-pyridiny 2.Cl

CH

3 0 3-CH 3 , 5-Cl 3-nitro-2-pyridinyl Br

CH

3 0 3-Br, 5-Cl 3-nitro-2-pyridinyl Br

CH

3 0 3-Br, 5-Br 3-nitro-2-pyridiflyl Br

CH

3 0 3-CH 3 , 5-CN 3-nltrc-2-pyri3.flyl Br

CM

3 0 3-CH 3 , 5-Cl 3-nitro-2-pyridinyl CF 3

CH

3 0 3-Br, 5-Cl 3-nitro-2-pyridinyl CF 3

CH

3 -0 3-Br, 5-Br 3-nitro-2-pyridinyl

CF

3

C

3 0 3-CH 3 , 5-CN 3-nitro-2-pyridinyl ,CF 3 ,197 Table 25

R

6

A

32

(R

4 )n

CH

3 0 3-CH 3 , 5-Cl 2-chorophenyl H

CH

3 0 3-Br, 5-Cl 2-chiorophenyl H

CH

3 0 3-Br, 5-Br 2-chlorophenyl H

CH

3 0 3-CH 3 , 5-CN 2-chiorophenyl H

CH

3 0 3-CH 3 , 5-Cl 2-chlorophenyl Cl

CH

3 0 3-Br, 5-Cl 2-chlorophenyl Cl

CH

3 0 C3-Br, 5-Br 2-chlorophenyl C

CH

3 0 3-CH 3 , 5-CN 2-chCorophenyl Cl

CH

3 0 3-CH 3 , 5-Cl 2-chlorophenyl Br

CH

3 0 3-Br, 5-Cl 2-chlorophenyl Br

CH

3 0 3-Br, 5-Br 2-chlorophenyl Br

CH

3 0 3-CH 3 , 5-CN 2-chlorophenyl Br

CH

3 0 3-CH 3 , 5-Cl 2-chlorophenyl CF 3

CH

3 0 3-Br, 5-Cl 2-chlorophenyl CF 3

CH

3 0 3-Br, 5-Br 2-chlorophenyl CF 3

CH

3 0 3-CH 3 , 5-CN 2-chlorophenyl CF 3

CH

3 0 3-CR 3 , 5-Cl 2,6-dichlorophenyl H

CH

3 0 3-Br, 5-Cl 2,6-dichiorophenyl H

CH

3 0 3-Br, 5-Br 2,6-dichlorophenyl H

CH

3 0 3-CH 3 , 5-CN 2,6-dichlorophenyl H

CH

3 0 3-CH 3 , 5-Cl 2,6-dichlorophenyl Cl

CH

3 0 3-Br, 5-Cl 2,6-dichlorophenyl Cl

CH

3 0 3-Br, 5-Br 2,6-dichlorophenyl C1

CH

3 0 3-CH 3 , 5-CN 2,6-dichlorophenyl Cl

CH

3 0 3-CR 3 , 5-Cl 2,6-dichlorophenyl Br

CH

3 0 3-Br, 5-Cl 2,6-dichlorophenyl Br

CH

3 0 3-Br, 5-Br 2,6-dichlorophenyl Br

CH

3 0 3-CM 3 , 5-CN 2,6-dichlorophenyl Br

CH

3 0 3-CH 3 , 5-Cl 2,6-dichlorophenyl CF 3

CH

3 0 3-Br, 5-Cl 2,6-dichlorophenyl CF 3

CH

3 0 3-Br, 5-Br 2,6-dichlorophenyl CF 3

CH

3 0 3-CH 3 , 5-CN 2,6-dichlorophenyl CF 3 -198 Table 26

R

6

A

32

(R

4 )R R14a

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl H

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Cl

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl Cl

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3

CH

2 CH 0 3-C 3 , 5-CN 3-chloro-2-pyridinyl CF 3 .199 Table 27

R

6

A

32 (R')R R 1-1

CH

2

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

CH

2

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H

CH

2

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl H

CH

2

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CH

2

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Cl

CH

2

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl

CH

2

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl Cl

CH

2

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridiryl Cl

CH

2

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br

CH

2

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br

CH

2

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br

CH

2

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br

CH

2

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3

CH

2

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3

CH

2

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3

CH

2

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl CF 3

CH(CH

3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

CH(CH

3

)

2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H CH (CH 3 ) 2 0 3-Br, 5-Br 3-chloro-2-pyridinyl H

CH(CH

3

)

2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CH(CH

3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl C1

CH(CH

3 ) 2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl

CH(CH

3 ) 2 0 3-Br, 5-Br 3-chloro-2-pyridinyl Cl

CH(CH

3

)

2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl

CH(CH

3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br

CH(CH

3 ) 2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br

CH(CH

3

)

2 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br Cl (CH 3

)

2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br

CH(CH

3

)

2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3

CH(CH

3

)

2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3

CH(CH

3

)

2 0 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3

CH(CH

3

)

2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl CF 3 200 Table 28 R 6 A 32

(R

4 )

R

1 4 a 1 C (CH 3 ) 3 0 3-CH 3 , 5-Cl 3-chloro2pyridifyl H C (CH 3 ) 3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl H C (CH 3 ) 3 0 13-Br, 5-Br 3-chloro-2-pyridinyl H C (CH 3 ) 3 0 3-CH 3 , 5-ON 3-chloro-2-pyridinyl H C (CH 3 ) 3 0 3-OH 3 , 5-Cl 3-chloro-2-pyridlinyl Cl C (CH 3 ) 3 0 3-Br, 5-Cl 3-chloro-2-pyriciinyl C1 C (CH 3 ) 3 0 3-Br, 5-Br 3-chloro-2-pyridiflyl Cl C (CH 3 ) 3 0 3-OH 3 , 5-CN 3-chloro-2-pyridinyl Cl C (CH 3 ) 3 0 3-OH 3 , 5-Cl__ 3-chloro-2-pyridilyl Br C (CH 3 ) 3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br C (CH 3 ) 3 0 3-Br, 5-Br 3-chloro-2-pyrid3.nyl Br C (CH 3 ) 3 -0 3-OH 3 , 5-ON 3-chloro-2-pyridiiyl Br

CO(CH

3 ) 3 0 3-OH 3 , 5-01 3-chloro-2-pyridinyl

CF

3 C (0H 3 ) 3 0 3-Br, 5-01 3-chloro-2-pyridilyl CF 3 C (CH 3 ) 3 0 3-Br, 5-Br 3-chloro-2-pyrid.nyl

OF

3 C (CH 3 ) 0 3-OH 3 , .5-CN 3-chloro-2-pyridinyl OF 3

OH

2

CH=CH

2 0 3-OH 3 , 5-Cl. 3-chloro-2-pyridinyl H

CH

2

CH=CH

2 0 3-Br, 5-Cl 3-chloro-2-pyridflyl H

CH

2

CH=CH

2 0 3-Br, 5-Br 3-chloro-2-pyridflyl H

OH

2

CH=CH

2 0 3-OH 3 , 5-ON 3-chloro-2-pyridilyl H

CH

2

CH=CH

2 0 3-OH 3 , 5-Cl 3-chloro-2-pyridlflyl C1

CH

2

CH=CH

2 0 3-Br, 5-Cl 3-chloro-2-pyridflyl C1

CH

2

CH=CH

2 0 3-Br, 5-Br 3-chloro-2-pyridflyl C1

CH

2

CH=CH

2 0 3-OH 3 , 5-ON 3-chloro-2-pyridilyl Cl

CH

2

CH=CH

2 0 3-OH 3 , 5-01 3-chloro-2-pyridilyl Br

CH

2

CH=CH

2 0 3-Br, 5-Cl 3-chloro-2-pyridrlyl Br

CH

2 OH=CH2 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br

CH

2

CH=CH

2 0 3-CH 3 , 5-ON 3-chloro-2-pyridilyl Br

CH

2 CH=0H 2 0 3-OH 3 , 5-Cl 3-chloro-2-pyridxflyl

CF

3

CH

2

OH=CH

2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3

CH

2

CH=CH

2 0 3-Br, 5-Br 3-chloro-2-pyridilyl

CF

3

CH

2

CH=CH

2 0 3-OH 3 , 5-ON 3-chloro-2-pyridinyl CF 3 201 Table 29 R6 A32 (R') R R1 4 a-1

CH

2 CCH 0 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl H

CH

2 CCH 0 3-Br, 5-Cl 3-chloro-2-pyrdifyl H

CH

2 CCH 0 3-Br, 5-Br 3-chloro-2-pyridifyl H

CH

2 CCH 0 3-CH 3 , 5-CN 3-chloro-2-pyridifyl H

CH

2 CCH 0 3-OH 3 , 5-Cl 3-chloro-2-pyrdinyJ Cl

CH

2 CCH 0 3-Br, 5-Cl 3-chloro-2-pyrdinyl Cl

CH

2 CCH 0 3-Br, 5-Br 3-chloro-2-pyridinyl Cl

CH

2 CCH 0 3-OH 3 , 5-ON 3-chloro-2-pyridinyl Cl

CH

2 CCH 0 3-Cl- 3 , 5-Cl 3-chloro-2-pyridiflyl Br

CH

2 CCH 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br

CH

2 CCH 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br

CH

2 CCH 0 3-OH 3 , 5-ON 3-chloro-2-pyridiyl Br

CH

2 CCH 0 3-OH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3

CH

2 CCH 0 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3

CH

2 CCH 0 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3

CH

2 CH' 0 3-CH 3 i 5-CN 3-chloro-2-pyridinyl CF 3 phenyl 0 3-OH 3 , 5-Cl 3-chloro-2-pyrdinyl H phenyl 0 3-Br, 5-Cl 3-chloro-2-pyrdinyl H phenyl 0 3-Br, 5-Br 3-chloro-2-pyridllyl H phenyl 0 3-OH 3 , 5-ON 3-chloro-2-pyridinyl H phenyl 0 3-03, 5-Cl 3-chloro-2-pyridinYl Cl phenyl 0 3-Br, 5-Cl 3-chloro-2-pyridiyl Cl phenyl 0 3-Br, 5-Br 3-chloro-2-pyridnyl Cl phenyl 0 3-CH 3 , 5-ON 3-chloro-2-pyridinyl Cl phenyl 0 3-OH 3 , 5-Cl 3-chloro-2-pyridil Br phenyl 0 3-Br, 5-Cl 3-chloro-2-pyrdinyl Br phenyl 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br phenyl 0 3-OH 3 , 5-ON 3-chloro-2-pyridilyl Br' phenyl 0 3-OH 3 , 5-Cl 3-chloro-2-pyridnyl CF 3 phenyl 0 3-Br, 5-Cl 3-chloro-2-pyridinyl OF 3 phenyl 0 3-Br, 5-Br 3-chloro-2-pyridiyl CF 3 phenyl O 3-CH 3 , 5-CN 3-chloro-2-pyridinyl OF 3 202 Table 30

A

32 (RR R 3 al

R

4 a-i

CH

3 S 3-CH 3 , 5-Cl 3-Chloro-2-pyrldlflyl H

CH

3 S 3-Br, 5-Cl 3-chloro-2-pyridifyl H

CH

3 S 3-Br, 5-Br 3-chloro-2-pyridl H

CH

3 S 3-CH 3 , 5-CN 3-chloro-2-pyridin-l H

CH

3 S 3-CH 3 , 5-Cl 3-chlor-2-pyr-d-y. C

CH

3 S 3-Br, 5-Cl 3-chloro-2-pyridifyl Cl

CH

3 S 3-Br, 5-Br 3-chloro-2-pyr-d---yl C

CH

3 S 3-CH 3 , 5-CN 3-chloro-2-pyridlflyl Cl

CH

3 S 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br

CH

3 S 3-Br, 5-Cl 3-chloro-2-pyridlflyl Br

CH

3 S 3-Br, 5-Br 3-chloro-2-pyridifyl Br

CH

3 3-CH 3 , 5-CN 3-chloro-2-pyrldlfYl Br

CH

3 S 3-CH 3 , 5-Cl 3-chloro-2-pyrBdrfyl

CF

3

CH

3 S 3-Br, 5-Cl 3-chloro-2-pyridifyl

CF

3

CH

3 S 3-Br, 5-Br 3-chloro-2-pyridlfYl

CF

3

CH

3 S 3-CH 3 , 5-CN 3-chloro-2-pyridinyl

CF

3

CH

2

CH

3 S 3-CH 3 , 5-Cl 3-chloro-2-pyrCdFfyl H

CH

2

CH

3 S 3-Br, 5-Cl 3-chloro-2-pyridinyl H

CH

2

CH

3 S 3-Br, 5-Br 3-chloro-2-pyridifYl H

CH

2

CH

3 S 3-Cl 3 , 5-CN 3-chloro-2-pyridifYl H

CH

2

CH

3 S 3-CH 3 , 5-Cl 3-chloro-2-pyrdinfYl Cl

CH

2

CH

3 S 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl

CH

2

CH

3 S 3-Br, 5-Br 3-chloro-2-pyridlflyl Cl

CH

2

CH

3 S 3-Cl 3 , 5-CN 3-chloro-2-pyridinfyl Cl

CH

2

CH

3 S 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl Br

CH

2

CH

3 S 3-Br, 5-Cl 3-chloro-2-pyraidlfyl Br

CH

2

CH

3 S 3-Br, 5-Br 3-chloro-2-pyrdinfyl Br

CH

2

CH

3 S 3-CH 3 , 5-CN 3-chloro-2-pyr.difyl -Br

CH

2

CH

3 S 3-CM 3 , 5-Cl 3-chloro-2-pyridflyl

CF

3

CH

2

CH

3 S 3-Br, 5-Cl 3-chloro-2-pyridinfyl

CF

3

CH

2

CH

3 S 3-Br, 5-Br 3-chloro-2-pyridinyl

CF

3

CH-

2

CH

3 S 3-Cl 3 , 5-CN 3-chloro-2-pyrdinfyl

CF

3 '203 Table 31

R

6

A

32 (R')

R

13 a-i R14a-1 phenyl S 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H phenyl S 3-Br, 5-Cl 3-chloro-2-pyridinyl H phenyl S 3-Br, 5-Br 3-chloro-2-pyridinyl H phenyl S 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H phenyl S 3-CH 3 , 5-Cl 3-chloro-2-pyridnyl Cl phenyl S 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl phenyl S 3-Br, 5-Br 3-chloro-2-pyrid.fyl Cl phenyl S 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl phenyl S 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br phenyl S 3-Br, 5-Cl 3-chloro-2-pyridinyl Br phenyl S 3-Br, 5-Br 3-chloro-2-pyridinyl Br phenyl S 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br phenyl S 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl

CF

3 phenyl S 3-Br, 5-Cl 3-chloro-2-pyridinyl

CF

3 phenyl S 3-Br, 5-Br 3-chloro-2-pyridinyl

CF

3 phenyl S 3-CH 3 , 5-CN 3-chloro-2-pyridinyl

CF

3 A compound represented by the formula (1-R): R 14a-1 N \CI 4 3 N,R (1-R) (R4)n |2 R I -- N---N--C-OCH3 6 2 3 5 wherein R', R 2 , R 3 , (R 4 )n and R14a-1 represent combinations shown in Table 32 to Table 39.

204 Table 32

RRR

3 R2R3_()_ R i-1 H CH 3 H 3-CH 3 , 5-Cl H H CH 3 H 3-Br, 5-Cl H H CH 3 H 3-Br, 5-Br H H CH 3 H 3-CH 3 , 5-CN H H CH 3 H 3-CH 3 , 5-Cl Cl H CH 3 H 3-Br, 5-Cl Cl H CH 3 H 3-Br, 5-Br Cl H CH 3 H 3-CH 3 , 5-CN Cl H CH 3 H 3-CH 3 , 5-Cl Br H CH 3 H 3-Br, 5-Cl Br H CH 3 H 3-Br, 5-Br Br H CH 3 H 3-CH 3 , 5-CN Br H CH 3 H 3-CH 3 , 5-Cl CF 3 H CH 3 H 3-Br, 5-Cl CF 3 H CH 3 H 3-Br, 5-Br CF 3 H CH 3 H 3-CH 3 , 5-CN CF 3 H H CH 3 3-CH 3 , 5-Cl H H H CH 3 3-Br, 5-Cl H H H CH 3 3-Br, 5-Br H H H CH 3 3-CH 3 , 5-CN H H H CH 3 3-CH 3 , 5-Cl C1 H H CH 3 3-Br, 5-Cl Cl H H CH 3 3-Br, 5-Br Cl H H CH 3 3-CH 3 , 5-CN Cl H H CH 3 3-CH 3 , 5-Cl Br H H CH 3 3-Br, 5-Cl Br H H CH 3 3-Br, 5-Br Br H H CH 3 3-CH 3 , 5-CN Br H H CH 3 3-CH 3 , 5-Cl CF 3 H H CH 3 3-Br, 5-Cl CF 3 H H CH 3 3-Br, 5-Br CF 3 H H CH 3 3-CH 3 , 5-CN CF 3 205 Table 33 R_

R

2 R 3

(R

4 ) R 1a-1 H CH 3

CH

3 3-CH 3 , 5-Cl H H CH 3 CH3 3-Br, 5-Cl H H CH 3 CH3 3-Br, 5-Br H H CH 3

CH

3 3-CH 3 , 5-CN H H CH 3 CH31 3-CH3, 5-Cl Cl H CH3 CH3 3-Br, 5-Cl Cl H CH 3

CH

3 3-Br, 5-Br Cl H CH 3

CH

3 3-CH 3 , 5-CN Cl H CH 3

CH

3 3-CH 3 , 5-Cl Br H CH3 CH 3 3-Br, 5-Cl Br H CH 3

CH

3 3-Br, 5-Br Br H CH 3

CH

3 3-CH 3 , 5-CN Br H CH 3

CH

3 3-CH 3 , 5-Cl CF 3 H CH 3

CH

3 3-Br, 5-Cl CF 3 H CH 3

CH

3 3-Br, 5-Br CF 3 H CH 3

CH

3 3-CH3, 5-CN CF 3 H H CH2CH3 3-CH 3 , 5-Cl H H H CH 2

CH

3 3-Br, 5-Cl H H H CH 2

CH

3 3-Br, 5-Br H H H CH2CH3 3-CH 3 , 5-CN H H H CH2CH3 3-CH 3 , 5-Cl Cl H H CH 2

CH

3 3-Br, 5-Cl Cl H H CH 2

CH

3 3-Br, 5-Br Cl H H CH2CH3 3-CH3, 5-CN Cl H H CH2CH3 3-CH3, 5-Cl Br H H CH2CH3 3-Br, 5-Cl Br H H CH2CH3 3-Br, 5-Br Br H H CH2CH3 3-CH3, 5-CN Br H H CH2CH3 3-CH3, 5-Cl CF 3 H H CH2CH3 3-Br, 5-Cl CF 3 H H CH2CH3 3-Br, 5-Br CF 3 H H CH2CH3 3-CH3, 5-CN CF 3 ,206 Table 34

RIR

2 R 3 (W),_______ R 1 4 a-1 H H CH(CH 3

)

2 3-OH 3 , 5-Cl H H H CH(CH 3

)

2 3-Br, 5-Cl H H H CH (CH 3

)

2 3-Br, 5-Br H H H CH (CH 3

)

2 3-OH 3 , 5-ON H H H CH (CH 3

)

2 3-CH 3 , 5-Cl C H H CH (CH 3

)

2 3-Br, 5-Cl Cl H H CH (CH 3

)

2 3-Br, 5-Br Cl H H CH (CH 3

)

2 3-CH 3 , 5-CN Cl H H CH (CH 3

)

2 3-CH 3 , 5-Cl Br H H CH (CH 3

)

2 3-Br, 5-Cl Br H H CH (CH 3 ) 2 3-Br, 5-Br Br H H CH (CH 3 ) 2 3-OH 3 , 5-N Br H H CH (CH 3

)

2 3-OH 3 , 5-Cl CF 3 H H CH (CH 3

)

2 3-Br, 5-01 CF 3 H H CH (CH 3 ) 2 3-Br, 5-Br CF 3 H H CH (CH 3 ) 2 3-OH 3 , 5-CN CF 3 H H CO(CH 3 ) 3 3-CH 3 , 5-Cl H H H C (CH 3 )3 3-Br, 5-Cl H H H C(CH 3

)

3 3-Br, 5-Br H H H C(CH 3

)

3 3-CM 3 , 5-CN H H H CO(CH 3 ) 3 3-CM 3 , 5-Cl Cl H H C (CH 3 ) 3 3-Br, 5-Cl 01 H H C(CH 3

)

3 3-Br, 5-Br 01 H H C (0H 3 ) 3 3-OH 3 , 5-CN Cl H H C (0H 3

)

3 3-CM 3 , 5-Cl Br H H CO(CH 3 ) 3 3-Br, 5-Cl Br H H CO(0H 3 ) 3 3-Br, 5-Br Br H H C (CH 3 ) 3 3-OH 3 , 5-ON_ Br H H C (CH 3

)

3 3-CH 3 , 5-Cl CF 3 H H C (0H 3 ) 3 3-Br, 5-Cl CF 3 H H CO(CH 3 ) 3 3-Br, 5-Br OF 3 H H C (CH 3 ) 3 3-CM 3 , 5-CM CF 3 '207 Table 35 R1R2R3( ) R14 H HC (=0) OCH 3 3-CH 3 , 5-Cl H H H C (=O) OCH 3 3-Br, 5-Cl H H H C (=O) OCH 3 3-Br, 5-Br H H H C (=O) OCH 3 3-CH 3 , 5-CN H H H C (=O) OCH 3 3-CH 3 , 5-Cl Cl H H C (=0) OCH 3 3-Br, 5-Cl Cl H H C (=O) OCH 3 3-Br, 5-Br Cl H H C (=O) OCH 3 3-CH 3 , 5-CN Cl H H C (=O) OCH 3 3-CH 3 , 5-Cl Br H H C (=O) OCH 3 3-Br, 5-Cl Br H Hi C(=O) OCH 3 3-Br, 5-Br Br H H C (=O) OCH 3 3-CH 3 , 5-CN Br H H C (=O) OCH 3 3-CH 3 , 5-Cl CF 3 H -H C (=0)OCH 3 3-Br, 5-Cl CF 3 H H C (=O) OCH 3 3-Br, 5-Br CF 3 H H C (=O) OCH 3 3-CH 3 1 5-CN C F 3 H H C (=O) N(CH 3 ) 2 3-CH 3 , 5-Cl H H H C (=O) N(CH 3 ) 2 3-Br, 5-Cl H H H C (=O) N(CH 3 ) 2 3-Br, 5-Br H H H C (=O) N(CH 3 ) 2 3-CH 3 , 5-CN H H H C (=O) N(CH 3 ) 2 3-CH 3 , 5-Cl Cl H H C (=O) N(CH 3 ) 2 3-Br, 5-Cl Cl H H C (=O) N(CH 3

)

2 3-Br, 5-Br Cl H H C (=O) N(CH 3 ) 2 3-CH 3 , 5-CN Cl H H C (=O) N(CH 3 ) 2 3-CH 3 , 5-Cl Br H H C (=O) N(CH 3 ) 2 3-Br, 5-Cl Br H H C (=O) N(CH 3 ) 2 3-Br, 5-Br Br H H c (=O) N(CH 3 ) 2 3-CH 3 , 5-CN Br H H C (=O) N(CH 3 ) 2 3-CH 3 , 5-Cl CF 3 Hi H C (=O) N(CH 3 ) 2 3-Br, 5-Cl CF 3 H H C (=0)N(CH1 3

)

2 3-Br, 5-Br CF, H H C (=0)N(CH1 3 ) 2 3-CH 3 , 5-CN CF 3 '208 Table 36 R R 2 R 3 (' 4

CH

3

CH

3 H 3 -CH 3 , 5-Cl H

CH

3

CH

3 H 3-Br, 5-Cl H

CH

3

CH

3 H 3-Br, 5-Br H

CH

3

CH

3 H 3-CH 3 , 5-CN H

CH

3

CH

3 H 3-CM 3 , 5-Cl C 1

CH

3

CH

3 H 3-Br, 5-Cl C 1

CH

3

CH

3 H 3-Br, 5-Br Cl1

CH

3

CM

3 H 3-CM 3 , 5-CN Cl1

CH

3

CM

3 H 3-CM 3 , 5-Cl Br

CH

3

CM

3 H 3 -Br, 5-Cl Br

CH

3

CM

3 H 3 -Br, 5-Br Br

CH

3

CM

3 H 3-CM 3 , 5-CN Br

CH

3

CH

3 H 3-CM 3 , 5-Cl CF 3

CH

3

CH

3 H 3 -Br, 5-Cl CF 3

CH

3

CM

3 H 3-Br, 5-Br CF 3

CH

3 * CH 3 H 3-CM 3 , 5-CN CF 3

CH

3 H CM 3 3-CM 3 , 5-Cl H

CH

3 H CH 3 3-Br, 5-Cl H

CH

3 H CM 3 3-Br, 5-Br H

CH

3 H CM 3 3-CM 3 , 5-CN H

CC

3 H CC 3 3l-CM 3 5-Cl Cl

CH

3 H CM 3 3-Br, 5-Cl C

CH

3 H CM 3 3-Br, 5-Br C

CC

3 H CM 3 3-CM 3 , 5-CN Cl

CM

3 H CM 3 3-CH 3 , 5-Cl Br

CH

3 H CH 3 3-Br, 5-Cl Br

CM

3 H CH 3 3-Br, 5-Br Br

CH

3 H CM 3 3-CM 3 , 5-CN Br

CH

3 H CH 3 3-CH 3 , 5-Cl CF 3

CH

3 H CH 3 3-Br, 5-Cl CF 3

CH

3 H CH 3 3-Br, 5-Br CF 3

CH

3 H CH 3 3-CM 3 , 5-CN CF 3 -209 Table 37 R_ _ R 2

R

3

R

4 a-l

CH

3

CH

3

CH

3 3-CM 3 , 5-Cl H

CH

3

CH

3

CM

3 3-Br, 5-Cl H

CM

3

CM

3

CH

3 3-Br, 5-Br H

CH

3

CH

3

CH

3 3-CM 3 , 5-CN H

CM

3

CH

3

CH

3 3-CM 3 , 5-Cl Cl

CH

3

CH

3

CH

3 3-Br, 5-Cl CF

CM

3

CM

3

CH

3 3-Br, 5-Br C

CH

3

CH

3

CH

3 3-CH 3 , 5-CN Cl

CH

3

CM

3

CM

3 3-CH 3 , 5-Cl Br

CM

3

CH

3

CH

3 3-Br, 5-Cl Br

CH

3

C

3

CH

3 3-Br, 5-Br Br

CM

3

CM

3

CH

3 3-CM 3 , 5-CN Br

CH

3

CH

3

CH

3 3-CH 3 , 5-Cl CF 3

CH

3 - CM 3

CM

3 3-Br, 5-Cl CF 3

CM

3

CM

3

CM

3 3-Br, 5-Br CF 3

CM

3

CM

3

CH

3 3-CM 3 , 5-CN CF 3

CM

3 H CH 2

CH

3 .3-CH 3 , 5-Cl H

CM

3 H

CH

2

CH

3 , 3-Br, 5-Cl Ii

CH

3 H CH 2

CH

3 3-Br, 5-Br H

CM

3 H CM 2

CH

3 3-CM 3 , 5-CN H

CH

3 H

CH

2

CH

3 3-CM 3 , 5-Cl Cl1

CH

3 H

CM

2

CM

3 3-Br, 5-Cl Cl1

CH

3 H CH 2

CM

3 3-Br, 5-Br Cl1

CM

3 H

CH

2

CM

3 3-CM 3 , 5-CN Cl1

CM

3 H CH 2

CM

3 3-CH 3 , 5-Cl Br

CH

3 H CH 2

CH

3 3-Br, 5-Cl Br

CM

3 M CH 2

CH

3 3-Br, 5-Br Br

CM

3 H CH 2

CM

3 3-CM 3 , 5-CN B r

CM

3 H CM 2

CH

3 3-CM 3 , 5-Cl CF 3

CM

3 H CH 2

CM

3 3-Br, 5-Cl CF 3

CH

3 H CM 2

CH

3 3-Br, 5-Br CF,

CM

3 H CH 2

CH

3 3-CH 3 , 5-CN _CF 3 210 Table 38 H

(R(

4 C RH

CH

3 HCH (CH 3

)

2 3-CH 3 , 5-Cl H

OH

3 H CH (CH 3

)

2 3-Br, 5-Cl H

CH

3 H CH (CH 3

)

2 3-Br, 5-Br H

OH

3 H CH (CH 3

)

2 3-OH 3 , 5-CN H

OH

3 H CH (CH 3

)

2 3-OH 3 , 5-Cl 01

OH

3 H CH (CH 3 ) 2 3-Br, 5-Cl Cl

CH

3 H CH (CH 3

)

2 3-Br, 5-Br 1

OH

3 H CH (CH 3

)

2 3-CH 3 , 5-ON 1

CH

3 H CH (CH 3

)

2 3-CH 3 , 5-Cl Br

CH

3 H CH (CH 3 ) 2 3-Br, 5-Cl Br

CH

3 H CH (CH 3 ) 2 3-Br, 5-Br Br

CH

3 H CH (CH 3 ) 2 3-OH 3 , 5-CN Br

OH

3 H CH (0H 3 ) 2 3-OH 3 , 5-01 OF 3

OH

3 H CH (CH 3 ) 2 3-Br, 5-01 CF 3 0113 H CH (CH 3 ) 3-Br, 5-Br OF 3

OH

3 H CH (CH 3 ) 2 3-OH 3 , 5-ON CF 3

OH

3 H C (CH3) 3 3-OH 3 , 5-Cl H

OH

3 H O (0H 3 ) 3 3-Br, 5-01 H

OH

3 * H O (0H3) 3 3-Br, 5-Br H

CH

3 H C0(013) 3 3-OH 3 , 5-ON H

OH

3 H O (CH 3 ) 3 3-OH 3 , 5-01 01

OH

3 H C CH 3 ) 3 3-Br, 5-01 01

CH

3 H CO(0H 3 ) 3 3-Br, 5-Br Cl

OH

3 H C (0H 3 ) 3 3-OH 3 , 5-ON 01

OH

3 H C (0H 3 ) 3 3-OH 3 , 5-Cl Br

OH

3 H CO(0H 3 ) 3 3-Br, 5-01 Br

OH

3 H CO(0H 3 ) 3 3-Br, 5-Br Br

OH

3 H C (CH 3 ) 3 3-OH.

3 , 5-ON Br

OH

3 H 0 (OH 3 ) 3 3-OH 3 , 5-01 OF 3 083 H C (0H 3 ) 3 3-Br, 5-Cl OF 3

OH

3 H O (0HD) 3 3-Br, 5-Br CF 3

OH

3 H C0(013) 3 3-OH 3 , 5-ON OF 3 211 Table 39 R R 2 R 3 (' 4

OH

3 H C(=O)OCH 3 3-CH 3 , 5-Cl H

CH

3 H C (=O) OCH 3 3-Br, 5-Cl H

OH

3 H C (=0) OCH 3 3-Br, 5-Br H

OH

3 H C (=0) OCH 3 3-CH 3 , 5-CN H

OH

3 H C (=O)00CH 3 3 -OH 3 , 5-Cl 01

CH

3 C (=0) OCH 3 3-Br, 5-Cl Cl

CH

3 HC (=O) OCH 3 3-Br, 5-Br Cl

OH

3 H C(=O)OCH 3 3-OH 3 , 5-ON Cl

OH

3 H C (=O)0CH 3 3-OH 3 , 5-Cl Br

CH

3 H C(=O)00H 3 3-Br, 5-01 Br

OH

3 H C(=O)OCH 3 3-Br, 5-Br Br

OH

3 H C (=O)0CH 3 3-OH 3 , 5-ON Br

OH

3 H C (=0) OCH 3 3-OH 3 , 5- CF 3

OH

3 H C(=O)OCH 3 3-Br, 5-01 OF 3

CH

3 HC (=) OCH 3 3-Br, 5-Br OF 3

OH

3 H C(=O)OCH 3 3-CH 3 H 5-ON OF 3

OH

3 H C(=O)N(0HD) 2 3-CH 3 , 5-Cl H

CH

3 H CO(=O) N (0HA 2 3-Br,. 5-01 H

OH

3 H C (=O) N (H 3 ) 2 3-Br, 5-Br H

CH

3 C (=O) N (CH 3

)

2 3-OH 3 , 5-ON H

OH

3 H CO(=O) N (H 3 ) 2 3-OH 3 , 5-Cl 01

OH

3 H CO(=O) N (0HA 2 3-Br, 5-01 01

OH

3 H CO(=O) N (H 3 ) 2 3-Br, 5-Br Cl

CH

3 H CO(=O) N (H 3 ) 2 3-OH 3 , 5-ON 01

OH

3 H C (=O) N (0HA 2 3-OH 3 , 5-Cl Br

OH

3 H CO(=O) N (0HA 2 3-Br, 5-01 Br

CH

3 H C(=O)N(0H 3

)

2 3-Br, 5-Br Br

OH

3 H CO(=O) N (H 3 ) 2 3-OH 3 , 5-ON Br

CH

3 H C(=O)N(0HA) 2 3-OH 3 , 5-01 OF 3

OH

3 H CO(=O) N (H 3 ) 2 3-Br, 5-01 OF 3

CH

3 H C(=O)N(0HD) 2 3-Br, 5-Br OF 3

CH

3 H C(=O)N(CH 3

)

2 3-OH 3 , 5-ON OF 3 212 Table 39 continued R 2 R3(R_),_

R

4 a-I H CH 3 H 3-Cl, 5-Cl H H CH 3 H 3-Cl, 5-Cl Cl H CH 3 H 3-Cl, 5-Cl Br H CH 3 H 3-Cl, 5-Cl CF 3 H H CH 3 3-Cl, 5-Cl H H H CH 3 3-Cl, 5-Cl Cl H H CH 3 3-Cl, 5-Cl Br H H CH 3 3-Cl, 5-Cl CF 3 H CH 3

CH

3 3-Cl, 5-Cl H H CH 3

CH

3 3-Cl, 5-Cl Cl H CH 3

CH

3 3-Cl, 5-Cl Br H CH 3

CH

3 3-Cl, 5-Cl CF 3 H H CH 2

CH

3 3-Cl, 5-Cl H H H CH 2

CH

3 3-Cl, 5-Cl Cl H H CH 2

CH

3 3-Cl, 5-Cl Br H H CH 2

CH

3 3-Cl, 5-Cl CF 3 H H CH (CH 3 ) 2 3-Cl, 5-Cl H H H CH (CH 3 ) 2 3-Cl, 5-Cl Cl H H ICH (CH 3 ) 2 3-Cl, 5-Cl Br H H CH (CH 3 ) 2 3-Cl, 5-Cl CF 3 H H C (CH 3 ) 3 3-Cl, 5-Cl H H H C (CH 3 ) 3 3-Cl, 5-Cl Cl H H C (CH 3 ) 3 3-Cl, 5-Cl Br H H C (CH 3 ) 3 3-Cl, 5-Cl CF 3 H H C(=O)OCH 3 3-Cl, 5-Cl H H H C(=O)OCH 3 3-Cl, 5-Cl Cl H H C(0)OCH 3 3-C1, 5-Cl Br H H C(=O)OCH 3 3-Cl, 5-Cl CF 3 H H C (=O) N(CH 3 ) 2 3-Cl, 5-Cl H H H C (=O) N(CH 3 ) 2 3-Cl, 5-Cl Cl H H C (=O) N(CH 3 ) 2 3-Cl, 5-Cl IBr H IH C (=O) N(CH 3 ) 2 3-Cl, 5-Cl ICF 3 213 Table 39 continued R 2 3 14-I

CH

3

CH

3 H 3-Cl, 5-Cl H

CH

3

CH

3 H 3-Cl, 5-Cl Cl

CH

3

CH

3 H 3-Cl, 5-Cl Br

CH

3

CH

3 H 3-Cl, 5-Cl CF 3

CH

3 H CH 3 I3-Cl, 5-Cl H

CH

3 H CH 3 3-Cl, 5-Cl Cl

CH

3 H C 3 3-Cl, 5-Cl Br

CH

3 H CH 3 3-Cl, 5-Cl CF 3

CH

3

CH

3

CH

3 3-Cl, 5-Cl H

CH

3 CH3 CH 3 3-Cl, 5-Cl Cl

CH

3

CH

3

CH

3 3-Cl, 5-Cl Br

CH

3

CH

3

CH

3 3-Cl, 5-Cl CF 3

CM

3 H CH 2

CH

3 3-Cl, 5-Cl H

CH

3 H CH 2

CH

3 3-Cl, 5-Cl Cl

CH

3 H CH 2

CH

3 3-Cl, 5-Cl Br

CH

3 H CH 2

CH

3 3-Cl, 5-Cl CF 3

CH

3 H CH(CH 3

)

2 3-Cl, 5-Cl H

CH

3 H CH (CH 3

)

2 3-Cl, 5-Cl Cl

CM

3 H CH (CH 3 ) z 3-Cl, 5-Cl Br

CH

3 H CH(CH 3

)

2 3-Cl, 5-Cl CF 3

CM

3 H C (CH 3 ) 3 3-Cl, 5-Cl H

CM

3 H C (CH 3 ) 3 3-Cl, 5-Cl Cl

CM

3 H C (CH 3 ) 3 3-Cl, 5-Cl Br

CM

3 H C (CH 3 ) 3 3-Cl, 5-Cl CF 3

CH

3 H C (=O)0OCH 3 3-Cl, 5-Cl H

CM

3 H C (=O) OCH 3 3-Cl, 5-Cl Cl

CM

3 H C (=O) OCH 3 3-Cl,' 5-Cl Br

CH

3 H C (=O) OCH 3 3-Cl, 5-Cl CF 3

CH

3 H C (=O) N(CM 3 ) 3-Cl, 5-Cl H

CM

3 H C (=O) N(CH 3 ) 2 3-Cl, 5-Cl Cl

CM

3 Hi C(=O) N(CM 3 ) 2 3-Cl, 5-Cl Br

CH

3 IH C (=O) N(CH 3 ) 2 3-Cl, 5-Cl CF 3 '214 Table 39 continued R1 R R 3 (R')

R'

4 a-1 H CH 3

CH

2

CH

3 3-CH 3 , 5-Cl H H CH 3

CH

2

CH

3 3-Br, 5-Cl H H CH 3

CH

2

CH

3 3-Br, 5-Br H H CH 3

CH

2

CH

3 3-CH 3 C 5-CN H H CH 3

CH

2

CH

3 3-Cl, 5-Cl H H CH 3

CH

2

CH

3 3-CH 3 , 5-Cl Cl H CH 3

CH

2

CH

3 3-Br, 5-Cl Cl H CH 3

CH

2

CH

3 3-Br, 5-Br Cl H CH 3

CH

2

CH

3 3-CH 3 , 5-CN C1 H CH 3

CH

2

CH

3 3-Cl, 5-Cl C). H CH 3

CH

2

CH

3 3-CH 3 , 5-Cl Br H CH 3

CH

2

CH

3 3-Br, 5-Cl Br H CH 3

CH

2

CH

3 3-Br, 5-Br Br H CH 3

CH

2

CH

3 3-CH 3 , 5-CN Br H CH 3

CH

2

CH

3 3-Cl, 5-Cl Br H CH 3

CH

2

CH

3 3-CH 3 , 5-Cl CF 3 H CH 3

CH

2

CH

3 3-Br, 5-Cl CF 3 H CH 3

CH

2

CH

3 3-Br, 5-Br CF 3 H CH 3

ICH

2

CH

3 3-CH 3 , 5-CN CF 3 H CH 3

CH

2

CH

3 3C,5C F ,215 Table 39 continued

R

1

R

2

R

3 (W), R14a-i H CH 3

CH(CH

3

)

2 3-CH 3 , 5-Cl H H CH 3

CH(CHA)

2 3-Br, 5-Cl H H CH 3

CH(CH

3 ) 2 3-Br, 5-Br H H CH 3

CH(CH

3 ) 2 3-CH 3 , 5-CN H H CH 3

CH(CH

3 ) 2 3-Cl, 5-Cl H H CH 3

CH(CH

3

)

2 3-CH 3 , 5-Cl Cl H CH 3

CH(CH

3 ) 2 3-Br, 5-Cl Cl H CH 3

CH(CH

3 ) 2 3-Br, 5-Br Cl H CH 3

CH(CH

3

)

2 3-CH 3 , 5-CN Cl H CH 3 CH (CH 3 ) 2 3-Cl, 5-Cl Cl i CH 3

CH(CH

3 ) 2 3-CH 3 , 5-Cl Br H CH 3

CH(CH

3 ) 2 3-Br, 5-Cl Br H CH 3

CH(CH

3 ) 2 3-Br, 5-Br Br H CH 3

CH(CH

3 ) 2 3-CH 3 5-CN Br H CH 3

CH(CHA)

2 3-Cl, 5-Cl Br H CH 3

CH(CH

3

)

2 3-CH 3 , 5-Cl CF 3 H CH 3

CH(CH

3 ) 2 .3-Br, 5-Cl CF 3 H CH 3

CH(CH

3 ) 2 3-Br, 5-Br CF 3 H CH 3 CH (CH 3 ) 2 3-CH 3 , 5-CN CF, 216 Table 39 continued R R2 R 3

(R

4 )n_ Ria-i H CH 2

CH

3

CH

3 3-CH 3 , 5-Cl H H CH 2

CH

3

CH

3 3-Br, 5-Cl H H CH 2

CH

3

CH

3 3-Br, 5-Br H H CH 2

CH

3

CH

3 3-CH3, 5-CN H H CH 2

CH

3

CH

3 3-C1, 5-Cl H H CH 2

CH

3

CH

3 3-CH 3 , 5-Cl Cl H CH 2

CH

3

CH

3 3-Br, 5-Cl Cl H CH 2

CH

3

CH

3 3-Br, 5-Br Cl H CH 2

CH

3

CH

3 3-CH 3 , 5-CN Cl H CH 2

CH

3

CH

3 3-Cl, 5-Cl C1 H CH 2

CH

3

CH

3 3-CH 3 , 5-Cl Br H CH 2

CH

3

CH

3 3-Br, 5-Cl Br H CH 2

CH

3

CH

3 3-Br, 5-Br Br H CH 2

CH

3

CH

3 3-CH 3 , 5-CN Br H CH 2

CH

3

CH

3 3-Cl, 5-Cl Br H CH 2

CH

3

CH

3 3-CH 3 , 5-Cl CF 3 H CH 2

CH

3

CH

3 3-Br, 5-Cl CF 3 H CH 2

CH

3

CH

3 3-Br, 5-Br CF 3 H CH 2

CH

3

CH

3 3-CH 3 , 5-CN CF 3 H CH 2

CH

3

CH

3 3-Cl, 5-Cl CF 3 217 Table 39 continued RR2R 3

(R_)._____

H CH(CH 3 ) 2

CH

3 3-CH 3 , 5-Cl H H CH(CH 3 ) 2

CH

3 3-Br, 5-Cl H H CH(CH 3 )2 C 3 3-Br, 5-Br H H CH (CH 3 ) 2

CH

3 3-Cl 3 , 5-CN H H CH(C1 3 ) 2

CH

3 3-Cl, 5-Cl H H CH(CH 3

)

2

CH

3 3-Cl 3 , 5-Cl Cl H CH(CH 3 ) 2

CH

3 3-Br, 5-Cl Cl H CH (CH 3

)

2 Cl 3 3-Br, 5-Br Cl H CH(CH 3 ) 2

CH

3 3-CH 3 , 5-CN Cl HCH(C1 3 2 l 3-Cl, 5-Cl Cl 3) CH3 H CH(CH 3 ) 2

CH

3 3-Cl 3 , 5-Cl Br H CI(C1 3 ) 2 Cl 3 3-Br, 5-Cl Br H CH(C1 3 ) 2

CH

3 3-Br, 5-Br Br H CH(CH 3 ) 2 Cl 3 3-Cl 3 , 5-CN Br H CI(CH 3 ) 2 Cl 3 3-Cl, 5-Cl Br H CH(CH 3 ) 2 Cl 3 3-Cl 3 , 5-Cl CF 3 H CI(CH 3 ) 2 Cl 3 3-Br, 5-Cl CF 3 H CH(CH 3

)

2

CH

3 3-Br, 5-Br CF 3 H CH (CH 3 ) 2

CH

3 3-Cl 3 , 5-CN CF 3

HCH(CH

3

)

2

CH

3 --- 3-Cl, 5-Cl JCF 3 '218 Table 39 continued R

R

3 R14a-1 H CH 2

CH

3

CH

2

CH

3 3-CH 3 , 5-Cl H H CH 2

CH

3

CH

2

CH

3 3-Br, 5-C) H H CH 2

CH

3

CH

2

CH

3 3-Br, 5-Br H H CH 2

CH

3

CH

2

CH

3 3-CH 3 , 5-CN H H CH 2

CH

3

CH

2

CH

3 3-Cl, 5-Cl H H CH 2

CH

3

CH

2

CH

3 3-CH 3 , 5-Cl Cl H CH 2

CH

3

CH

2

CH

3 3-Br, 5-Cl C1 H CH 2

CH

3

CH

2

CH

3 3-Br, 5-Br Cl H CH 2

CH

3

CH

2

CH

3 3-CH 3 , 5-CN Cl H CH 2

CH

3

CH

2

CH

3 3-Cl, 5-Cl Cl H CH 2

CH

3

CH

2

CH

3 3-CH 3 , 5-Cl Br H CH 2

CH

3

CH

2

CH

3 3-Br, 5-Cl Br H CH 2 CH3 CH 2

CH

3 3-Br, 5-Br Br H CH 2

CH

3

CH

2

CH

3 3-CH 3 , 5-CN Br H CH 2

CH

3

CH

2

CH

3 3-Cl, 5-Cl Br H CH 2

CH

3

CH

2

CH

3 3-CH 3 , 5-Cl CF 3 H CH 2

CH

3

CH

2

CH

3 3-Br, 5-Cl CF 3 H CH 2

CH

3

CH

2

CH

3 3-Br, 5-Br CF 3 H CH 2

CH

3

CH

2

CH

3 3-CH 3 , 5-CN CF 3 H CH 2

CH

3

CH

2

CH

3 3-Cl, 5-Cl CF 3 219 A compound represented by the formula (1-C): R14a-1 4 3 N 13-1 (1-C) (Rk - |n H-NH- -SR' 6 11 1 3 0 A wherein R 7 , A33, (R 4 )n, Ri 3 a-1 and Ri 4 a-1 represent combinations shown in Table 40 to Table 41.

,220 Table 40 R 7 A___ 33___(R___)____________ R1 4 al

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinfyl H

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridifyl H

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridlflyl H

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridifyl H

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinfll Cl

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinryl Cl

CM

3 0 3-Br, 5-Br 3-cloro-2-pyrdifyl Cl

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridlflyl Cl

CH

3 0 3-CM 3 , 5-Cl 3-chloro-2-pyridinfyl- Br

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridflyl Br

CH

3 0 3-Br, 5-Br 3-chloro-2-pyrdinfyl Br

CM

3 0 3-CM 3 , 5-CN 3-chloro-2-pyridinl Br

CM

3 0 3-CM 3 , 5-Cl 3-chloro-2-pyrldlrlyl

CF

3

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinfyl

CF

3

CH

3 0 3-Br, 5-Br 3-chloro-2-pyrdinfyl

CF

3

CH

3 0 3-CM 3 , 5-CN 3-chloro-2-pyridlflyl

CF

3

CH

2

CH

3 0 3-CM 3 , 5-Cl 3-chloro-2-pyrdinfyl H

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyrdinfyl H

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyr3-diflyl H

CH

2

CH

3 0 3-CM 3 , 5-CN 3-chloro-2-pyr3-dlfyl H

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl Cl

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyillnfyl Cl

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl C1

CH

2

CH

3 0 3-CM 3 , 5-CN 3-chloro-2-pyridinfyl Cl

CH

2

CH

3 0 3-CM 3 , 5-Cl 3-chloro-2-pyridlrlyl Br

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyr3.dlfyl Br

CH

2

CH

3 0 3-Br, 5-Br 3-chloro--2-pyridlflyl Br

CH

2

CH

3 0 3-CM 3 , 5-CN 3-chloro-2-pyridlflyl Br

CH

2

CH

3 0 3-CM 3 , 5-Cl 3-chloro-2-pyridiflyl

CF

3

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl

CF

3

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinlyl

CF

3

CH

2

CH

3 0 3-CH 3 , 5-CN 13-chloro-2-pyr3-dlfyl_!CF 3 '221 Table 41 RI_____ _ _A_33 (R 4 ) R R 3 a-l R pheny1 0 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl H phenyl 0 3-Br, 5-Cl 3-chloro-2-pyrdifyl H phenyl 0 3-Br, 5-Br 3-chloro-2-pyridinyl H phenyl 0 3-CH 3 , 5-CN 3-chloro-2-pyridflyl H phenyl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl Cl phenyl 0 3-Br, 5-Cl 3-chloro-2-pyridflyl C1 phenyl 0 3-Br, 5-Br 3-chloro-2-pyridlflyl Cl phenyl 0 3-CH 3 , 5-CN 3-chloro-2-pyrdinfyl Cl pheny1 0 3-CH 3 , 5-Cl 3-chloro-2-pyrEdElyl Br phenyl 0 3-Br, 5-Cl 3-chloro-2-pyridflyl Br phenyl 0 3-Br, 5-Br 3-chloro-2-pyr-dilyl -Br phenyl 0 3-CH 3 , 5-CN 3-chloro-2-pyridflYl Br phenyl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl-

CF

3 phenyl 0 3-Br, 5-Cl 3-chloro-2-pyr-dllyl

CF

3 phenyl 0 3-Br, 5-Br 3-chloro-2-pyrdinyl

CF

3 phenyl 0 3-CH 3 , 5-CN 3-chloro-2-pyr-dllyl

CF

3 phenyl S 3-CH 3 , 5-Cl ,3-chloro-2-pyri.dinlyl H phenyl S 3-Br, 5-Cl 3-chloro-2-pyridinYl H phenyl S 3-Br, 5-Br 3-chloro-2-pyr dinyl H phenyl S 3-CH 3 , 5-CN 3-chloro-2-pyridflyl H pheny 1 S 3-CH 3 , 5-Cl 3-chloro-2-pyridilyl Cl phenyl S 3-Br, 5-Cl 3-chloro-2-pyr.dllyl C1 phenyl S 3-Br, 5-Br 3-chloro-2-pyridllyl Cl phenyl S 3-CH 3 , 5-CN 3-chloro-2-pyr.dllyl C1 phenyl S 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl Br phenyl S 3-Br, 5-Cl 3-chloro-2-pyridflyl Br phenyl S 3-Br, 5-Br 3-chloro-2-pyridflyl Br phenyl S 3-CH 3 , 5-CN 3-chloro-2-pyrid-nyl Br pheny 1 S 3-CH 3 , 5-Cl 3-chloro-2-pyridinfyl

CF

3 pheny 1 S 3-Br, 5-Cl 3-hoo2-yiiy

CF

3 phenyl S 3-Br, 5-Br 3-chloro-2-pyridlflyl

_CF

3 phenyl S 3-CH 3 , 5-CN 3-chloro-2-pyrdlflY1

JCF

3 -222 A compound represented by the formula (1-D): R14a-1 N 3 NH R13a-1 ( 1-D) 1 -NH-NH-C-NR 8

R

9 6 6 "34 wherein NROR 9 , A 34 , (R 4 )n, R13a-1 and Ri1a-1 represent combinations shown in Table 42 to Table 57.

,223 Table 42 NR'R' A 34 (W), RR1a

NH

2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl H

NH

2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H

NH

2 0 .3-Br, 5-Br 3-chloro--pyridinfyl H

NH

2 0 3-CH 3 , 5-CN 3-chloro-2-pyridlflyl H

NH

2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl Cl

NH

2 0 3-Br, 5-Cl 3-chloro-2-pyrEdEi3 l C1

NH

2 0 3-Br, 5-Br 3-chloro-2-pyridinfyl Cl

NH

2 0 3-CH 3 , 5-CN 3-chloro-2-pyridlflyl Cl

NH

2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl Br

NH

2 0 3-Br, 5-Cl 3-chloro-2-pyridflyl Br

NH

2 0 3-Br, 5-Br 3-chloro-2-pyridlfyl Br

NH

2 0 3-CH 3 P 5-CN 3-chloro-2-pyr-dinfyl Br

NH

2 0 3-CH 3 , 5-Cl 3-chloro-2-pyr.dllyl

CF

3

NH

2 0 3-Br, 5-Cl 3-chloro-2-pyridflyl

CF

3

NH

2 0 3-Br, 5-Br 3-chloro-2-pyrdinfyl

CF

3

NH

2 0 3-CH 3 , 5-CN 3-chloro-2-pyridflyl

CF

3

NHCH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyr-dllYl H

NHCH

3 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl H

NHCH

3 0 3-Br, 5-Br 3-chloro-2-pyridinfyl H

NHCH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyrdinfyl H

NHCH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridflyl Cl

NHCH

3 0 3-Br, 5-Cl 3-chloro-2-pyridifyl Cl

NHCH

3 0 3-Br, 5-Br 3-chloro-2-pyridiflyl C1

NHCH

3 0 3-CH 3 , 5-CN 3 -chloro-2-pyrldflyl Cl

NHCH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl Br

NHCH

3 0 3-Br, 5-Cl 3-chloro-2-pyridflyl Br

NHCH

3 0 3-Br, 5-Br 3-chloro-2-pyridflyl Br

NHCH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridflyl Br

NHCH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyrldflyl

CF

3

NHCH

3 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl

CF

3 NHCH3 0 3-Br, 5-Br 3-chloro-2-pyridlflyl

CF

3

NHCH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridilyl

CF

3 '224 Table 43 NRaR 9

A

34 (R) nR 3 aR14

NHCH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridrlYl H

NHCH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl H

NHCH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyr-dllyl H

NHCH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinfyl H

NHCH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdinfyl Cl

NHCH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl Cl

NHCH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridflYl Cl

NHCH

2

CH

3 0 3-CH- 3 , 5-CN 3-chloro-2-pyridlflyl Cl

NHCH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridflyl Br

N~HCH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl Br

NHCH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridlflyl Br

NHCH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridlflyl Br

NHCH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl

CF

3

NHCH

2

CH

3 0 3-Br, 5-Cl 3-chloyo-2-pyridlflyl

CF

3

NHCH

2

CH-

3 0 3-Br, 5-Br 3-chloro-2-pyridinfyl

CF

3

NHCH-

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridflyl

CF

3 NHCH (CHA) 2 0 3-CH 3 , 5-Cl,_ 3-chloro-2-pyridlflyl H NHCH (CH 3 ) 2 0 3-Br, 5-Cl 3-chloro-2-pyr-dinfyl H NHCH (CHA) 2 0 3-Br, 5-Br 3-chloro-2-pyridlflyl H NHCH (CH 3 ) 2 0 3-CH 3 , 5-CN 3-chloro-2-pyrdinfyl H NHCH (CH 3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyr3-dlfyl Cl NHCH (CH 3 ) 2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl C1 N'HCH (CH 3 ) 2 0 3-Br, 5-Br 3-chloro-2-pyridlflyl Cl NHCH (CH 3 ) 2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinfyl C1 NHCH (CH 3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridiflyl Br NHCH (CHD) 2 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl Br NHCH (CHD) 2 0 13-Br, 5-Br 3-chloro-2-pyricinyl Br NHCH (CH 3 ) 2 0 3-CH 3 , 5-CN 3-chloro-2-pyrdinfyl Br NHCH (CH 3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3 NHCH (CH 3 ) 2 0 3-Br, 5-Cl 3-chloro-2-pyridilyl

CF

3 NHCH (CH 3 ) 2 10 3-Br, 5-Br 3-chloro-2-pyridifyl

CF

3 NHCH (CH 3 ) 2 10 3-CH 3 , 5-CN I3-chloro-2-pyridiflyl

CF

3 .225 Table 44

NR

6 R' 4 R4 R 1 3 a-1 R 1 4 a- 1 NHC (CH 3 ) 3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H NHC (CH 3 ) 3 0 3-Br, 5-Cl 3-chloro-2-pyrBdrfyl H

NHC(CH

3

)

3 0 3-Br, 5-Br 3-chloro-2-pyrCdNfyl H NHC (CH 3 ) 3 0 3-CH 3 , 5-CN 3-chloro-2-pyrdinyl H

NHC(CH

3

)

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdifyl Cl

NHC(CH

3

)

3 0 3-Br, 5-Cl 3-chloro-2-pyrBdrnyl Cl NHC (CH 3 ) 3 0 3-Br, 5-Br 3-chloro-2-pyrCdNnyl Cl NHC (CH 3 ) 0 3-CH 3 , 5-CN 3-chloro-2-pyrBdrfyl Cl

NHC(CH

3

)

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl Br NHC (CHO 3 0 3-Br, 5-Cl 3-chloro-2-pyrdinyl Br NHP (CH 3 ) 3 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br

NHC(CH

3

)

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br NHC (CH 3 ) 3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3 NHC (CH 3 ) 3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3 NHC (CHO 3 0 3-Br, 5-Br 3-chloro-2-pyridifyl CF 3

NHC(CHO)

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridiyl CF 3 N (CHO 2 0 3-CH 3 , 5-Cl ,3-chloro-2-pyridinyl H N (CH 3 ) 2 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl H N (CHO) 2 0 3-Br, 5-Br 3 -chloro-2-pyridinyl H N (CHO) 2 0 3-CH 3 , 5-CN 3-chloro-2-pyr.d3nyl H N (CH 3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Cl N (CHO 2 0 3-Br, 5-Cl 3-chloro-2-pyr.d3nyl Cl N (CH 3 ) 2 0 3-Br, 5-Br 3-chloro-2-pyridlinyl Cl Nq (Gil 3 ) 2 0 3-CH- 3 , 5-CN 3-chloro-2-pyridinyl Cl N (CHD) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyr3-diflyl Br N (CH 3 ) 2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br N (CHO) 2 0 3-Br, 5-Br 3-chloro-2-pyridiflyl Br Nq(CH 3 ) 2 0 3-CH 3 , -5-CN 3-chloro-2-pyridinyl Br' Nq(CHO) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl CF 3 N (CH 3 ) 2 0__ 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3 N (CHO) 2 0 3-Br, 5-Br 3 chloro-2-pyridinyl CF 3 N (CH 3 ) 2 0 3-Gil 3 , 5-CN 13-chloro-2-pyridinyl CF 3 226 Table 45

NR

8

R

9 A 34 (R') R13- R 4 N (CH 2

CH

3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlrlyl H N (CH 2

CH

3 ) 2 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl H N (CH 2

CH

3 ) 2 0 13-Br, 5-Br 3-chloro-2-pyrdinfyl H N (CH 2

CH

3 ) 2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H N (CH 2

CH

3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-gyridiflyl Cl N (CH 2

CH

3 ) 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl C1. N (CH 2

CH

3 ) 2 0 3-Br, 5-Br 3-chloro-2-pyridlflyl C1 N (CH 2

CH

3 ) 2 0 3-CH 3 , 5-CN 3-chloro-2-pyridilyl C1 N (CH 2

CH

3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlnyl Br N (CH 2

CH

3 ) 2 0 3-Br, 5-Cl 3-chloro-2-pyrdl-fyl Br N (CH 2

CH

3 ) 2 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br N (CH 2

CH

3 ) 2 0 3-Cl 3 , 5-CN 3-chloro-2-pyridflyl Br N (CH 2

CH

3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridllyl.

CF

3 N (CH 2

CH

3 ) 2 0 3-Br, 5-Cl 3-chloro-2-pyridflYl

CF

3 N (CH 2

CH

3 ) 2 0 3-Br, 5-Br 3-chloro-2-pyrdinfyl

CF

3 N (CH 2

CH

3 ) 2 0 3-CH 3 , 5-CN 3-chloro-2-pyridiflyl

CF

3 N{CH (CH 3 ) 2

)

2 0 3-CH 3 , 5-Cl 3-chloro-2-pyr-d-fyl H N{CH (CH 3 ) 2

)

2 0 3-Br, 5-Cl 3-chloro-2-pyridl-fyl H N{(CH (CH 3 ) 2 1 2 0 3-Br, 5-Br 3-chloro-2-pyridflyl H N{ICH (CH 3 ) 2 1 2 0 3-CH 3 , 5-C;N 3-chloro-2-pyridflyl H N{(CH (CH 3 ) 2)2 0 3-CH 3 , 5-Cl 3-chloro-2-pyr-dlfyl Cl N{(CH (CH 3 ) 2 1 2 0 3-Br, 5-Cl 3-chloro-2-pyrdinryl Cl N{ICH (CH 3 ) 2 1 2 0 3-Br, 5-Br 3-chloro-2-pyridflyl Cl N fCH (CH 3 ) 2 1 2 .0 3-CH 3 , 5-CN 3-chloro-2-pyr2idinyl Cl N{fCH (CH 3 ) 2 1 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridilyl Br N{fCH (CH 3 ) 2 1 2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br N{(CH (CH 3 ) 2

)

2 0 3-Br, 5-Br 3-chloro-2-pyridflyl Br N{fCH (CHD) 2 1 2 0 3-CH 3 , 5-CN 3-chloro-2-pyrdinfyl Br N (CH (CH 3 ) 2 1 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridflyl

CF

3 N {CH (CH 3 ) 2

)

2 0 3-Br, 5-Cl 3-chloro-2-pyridflyl

CF

3 N{fCH (CH 3 ) 2 1 2 0 3-Br, 5-Br 3-chloro-2-pyrid-nyl

CF

3 N{ICH (CH 3 ) 2 12 0 3-CH- 3 , 5-CN 3-chloro-2-pyrdf:

F

,227 Table 46

NR

8

R

9 A34 (R 4 )n R 13 a 1 R a-1 cyclopropylamino 0 3-CH 3 , 5-Cl 3-chloro-2-pyridifYl H cyclopropylanino 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H cyclopropylanino 0 3-Br, 5-Br 3-chloro-2-pyridinyl H cyclopropylano 0 3-CH 3 , 5-CN 3-chloro-2-pyridflYl H cyclopropylamino 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Cl cyclopropylamiflo 0 3-5r, 5-Cl 3-chloro-2-pyridflyl Cl cyclopropylamiflo 0 3-Br, 5-Br 3-chloro-2-pyridifyl Cl cyclopropylamino 0 3-CM 3 , 5-CN 3-chloro-2-pyridlflyl Cl cyclopropylamino 0 3-CM 3 , 5-Cl 3-chloro-2-pyridinfyl Br cyclopropylamino 0 3-Br, 5-Cl 3-chloro-2-pyrCdlyl Br cyclopropylaminfo 0 3-Br, .5-Br 3-chloro-2-pyridinyl Br cyclopropylamino 0 3-CH 3 , 5-CN 3-chloro-2-pyridiflyl Br cyclopropylamiflo 0 3-CM 3 , 5-Cl 3-chloro-2-pyridilyl

CF

3 cyclopropylamino 0 3-Br, 5-Cl 3-chloro-2-pyridflyl

CF

3 cyclopropylamiflo 0 3-Br, 5-Br 3-chloro-2-pyridflYl

CF

3 cyclopropylamiflo 0 3-CM 3 , 5-CN 3-chloro-2-pyr.dllyl

CF

3 cyclobutylamino 0 3-CH 3 , 5-Cl 3-chloro-2-pyr-dinfyl H cyclobutylam.no 0 3-Br, 5-Cl 3-chloro-2-pyr-dilyl H cyclobutylam-no 0 3-Br, 5-Br 3-chloro-2-pyr.dfyl H cyclobutylauino 0 3-CM 3 , 5-CN 3-chloro-2-pyridflyl H cyclobutylamiflo 0 3-CM 3 , 5-Cl 3-chloro-2-pyridlflyl Cl cyclobutylamino 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl Cl cyclobutylamino 0 3-Br, 5-Br 3-chloro-2-pyridiflyl Cl cyclobutylam-no 0 3-CM 3 , 5-CN 3-chloro-2-pyridinfyl Cl cyclobutylamino 0 3-CM 3 , 5-Cl 3-chloro-2-pyr-dllyl Br cyclobutylamino 0 3-Br, 5-Cl 3-chloro-2-pyridilyl Br cyclobutylamino 0 3-Br, 5-Br 3-chloro-2-pyrdinfyl Br cyclobutylamino 0 3-CM 3 , .5-CN 3-chloro-2-pyridlflyl Br cyclobutylamino 0 3-CM 3 , 5-Cl 3-chloro-2-pyrdinfYl

CF

3 cyclobutylau-no 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl

CF

3 cyclobutylamino 0 3-Br, 5-Br 3-chloro-2-pyrdinl c C 3 cyclobutylamino 0 3-CM 3 , 5-CN 3-chloro-2-pyridflyl

CF

3 ,228 Table 47

NRR

9 A 34 (R 4 )n

R

13 R4a-1 cyclopentylamino 0 3-CH 3 , 5-Cl 3-chloro-2-pyridiyl H cyclopentylamino 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H cyclopentylamino 0 3-Br, 5-Br 3-chloro-2-pyridinyl H cyclopentylamino 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H cyclopentylamino 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdinfyl C1 cyclopentylamino 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl cyclopentylamin 0 3-Br, 5-Br 3-chloro-2-pyrdifyl Cl cyclopentylamino 0 3-CH 3 , S-CN 3-chloro-2-pyridinfyl Cl cyclopentylamino 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdi.fyl Br cyclopentylamilo 0 3-Br, 5-Cl 3-chloro-2-pyridinfyl Br cyclopentylamilo 0 3-Br, 5-Br 3-chloro-2-pyridinfyl Br cyclopentylamilo 0 3-CH 3 , 5-CN 3-chloro-2-pyr-dlfyl Br cyclopentylamino 0 3-CH 3 , 5-Cl 3-chloro-2-pyr-dlfyl

CF

3 cyclopentylamino 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl

CF

3 cyclopentylamino 0 3-Br, 5-Br 3-chloro-2-pyr.d3nyl

CF

3 cyclooentylamino 0 3-CH 3 , 5-CN 3-chloro-2-pyridilyl

CF

3 cyclohexylamino 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdinfyl H cyclohexylamilo 0 3-Br, 5-Cl 3-chloro-2-pyr-dinfyl H cyclohexylamino 0 3-Br, 5-Br 3-chloro-2-pyridinfyl H cyclohexylamino 0 3-CH 3 , 5-CN 3-chloro-2-pyr.dllyl H cyclohexylamino 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl Cl cyclohexylamilo 0 3-Br, 5-Cl 3-chloro-2-pyridrlyl C1 cyclohexylamino 0 3-Br, 5-Br 3-chloro-2-pyridflyl Cl cyclohexylam.no 0 3-CH 3 , 5-CN 3-chloro-2-pyridilyl Cl cyclohexylamilo 0 3-CH 3 , 5-Cl 3-chloro-2-pyridiflyl Br cyclohexylamino 0 3-Br, 5-Cl 3-chloro-2-pyridflyl Br cyclohexylamino 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br cyclohexylamino 0 3-CH 3 , 5-CN 3-chloro-2-pyridiflyl Br cyclohexylamino 0 3-CH 3 , 5-Cl 3-chloro-2-pyridilyl

CF

3 cyclohexylamino 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl

CF

3 cyclohexylamino 0 3-Br, 5-Br 3-chloro-2-pyridilyl

CF

3 cyclohexylamino 10 13-CH 3 , 5-CN 13-chloro-2-pyr-dinfyl

CF

3 .229 Table 48

NRR

9

A

34

(R

4 )R Ri 4 a-1 aniline 0 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl H anilino 0 3-Br, 5-Cl 3-chloro-2-pyridflyl H aniline 0 3-Br, 5-Br 3-chloro-2pyridinyl H anilino 0 3-CH 3 , 5-CN 3-chloro-2-pyridflyl H anilino 0 3-OH,, 5-Cl 3-chloro-2-pyrldflyl Cl anilino 0 3-Br, 5-Cl 3-chloro-2-pyridflyl Cl anilino 0 3-Br, 5-Br 3-chloro-2-pyridiyl Cl anilino 0 3-CH 3 , 5-CN 3-chloro-2-pyridflyl Cl anilino 0 3-OH 3 , 5-Cl 3-chloro-2-pyridflyl Br anilino 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br aniline 0 3-Br, 5-Br 3-chloro-2-pyridilyl Br anilino 0 3-OH 3 , 5-CN 3-chloro-2-pyridflyl Br anilino 0 3-CH 3 , 5-Cl 3-chloro-2-pyridilyl

CF

3 anilino 0 3-Br, 5-Cl 3-chloro-2-pyrdinfyl

CF

3 anilino 0 3-Br, 5-Br 3-chloro-2-pyridilyl

CF

3 anilino 0 3-CH 3 , 5-ON 3-chloro-2-pyridilYl

CF

3 pyrrolidin-1-yl 0 3-CH 3 , 5-Cl_ 3-chloro-2-pyridilyl H pyrrolidin-1-yl 0 3-Br, 5-Cl 3-chloro-2-pyridilyl H pyrrolidin-1-yl 0 3-Br, 5-Br 3-chloro-2-pyridilYl H pyrrolidin-1-yl 0 3-CH 3 , 5-CN 3-chloro-2-pyridilyl H pyrrolidin-1-yl 0 3-OH 3 , 5-Cl 3-chloro-2-pyridinyl Cl pyrrolidin-1-yl 0 3-Br, 5-Cl 3-chloro-2-pyridilyl Cl pyrrolidin-1-yl 0 3-Br, 5-Br 3-chloro-2-pyridilyl Cl pyrrolidin-l-y1 0 3-OH 3 , 5-CN 3-chloro-2-pyridilyl Cl pyrrolidin-1-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridilyl Br pyrrolidin-1-yl _2 3-Br, 5-Cl 3-chloro-2-pyridilyl Br pyrrolidin-l-yl 0 3-Br, 5-Br 3-chloro-2-pyridinfyl Br pyrrolidin-1- 1 0 3-CH 3 , 5-O.N 3-chloro-2-pyridilyl Br pyrrolidin-1-yl 0 3-OH 3 , 5-Cl 3-chloro-2-pyridilvl

CF

3 pyrroliciin-1-yl 0 3-Br, 5-Cl 3-chloro-2-pyridilyl

CF

3 pyrrolidin-1-yl 0 3-Br, 5-Br 3-chloro-2-pyridilYl

CF

3 pyrrolidin-1-yl 0 O-3-CH 3 , 5-ON J3-chloro-2-pyridilYl

CF

3 .230 Table 49 NR"R'

A

3 4

(RR

4 ) R_ __14a-1 piperidin-l-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H piperOdin-1-yl 0 3-Br, 5-Cl 3-chloro-2-pyridinYl H piperidOn-1-yl 0 3-Br, 5-Br 3-chloro-2-pyridinyl H pOperadin-1-yl 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H piperOdin-l-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyr-d-nyl CI piperidin-1-yl 0 3-Br, 5-Cl 3-chloro-2-pyridinyl C1 piperldin-1-yl 0 3-Br, 5-Br 3-chloro-2-pyridifyl Cl piperOdin-1-yl 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl piperidin-l-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br pOperldin-l-yl 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br pOperidin-1-yl 0 3-Br, 5-Br 3-chloro-2-pyridinyl Br piperidin-O-yl 0 3-CH3, 5-CN 3-chloro-2-pyridinyl Br pOperldin-l-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridil CF 3 piperidin-1-yl 0 3-Br, 5-Cl 3-chloro-2-pyrdifyl CF 3 piperldin-l-yl 0 3-Br, 5-Br 3-chloro-2-pyridiYl CF 3 piperidin-l-yl 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl CF 3 morpholin-4-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H morpholin-4-yl 0 3-Br, 5-Cl 3-chloro-2-pyridilyl H morphOlin-4-yl 0 3-Br, 5-Br 3-chloro-2-pyridinfl H morpholin-4-yl 0 3-C 3 , 5-CN 3-chloro-2-pyridiYl H morpholin-4-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyrid3.flyl CO morpholOn-4-yl 0 3-Br, 5-Cl 3-chloro-2-pyridil Cl morpholin-4-yl 0 3-Br, 5-Br 3-chloro-2-pyridinyl Cl morpholin-4-yl 0 3-C 3 , 5-CN 3-chloro-2-pyridinyl Cl morpholin-4-yl 0 13-CR, 5-Cl 3-chloro-2-pyridiflyl Br morpholin-4-yl 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br morpholin-4-yl 0 3-Br, 5-Br 3-chloro-2-pyriinyl Br morpholin-4-yl 0 3-CR 3 , 5-CN 3-chloro-2-pyridinyl Br morpholin-4-yl 0 3-C 3 , 5-Cl 3-chloro-2-pyridifyl CF 3 morpholin-4-yl 0 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3 morpholin- 4 -yl 0 3-Br, 5-Br 3-chloro-2-pyridiyl CF 3 morpholin-4-yl 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl CF 3 .231 Table 50

NR

8 R' A 3 4 (R 4 )n R1 3 a1

RIO-

1 thlomorpholinf-4 -yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdinfyl H thlomorpholin-4-yl 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl H thiomorpholin-4-y1 0 3-Br, 5-Br 3-chloro-2-pyridflyl H thiomorpholin-4-yl 0 3-CH 3 , 5-CM 3-chloro-2-pyridflyl H thlomorpholifl-4-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdinfyl Cl thlomorpholin-4-y1 0 3-Br, 5-Cl 3-chloro-2-pyr.dlfll C1 thlomorpholin-4-yl 0 3-Br, 5-Br 3-chloro-2-pyridflyl C1 thlomorpholin-4-yl 0 3-CH 3 , 5-CN 3-chloro-2-pyrdlflI C1 thlornorpholifl-4-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyr.dlyl Br thlomorpholin-4-yl 0 3-Br,- 5-Cl 3-chloro-2-pyrdinfyl Br thlomorpholin-4-yl 0 3-Br, 5-Br 3-chloro-2-pyrdflyl Br thiomorpholin-4-yl_ 0 3-CH 3 , 5-CM 3-chloro-2-pyridflyl Br thlomorpholin-4-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridflyl

CF

3 thiomorpholin-4-yl 0 3-Br, 5-Cl 3-chloro-2-pyridflyl

CF

3 thlomorpholin-4-yl 0 3-Br, 5-Br 3-chloro-2-pyr.dfyl

CF

3 thlomdrpholin-4-yl 0 3-CH 3 , 5-CN 3-chloro-2-pyridflyl

CF

3 l-mrethylpiperazifl-4-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyradflyl H l-methylpiperazil-4-yl 0 3-Br, 5-Cl 3-chloro-2-pyridflyl H l-methylpiperazlrl- 4 -yl 0 3-Br, 5-Br 3-chloro-2-pyridfl 1 H 1-methylpiperazifl-4-yl 0 3-CH 3 , 5-CM 3-chloro-2-pyridilflH l-methylpiperazifl-4-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridflyl Cl l-methylpiperazii-4-yl 0 3-Br, 5-Cl 3-chloro-2-pyridflyl Cl 1-methylplperazinf-4-yl 0 3-Br, 5-Br 3-chloro-2-pyridflyl Cl l-methylpiperazifl-4-yl 0 3-CH 3 r 5-CM 3-chloro-2-pyridflyl Cl l-methylpperazinf-4-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyr-dlyl Br l-methylpiperazin-4-yl 0 3-Br, 5-Cl 3-chloro- 2-pyridflyl Br 1-methylplperazinf-4-yl 0 3-Br, 5-Br- 3-chloro-2-pyrin2fyl Br l-methylpiperazifl-4-yl 0 3-CH 3 , 5-CM 3-chjloro-2-pyridinyl Br l-methylpiperazifl-4-yl 0 3-CH 3 , 5-Cl 3-chloro-2-pyridilyl

CF

3 1-methylpi.peraz3.n-4-yl 0 3-Br, 5-Cl 3-chloro-2-pyridlyl F 1-methylpiperazli- 4 -yl 0 3-Br, 5-Br 3-chloro-2-pyr-dlfyl

CF

3 ] 1-mehylpiprfazn4yl 0 13-CH 3 , 5-CMN 3-chloro-2-pyr.diflyl

CF

3 232 Table 51 NRR A 34

(R

4 3)1

NH

2 s 3-CH 3 , 5-Cl 3-chloro-2-pYrldifyl H

NH

2 s 3-Br, 5-Cl 3-chloro-2-pyrdiryl H

NH

2 S 3-Br, 5-Br 3-chloro-2-pyridflyl H

NH

2 S 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

NH

2 S 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl Cl

NH

2 S 3-Br, 5-Cl 3-chloro-2-pyredinyl Cl

NH

2 S 32-Br, 5-Br 3-chloro-2-pyr dlflyl Cl

NH

2 S 3-CM 3 , 5-CN 3-chloro-2-pyridifyl C1

NH

2 S 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br

NH

2 5 3-Br, 5-Cl 3-chloro-2-pyridinvll Br

NH

2 S 3-Br, 5-Br 3-chloro-2-pyridifyl Br

NH

2 S 3-CM 3 , 5-CN 3-chloro-2-pyridifyl Br

NH

2 S 3-CM 3 , 5-Cl 3-chloro-2-pyridinfl

CF

3

NH

2 S 3-Br, 5-Cl 3-chloro-2-pyrdinfyl

CF

3

NH

2 S 3-Br, 5-Br 3-chloro-2-pyridlflyl

CF

3

NH

2 S 3-CM 3 , 5-CN 3-chloro-2-pyr-dllyl

CF

3

NHCH

3 S 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl H

NHCH

3 S 3-Br, 5-Cl 3-chloro-2-pyr-dinfyl H

NHCH

3 S 3-Br, 5-Br 3-chloro-2-pyridflyl H

NHCH

3 S 3-CM 3 , 5-CN 3-chloro-,2-pyridflyl H

NHCH

3 S 3-CH 3 , 5-Cl 3-chloro-2-pyridflYl Cl

NHCH

3 S 3-Br, 5-Cl 3-chloro-2-pyridflyl Cl NHC14 3 S 3-Br, 5-Br 3-chloro-2-pyrdinfyl Cl

NHCH

3 S 3-CH 3 , 5-CN 3-chloro-2-pyridflyl Cl

NHCH

3 S 3-CH 3 , 5-Cl 3-chloro-2-pyrdinfyl Br

NHCH

3 S 3-Br, 5-Cl 3-chloro-2-pyridflYl Br

NHCH

3 S 3-Br, 5-Br 3-chloro-2-pyridflyl Br

NHCH

3 s 3-CM 3 , 5-CN 3-chloro-2-pyridflyl Br

NHCH

3 S 3-CM 3 , 5-Cl 3-chloro-2-pyridflyl

CF

3

NHCH

3 S 3-Br, 5-Cl 3-chloro-2-pyridflyl

CF

3

NHCH

3 S 3-Br, 5-Br 3-chloro-2-pyrldflYl

CF

3

NHCH

3 S 3-CM 3 , 5-CN 3-chloro-2-pyrldfyl

CF

3 233 Table 52

NR

8 R' A 3 4 (R)-R

NHCH

2 C11 3 S 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl H

NHCH

2

CH

3 S 3-Br, 5-Cl 3-chloro-2-pyridflyl H

NHCH

2

CH

3 S 3-Br, 5-Br 3-chloro-2-pyridinyl H

NHCH

2

CH

3 S 3-CH 3 , 5-CN 3-chloro-2-pyridifyl H

NHCH

2

CH

3 S 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl Cl

NHCH

2

CH

3 S 3-Br, 5-Cl 3-chloro-2-pyridlflyl Cl

NHCH

2

CH

3 s 13-Br, 5-Br 3-chloro-2-pyridflyl Cl

NHCH

2

CH

3 S 3-CH 3 , 5-CN 3-chloro-2-pyridlflyl Cl

NHCH

2

CH

3 S 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl Br

NHCH

2

CH

3 S 3-Br, 5-Cl 3-chloro-2-pyridlflyl Br

NHCH

2

CH

3 s 3-Br, 5-Br 3-chloro-2-pyridiflyl Br

NHCH

2

CH

3 S 3-CH 3 , 5-CN 3 -chloro-2-pyr3.dlfyl Br

NHCH

2

CH

3 S 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl

CF

3

NHCH

2

CH

3 S 3-Br, 5-Cl 3-chloro-2-pyridil_

CF

3

NHCH

2

CH

3 S 3-Br, 5-Br 3-chloro-2-pyrdinfyl

CF

3

NHCH

2

CH

3 S 3-CH 3 , 5-CN 3-chloro-2-pyridinfyl

CF

3

NHCH(CMY)

2 S 3-CH 3 , 5-Cl ,3-chloro-2-pyridiflyl H NHCH (CH 3 ) 2 S 3-Br, 5-Cl 3-chloro-2-pyrdinfyl H NHCH (CH 3 ) 2 S 3-Br, 5-Br 3-chloro-2-pyridifly1 H NHCH (CH 3 ) 2 S 3-CH 3 , 5-CN 3-chloro-2-pyridxflyl H

NHCI-(CH

3 ) S 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl C1 NHCH (CH 3 ) S 3-Br, 5-Cl 3-chloro-2-pyridinfyl Cl NHCH (CH 3 ) 2 S 3-Br, 5-Br 3-chloro-2-pyridiflyl C1 NH-CH (CH- 3 ) 2 S 3-CH- 3 , 5-CN 3-chloro-2-pyridlflyl C1 NHCH (CH 3 ) 2 S 3-CH 3 , 5-Cl 3-chloro-2-pyridiflyl Br NHCH (CH 3 ) 2 S 3-Br, 5-Cl 3-chloro-2-pyridiflyl Br NHCH (CH 3 ) 2 S 3-Br, 5-Br 3-chloro-2-pyridiflyl Br NHCH (CH 3 ) 2 S 3-CH 3 , 5-CN 3-chloro-2-pyrdinfyl Br NHCH (C1 3 ) 2 S 3-CH 3 , 5-Cl 3-chloro-2-pyri~diflyl

CF

3 NHCH (CH 3 ) S 3-Br, 5-Cl 3-chloro-2-pyridiflyl

CF

3 NHCH (CH 3 ) 2 S 3-Br, e-Br 3-chloro-2-pyridiflyl

CF

3 NHCH (CH 3 ) S I3-CH 3 , 5-CN 3-chloro-2-pyridilyl

CF

3 ,234 Table 53

NR

9

R

9 A (R R NHC (CH 3 ) 3 S 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl H NHC (CH 3 .. S 3-Br, 5-Cl 3-chloro-2-pyr-d-iyl H NHC (C 3

).

3 S 3-Br, 5-Br 3-chloro-2-pyr-l-nyl H NSC (CH 3

)

3 S 3-CR 3 , 5-CN 3-chloro-2-pyrdYl H NHC (CH 3 ) 3 S 3-CR 3 , 5-Cl 3-chloro-2-pyridinfyl Cl NHC (CH 3 ) 3 S 3-Br, 5-Cl 3-chloro-2-pyr-dinfyl C1

NHC(CH

3

)

3 S 3-Br, 5-Br 3-chloro-2-pyridinyl Cl NHC (CH 3 ) 3 S 3-CH 3 , 5-CN 3-chloro-2-pyridlflyl C1 NHC (CH 3 ) 3 S 3-CH 3 , 5-Cl 3-chloro-2-pyridflvl Br

NHC(CH

3

)

3 S 3-Br, 5-Cl 3-chloro-2-pyrCdlfYl Br NHC (CH 3 ) 3 S 3-Br, 5-Br 3-chloro-2-pyrldflYl Br NH-C (CH 3 ) 3 S 3-CR 3 , 5-CN 3-chloro-2-pyridflyl Br NHC (CH 3 ) 3 S _3-CR 3 , 5-Cl 3-chloro-2-pyridflyl

CF

3

NHC(CH

3 ) S 3-Br, 5-Cl 3-chloro-2-pyridiyls.

CF

3

NHC(CH

3

)

3 S 3-Br, 5-Br 3-chloro-2-pyridinvy

CF

3 NHC (CH 3 ) 3 S 3-CR 3 , 5-CN 3-chloro-2-pyridflyl

CF

3 N (CH 3 ) 2 S 3-CH 3 , 5-Cl 3-chloro-2-pyridflYl H N (CH 3 ) 2 S 3-Br, 5-Cl 3-chloro-2-pyridflyl H N (CH 3 ) 2 S 3-Br, 5-Br 3-chloro-2-pyr-dllyl H N (CH 3 ) 2 S 3-CH 3 , 5-CN 3-chloro-2-pyridflYl H N (CH 3 ) 2 S 3-CR 3 , 5-Cl 3-chloro-2-pyrdifyl Cl N (CH 3 ) 2 S 3-Br, 5-Cl 3-chloro-2-pyrdil-f _~ Cl N (CH 3 ) 2 S 3-Br, -5-Br 3-chloro-2-pyrdinfyl Cl N (CH 3

)

2 S I 3-C 'H 3 , 5-CN 3-chloro-2-pyridinyl Cl N (CH 3 ) 2 S 3-CH 3 , 5-Cl 3-chloro-2-pyrdinfyl Br N (CH 3 ) 2 S 3-Br, 5-Cl 3-chloro-2-pyr-dllyl Br N (CH 3 ) 2 S 3-Br, 5-Br 3-chloro-2-pyr-cllfyl Br N (CH 3 ) 2 S 3-CH 3 , 5-CM 3-chloro-2-pyrdinfyl Br N (CR 3 ) 2 s 3-CR 3 , 5-Cl 3-chloro-2-pyr-dflyl

CF

3 N (CH 3 ) 2 S 3-Br, 5-Cl 3-chloro-2-pyr.dlyl

CF

3 N (CH 3 ) 2 S- 3-Br, 5-Br 3-chloro-2-pyrdinfyl CF N (CH 3 ) 2 s 3-CR 3 , 5-CM t3-chloro-2-pyrdinfyl

CF

235 Table 54

NR

8

R

9 A 3 4 (R'), R______13a-1__________ R 1 4 al N (CH 2

CH

3 ) 2 S 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl H N (CH 2

CH

3 ) 2 S 3-Br, 5-Cl 3-chloro-2-pyridinfyl H N (CH 2 CHi 3 ) 2 S 3-Br, 5-Br 3-chloro-2-pyridinfyl H N (CH 2

CH

3 ) 2 S 3-CH 3 , 5-CN 3-chloro-2-pyridflyl H N (CH 2

CH

3 ) 2 S 3-CH 3 , 5-Cl 3-chloro-2-pyrldflyl Cl N (CH 2

CH

3 ) 2 S 3-Br, 5-Cl 3-chloro-2-pyridflyl Cl N (CH 2

CH

3 ) 2 S 3-Br, 5-Br 3-chloro-2-pyrdinfyl Cl N (CH 2

CH

3 ) 2 S 3-CH 3 , 5-CN 3-chloro-2-pyrldflYl CL N (CH 2

CH

3 ) 2 S 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br N (CH 2

CH

3 ) 2 S 3-Br, 5-Cl 3-chloro-2-pyrdinfyl Br N (CH 2

CH

3 ) 2 S 3-Br, 5-Br 3-chloro-2-pyridflyl Br N (CH 2

CH

3 ) 2 S 3-CR 3 , 5-CN 3-chloro-2-pyridflyl Br N (CH 2

CH

3 ) 2 S 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl

CF

3 N (CH 2

CH

3 ) 2 5 3-Br, 5-Cl 3-chloro-2-pyrdinfl

CF

3 N (CH 2

CH

3 ) 2 S 3-Br, 5-Br 3-chloro-2-pyrldflYl

CF

3 N (CH 2

CH

3 ) 2 S 3-CH 3 , 5-CN 3-chloro-2-pyrdinfYl

CF

3 cyclopropylamilo S 3-CH 3 , 5-Cl 3-chloro-2-pyr-dinfyl H cyclopropylafllfo S 3-Br, 5-Cl 3-chloro-2-pyrdinfyl H cyclopropylaminfo S 3-Br, 5-Br 3-chloro-2-pyrdinfyl H cyclopropylaminfo S 3-CRi 3 , 5-CN 3-chloro-2-pyr.dlYl H cyclopropylamiflo S 3-CH 3 , 5-Cl 3-chloro-2-pyridflyl Cl cyclopropylamilo S 3-Br, 5-Cl 3-chloro-2-pyr.dinfyl Cl cyclopropylamilo S 3-Br, 5-Br 3-chloro-2-pyridflyl Cl cyclopropylaminfo S 3-CH 3 , 5-CN 3-chloro-2-pyridflyl Cl cycJlopropylaminfo S 3-CR 3 , 5-Cl 3-chloro-2-pyr3.dlfyl Br cyclopropylamiflo S 3-Br, 5-Cl 3-chloro-2-pyr-dinfYl Br cyclopropylaminfo S 3-Br, 5-Br 3-chloro-2-pyr.dllyl Br cyclopropylaruifo S 3-CH 3 , 5-CN :3-chloro-2-pyr.dinfyl Br cyclopropylamflo S 3-CR 3 , 5-Cl 3-chloro-2-pyrdinfyl

CF

3 cyclopropylam-no S 3-Br, 5-Cl 3-chloro-2-pyridi.fl

CF

3 cyclopropylamin.fo S 3-Br, 5-Br 3-chloro-2-pyr.dinfly

CF

3 cyclopropylamilo S 3-CH 3 , 5-CN 3-chloro-2-pyr.dllYl

CF

3 ,236 Table 55 89' A 34 (R 4 ). nR13a-1 Ri10-1 cyclobutylamifo S 3-CH 3 , 5-Cl 3-chloro-2pyridifyl H cyclobutyla~ilo S 3-Br, 5-Cl 3-ch1oro-2-pyridinyl H cyclobutylamifo S 3-Br, 5-Br 3-chloro-2-pyridinyl H cyclobutylamifo S 3-CH 3 , 5-CN 3-chloro-2-pyridlnyl H cyclobutylaino S 3-CH 3 , 5-Cl 3-chloro-2-pyridflyl Cl1 cyclobutylamino S 3-Br, 5-Cl 3-chloro-2-pyridinyl C1 cyclobutylamio S 3-Br, 5-Br 3-chloro-2-pyridinyl Cl cyclobutylamiflo S 3-CH 3 , 5-CN 3-chloro-2-pyridflyl Cl cyclobutylamiflo S 3-CH 3 , 5-Cl 3-chloro-2-pyridflyl Br cyclobutylamifo S 3-Br, 5-Cl 3-chloro-2-pyridifyl Br cyclobutylaino S 3-Br, 5-Br 3-chloro-2-pyridifyl Br cyclobutylamino S 3-CH 3 , 5-CN 3-chloro-2-pyridflyl Br cyclobutylamino S 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl

CF

3 cyclobutylamino S 3-Br, 5-Cl 3-chloro-2-pyridifyl

CF

3 cyclobutylamilo S 3-Br, 5-Br 3-chloro-2-pyrldfYl

CF

3 cyclobutylainU o S 3-CH 3 , 5-CN 3-chloro-2-pyridfYl

CF

3 cyclopentylamino S 3-CH 3 , 5-Cl 3-chloro-2-pyridlfll H cyclopentylanfo S 3-Br, 5-Cl 3-chloro-2-pyridinyl H cyclopentylamino S 3-Br, 5-Br 3-chloro-2-pyridifYl H cyclopentylamino S 3-CH 3 , 5-CN 3-chloro-2-pyridifyl H cyclopentylamino S 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl Cl cyclopentylamifo S 3-Br, 5-Cl 3-chloro-2-pyridifyl Cl cyclopentylamifo S 3-Br, 5-Br 3-chloro-2-pyridinyl Cl cyclopentylamno S 3-CH 3 , 5-CN 3-chloro-2-pyridifyl Cl cyclopentylamnio S 3-CH 3 , 5-Cl 3-chloro-2-pyridifYl Br cyclopentylauno S 3-Br, 5-Cl 3-chloro-2-pyridifyl Br cyclopentylamifo S 3-Br, 5-Br 3-chloro-2-pyridifyl Br cyclopentylamino S 3-CH,, 5-CN 3-chloro-2-pyridifYl Br cyclopentylaTifo S 3-C- 3 , 5-Cl 3-chloro-2-pyridinyl

CF

3 cyclopentylamino S 3-Br, -Cl 3-chloro-2-pyridifYl

CF

3 .cyclopentylaino S 3-Br, 5-Br 3-chloro-2-pyridifyl

CF

3 cyclopentylamino S 3-CH 3 , 5-CN 3-chloro-2-pyridinyl

CF

3 237 Table 56 _ _ _ _ _ A 34 (R') n R4-1 cyclohexylamiflo S 3-CH 3 , 5-Cl 3-chloro-2-pyridflyl H cyclohexylamino S 3-Br, 5-Cl 3-chloro-2-pyridinyl H cyclohexylamio S 3-Br, 5-Br 3 chloro-2-pyridinyl H cyclohexylamifo S 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H cyclohexylamio S 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Cl cyclohexylamifo S 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl cyclohexylamifo S 3-Br, 5-Br 3-chloro-2-pyrBdrnvl Cl cyclohexylamino S 3-CH 3 , 5-CN 3-chloro-2-pyr-dllyl Cl cyclohexylamiflo S 3-CH 3 , 5-Cl 3-chloro-2-pyridflyl Br cyclohexylaminfo S 3-Br, 5-Cl 3-chloro-2-pyrdinfyl Br cyclohexylamino S 3-Br, 5-Br 3-chloro-2-pyridlYl_ Br cyclohexylamilo S 3-CH 3 , 5-CM 3-chloro-2-pyr-dllyl Br cyclohexylamino S 3-CR 3 , 5-Cl 3-chloro-2-pyridflYl

CF

3 cyclohexylamino S 3-Br, 5-Cl 3-chloro-2-pyrBdrYl

CF

3 cyclohexylamino S 3-Br, 5-Br 3-chloro-2-pyridifyl

CF

3 cyclohexylamino S 3-CH 3 , 5-CN 3-chloro-2-pyridinyl

CF

3 anilino S 3-CR 3 ,I 5-Cl 3-chloro-2-pyridlflyl Ii anilino S 3-Br, 5-Cl 3-chloro-2-pyridflvl H anilino S 3-Br, 5-Br 3-chloro-2-pyridflyl H anilino S 3-CR 3 , 5-CM 3-chloro-2-pyridlflyl H anilino S 3-CR 3 , 5-Cl 3-chloro-2-pyridinly Cl anilino S 3-Br, 5-Cl 3-chloro-2-pyridlflyl Cl anilino S 3-Br, 5-Br 3-chloro-2-pyrldflyl Cl aniline S 3-CR 3 , 5-CM 3-chloro-2-pyridiflyl Cl aniline S 3-CR 3 , 5-Cl 3-chloro-2-pyridlflyl Br aniline S 3-Br, 5-Cl 3-chloro-2-pyridinfyl Br anilino S 3-Br, 5-Br 3-chloro-2-pyridiflyl Br anilino S 3-CR 3 , 5-CM 3-chloro-2-pyridiflyl Br aniline S 3-CR 3 , 5-Cl 3-chloro-2-pyridinfyl

CF

3 aniline S 3-Br, 5-Cl 3-chloro-2-pyridiflyl

CF

3 aniline S 3-Br, 5-Br 3-chloro-2-pyr, il F anilino S 3-CH 3 , 5-CM 3-chloro-2-pyridinfll

CF

.2 38 Table 57

NR

8 R' A 34 (R 4 )n R 13 a-1 R 14 a- 1 morpholin-4-yl S 3-CH 3 , 5-Cl 3-chloro-2-pyridflyl H morpholin-4-yl S 3-Br, 5-Cl 3-chloro-2-pyridllyl H morpholin-4-yl S 3-Br, 5-Br 3-chloro-2-pyridinyl H morpholin-4-yl S 3-CH 3 , 5-CM 3-chloro-2-pyrldilyl H morpholin-4-yl S 3-CH 3 , 5-Cl 3-chloro-2-pyridflYl Cl morpholin-4-yl S 3-Br, 5-Cl 3-chloro-2-pyridflyl Cl morpholin-4-yl S 3-Br, 5-Br 3-chloro-2-pyridflyl C1 morpholin-4-yl S 3-CH 3 , 5-CN 3-chloro-2-pyrdinfyl C1 morpholin-4-yl S 3-CH 3 , 5-Cl 3-chloro-2-pyridilyl Br morpholin-4-y. S 3-Br, 5-Cl 3-chloro-2-pyridflyl Br morpholin-4-yl S 3-Br, 5-Br 3-chloro-2-pyridflyl Br morpholin-4-yl S 3-CH 3 , 5-CN 3-chloro-2-pyridilyl Br morpholin-4-yl S 3-CH 3 , 5-Cl 3-chloro-2-pyr3idinyl CF 3 morpholin-4-yl S 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3 morpholin-4-yl_ S 3-Br, 5-Br 3-chloro-2-pyridflyl

CF

3 morpholin-4-yl S 3-CH 3 , 5-CN 3-chloro-2-pyridinyl

CF

3 239 A compound represented by the formula (1-E): R 14a-1 N 4 3 NH 13a-1 ( -E)

(R

4 2 6 I-NH-NH-S 2

R

0 wherein R1 0 , (R 4 ) n, R 13a- and Ria-i represent combinations shown in Table 58 to Table 60.

-240 Table 58

R

10 (R') R1 3 a-1 R a CH3 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

CH

3 3-Br, 5-Cl 3-chloro-2-pyridinyl H

CH

3 3-Br, 5-Br 3-chloro-2-pyridinyl H

CH

3 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CH

3 3-CH3, 5-Cl 3-chloro-2-pyridinyl Cl

CH

3 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl CH3 3-Br, 5-Br 3-chloro-2-pyridinyl Cl

CH

3 3-CH 3 , 5-CN 3-chloro-2-pyridinyl C1 CH3 3-CH3, 5-Cl 3-chloro-2-pyridinyl Br

CH

3 3-Br, 5-Cl 3-chloro-2-pyridinyl Br

CH

3 3-Br, 5-Br 3-chloro-2-pyridinyl Br

CH

3 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br

CH

3 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl

CF

3

CH

3 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3 CH3 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3

CH

3 3-CH 3 , 5-CN 3-chloro-2-pyridinyl CF 3

CH

2

CH

3 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

CH

2

CH

3 3-Br, 5-Cl 3-chloro-2-pyridinyl H

CH

2

CH

3 3-Br, 5-Br 3-chloro-2-pyridinyl H

CH

2

CH

3 3-CH3, 5-CN 3-chloro-2-pyridinyl H

CH

2

CH

3 3-CH3, 5-Cl 3-chloro-2-pyridinyl Cl CH2CH3 3-Br, 5-Cl 3-chloro-2-pyridinyl C1

CH

2

CH

3 3-Br, 5-Br 3-chloro-2-pyridinyl Cl

CH

2

CH

3 3-CH3, 5-CN 3-chloro-2-pyridinyl Cl CH2CH3 3-CH3, 5-Cl 3-chloro-2-pyridinyl Br

CH

2

CH

3 3-Br, 5-Cl 3-chloro-2-pyridinyl Br CH2CH3 3-Br, 5-Br 3-chloro-2-pyridinyl Br CH2CH3 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br

CH

2

CH

3 3-CH3, 5-Cl 3-chloro-2-pyridinyl CF 3 CH2CH3 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3 CH2CH3 3-Br, 5-Br 3-chloro-2-pyridinyl CF 3 CH2CH3 3-CH3, 5-CN 3-chloro-2-pyridinyl CF 3 ,241 Table 59 Rio (RR) 1 3 a-I

R

4 al

CF

3 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

CF

3 3-Br, 5-Cl 3-chloro-2-pyridinyl H

CF

3 3-Br, 5-Br 3-chloro-2-pyridinyl H

CF

3 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CF

3 3-CH 3 , 5-C,1 3-chloro-2-pyridinyl Cl

CF

3 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl

CF

3 3-Br, 5-Br 3-chloro-2-pyridinyl Cl

CF

3 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl

CF

3 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br

CF

3 3-Br, 5-C1 3-chloro-2-pyridinyl Br

CF

3 3-Br, 5-Br 3-chloro-2-pyridinyl Br

CF

3 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br

CF

3 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl

CF

3

CF

3 3-Br, 5-Cl 3-chloro-2-pyridinyl

CF

3

CF

3 3-Br, 5-Br 3-chloro-2-pyridinyl

CF

3

CF

3 3-CH 3 , 5-CN 3-chloro-2-pyridinyl

CF

3 phenyl 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H phenyl 3-Br, 5-Cl 3-chloro-2-pyridnyyl H phenyl 3-Br, 5-Br 3-chloro-2-pyridinyl H phenyl 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H phenyl 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Cl phenyl 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl phenyl 3-Br, 5-Br 3-chloro-2-pyridinyl Cl phenyl 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl phenyl 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br phenyl 3-Br, 5-Cl 3-chloro-2-pyridinyl Br phenyl 3-Br, 5-Br 3-chloro-2-pyridinyl Br phenyl 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br phenyl 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl

CF

3 phenyl 3-Br, 5-Cl 3-chloro-2-pyridinyl CF 3 phenyl 3-Br, 5-Br 3-chloro-2-pyridinyl

CF

3 phenyl 3-CH 3 , 5-CN 3-chloro-2-pyridinyl

CF

3 242 Table 60 R10

(R

4 )

R

1 3 a~ 1 R14a-1 4-methylphenyl 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H 4-methylphenyl 3-Br, 5-Cl 3-chloro-2-pyridinyl H 4-methylphenyl 3-Br, 5-Br 3-chloro-2-pyridinyl H 4-methylphenyl 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H 4-methylphenyl 3-CH 3 , 5-Cl 3-chloro-2-pyrdifyl Cl 4-methylphenyl 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl 4-methylphenyl 3-Br, 5-Br 3-chloro-2-pyridinyl Cl 4-methylphenyl 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl 4-methylphenyl 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br 4-methylphenyl 3-Br, 5-Cl 3-chloro-2-pyridfinyl Br 4-methylphenyl 3-Br, 5-Br 3-chloro-2-pyridinyl Br 4-methylphenyl 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br 4-methylphenyl 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl

CF

3 4-methylphenyl 3-Br, 5-Cl 3-chloro-2-pyridinyl

CF

3 4-methylphenyl 3-Br, 5-Br 3-chloro-2-pyridfinyl

CF

3 4-methylphenyl 3-CH 3 , 5-CN 3-chloro-2-pyridinyl

CF

3 - 243 A compound represented by the formula (1-F): R14a-1 ~ I~N 3 R 13a-1 I (R4),F 12 (12F 6 1 H--NH-SO2NR"R1 wherein NR"1 12 (R') R13a-1 and R 14a- represent combinations shown in Table 61.

244 Table 61 NRuR 1 2

(R

4 ),, R 3 a-1 Ru1-1

N(CH

3

)

2 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

N(CH

3

)

2 3-Br, 5-Cl 3-chloro-2-pyridinyl H N (CH 3 ) 2 3-Br, 5-Br 3-chloro-2-pyr idinyl_ H N (CH 3 ) 2 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H N (CH 3

)

2 3-CH 3 , 5-Cl 3-chloro-2-pyrdifyl C1 N (CH 3 ) 2 3-Br, 5-Cl 3-chloro-2-pyridifyl Cl

N(CH

3

)

2 3-Br, 5-Br 3-chloro-2-pyridinyl Cl

N(CH

3

)

2 3-CH 3 , 5-CN 3-chloro-2-pyridinyl C1

N(CH

3

)

2 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br N (CH 3 ) 2 3-Br, 5-Cl 3-chloro-2-pyridinyl Br

N(CH

3

)

2 3-Br, 5-Br 3-chloro-2-pyridinyl_ Br

N(CH

3

)

2 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br

N(CH

3

)

2 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl

CF

3 N (CH 3

)

2 3-Br, 5-Cl 3-chloro-2-pyridinyl

CF

3

N(CH

3

)

2 3-Br, 5-Br 3-chloro-2-pyridinyl

CF

3 N (CH 3 )2 3-CH 3 , 5-CN 3-chloro-2-pyridinyl

CF

3 anilino 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H anilino 3-Br, 5-Cl 3-chloro-2-pyridinyl H anilino 3-Br, 5-Br 3-chloro-2-pyridinyl H anilino 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H anilino 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Cl anilino 3-Br, 5-Cl 3-chloro-2-pyridinyl Cl anilino 3-Br, 5-Br 3-chloro-2-pyridinyl Cl anilino 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Cl anilino 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl Br anilino 3-Br, 5-Cl 3-chloro-2-pyridinyl Br anilino 3-Br, 5-Br 3-chloro-2-pyridinyl Br anilino 3-CH 3 , 5-CN 3-chloro-2-pyridinyl Br anilino 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl

CF

3 anilino 3-Br, 5-Cl 3-chloro-2-pyridinyl

CF

3 anilino 3-Br, 5-Br 3-chloro-2-pyridinyl

CF

3 anilino 3-CH 3 , 5-CN 3-chloro-2-pyridinyl

CF

3 245 A compound represented by the formula (1-G):

(R

14 8)p 3R 3 a- 2 ( 1-G)

(R

4 )r - 2 k -NH-NH-r' 6 31 wherein R 5 , A 31 , (R 4 )n, R 13 a- 2 and (R1 4 a)p represent combinations shown in Table 62.

.246 Table 62

R

5

A

3 1 (R') R 13 8 2

(R

1 4 ) H 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdifyl H H 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H H 0 3-Br, 5-Br 3-chloro-2-pyridinyl H H 0 3-CH 3 , 5-CN 3-chloro-2-pyridifyl H H 0 3-CE 3 , 5-Cl 3-chloro-2-pyrdinfyl 4-Cl H 0 3-Br, 5-Cl 3-chloro-2-pyridifyl 4-Cl H 0 3-Br, 5-Br 3-chloro-2-pyridinyl 4-Cl H 0 3-CE 3 , 5-CN 3-chloro-2-pyridinfyl 4-Cl H 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinfyl 4-Br H 0 3-Br, 5-Cl 3-chloro-2-pyrldlflyl 4-Br H 0 3-Br, 5-Br 3-chloro-2-pyridflyl 4-Br H 0 3-CE 3 , 5-CN 3-chloro-2-pyridflyl 4-Br H 0 3-CE 3 , 5-Cl 3-chloro-2-pyridflyl 4-CF 3 H 0 3-Br, 5-Cl 3-chloro-2-pyridinfyl 4-CF 3 H 0 3-Br, 5-Br 3-chloro-2-pyridilyl 4-CF 3 H 0 3-CE 3 , 5-CN 3-chloro-2-pyridflyl 4-CF 3

CE

3 0 3-CE 3 , 5-Cl 3-chloro-2-pyridflyl H

CE

3 0 3-Br, 5-Cl 3-chloro-2-pyridflyl H

CE

3 0 3-Br, 5-Br 3-chloro-2-pyrid-nyl H

CH

3 0 3-CE 3 , 5-CN 3-chloro-2-pyrdinfyl H

CH

3 .0 3-CE 3 , 5-Cl 3-chloro-2-pyr.idflyl 4-Cl

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyrdinfyl 4-Cl

CE

3 0 3-Br, 5-Br 3-chloro-2-pyr.dllyl 4-Cl

CE

3 0 3-CE 3 , 5-CN 3-chloro-2-pyridflyl 4-Cl

CE

3 0 3-CE 3 , 5-Cl 3-chloro-2-pyridinyl 4-Br

CH-

3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl 4-Br

CE

3 0 3-Br, 5-Br 3-chloro-2-pyrid3.nyl 4-Br

CE

3 .0 3-CE 3 , 5-CN 3-chloro-2-pyridinyl 4-Br

CE

3 0 3-CE 3 , 5-Cl 3-chloro-2-pyridiflyl 4-CF 3

CE

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl 4-CF 3

CE

3 0 3-Br, 5-Br 3-chloro-2-pyrdinfyl 4-CF 3

CE

3 0 3-CE 3 , 5-CN 3-chloro-2-pyridinyl ,4-CF 3 247 A compound represented by the formula (1-H): 14a (R ) 2 N 3 H R13a-2 R H -R(1-H) (R )--- INH-N R 66 32 wherein R 6 , A 32 , (R 4 )n, Ri 3 a- 2 and (R 14 ")p represent combinations shown in Table 63 to Table 74. 5 Table 63

R

6

A

32 (R1) R1 3 a- 2 (R1 4 a)

CH

3 0 3-CH 3 3-chloro-2-pyridinyl H

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

CH

3 0 3-CH 3 , 5-Br 3-chloro-2-pyridinyl H

CH

3 0 3-CH 3 , 5-I 3-chloro-2-pyridinyl H

CH

3 0 3-CH 3 , 5-CH 3 3-chloro-2-pyridinyl H

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CH

3 0 3-Cl 3-chloro-2-pyridinyl H

CH

3 0 3-Cl, 5-Cl 3-chloro-2-pyridinyl H

CH

3 0 3-Cl, 5-Br 3-chloro-2-pyridinyl H

CH

3 0 3-C1, 5-I 3-chloro-2-pyridinyl H

CH

3 0 3-Cl, 5-CH 3 3-chloro-2-pyrid3.nyl H

CH

3 0 3-Cl, 5-CN 3-chloro-2-pyridinyl H

CH

3 0 3-Br 3-chloro-2-pyridinyl H

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl H

CH

3 0 3-Br, 5-I 3-chloro-2-pyrid3.nyl H

CH

3 0 3-Br, 5-CH 3 3-chloro-2-pyridinyl H

CH

3 0 3-Br, 5-CN 3-chloro-2-pyridinyl H

CH

3 0 3-I 3-chloro-2-pyridinyl H

CH

3 0 3-I, 5-Cl 3-chloro-2-pyridinyl H

CH

3 0 3-I, 5-Br 3-chloro-2-pyridinyl H

CH

3 0 3-I, 5-I 3-chloro-2-pyridinyl H

CH

3 0 3-I, 5-CH 3 3-chloro-2-pyridinyl H

CH

3 0 3-I, 5-CN 3-chloro-2-pyridinyl

H

248 Table 64 R______ A 32 (R') ~ R 1 3 a- 2 R 1 4a

CH

3 0 3-CH 3 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl 4-Cl CH3 10 3-CH 3 , 5-Br 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-CH 3 , 5-I 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-CH 3 , 5-,CH 3 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-Cl 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-Cl, 5-Cl 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-Cl, 5-Br 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-Cl, 5-1 3-chloro-2-pyridinyl 4-Cl

CH

3 0 3-C1, 5-CH 3 3-chloro-2-pyridiyl 4-Cl

CH

3 0 3-Cl, 5-CM 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-Br 3-chloro-2-pyrdfyl 4-Cl

CH

3 0 3-Br, 5-Cl i-chloro-2-pyridiyl 4-Cl

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-Br, 5-1 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-Br, 5-CH 3 3-chloro-2-pyrdifyl 4-Cl

CH

3 0 3-Br, 5-CN 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-1 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-1, 5-Cl 3-chloro-2-pyr.dnyl 4-Cl

CH

3 0 3-I, 5-Br 3-chloro-2-pyrid.lyl 4-Cl

CH

3 0 3-I, 5-I 3-chloro-2-pyridifyl 4-C1

CH

3 0 3-, 5-CH 3 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-I, 5-CN 3-chloro-2-pyridinyl 4-Cl 249 Table 65

R

6

A

32

(R

4 )

R

13 a 2 (R1 4 a)

CH

3 0 3-CH 2

CH

3 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3_CH(CH 3

)

2 3-chloro-2-pyridifyl 4-Cl

CH

3 10 -C(CH 3

)

3 3-chloro-2-pyrdifyl 4-Cl

CE

3 0 3-CF 3 3-chloro-2-pyridifyl 4-Cl

CH

3 0 1-OCH 3 3-choro-2-PYridifYl 4-Cl

CH

3 0 3-phenyl 3-chloro-2-pyr~difyl 4-Cl

CH

3 O 3-CH 2

CE

3 , 5-Cl 3-chloro-2-pyridifyl 4-Cl C 3 0 3-CH(CH 3

)

2 , 5-Cl 3-chloro-2-pyrdinyl 4-Cl

C

3 0 3-C(CH 3

)

3 , 5-Cl 3-chloro-2-pyrldifyl 4-Cl

CH

3 0 3-CF 3 , 5-Cl 3-chloro-2-pyridinyl 4-Cl

CH

3 0 3-0CH 3 , 5-Cl 3-chloro-2-pyridifyl 4-Cl

CE

3 10 13-phenyl, 5-Cl 3-chloro-2-pyridflyl 4-Cl

CH

3 0 3-CH 3 , 4-Cl 3-chloro-2-pyridinyl 4-Cl

CH

3 0 3-Cl, 4-Cl 3-chloro-2-pyridifyl 4-Cl

CEH

3 0 3-CH 3 , 6-Cl 3-chloro-2-pyr3-dinfyl 4-Cl

CH

3 0 3-Cl, 6-Cl 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-CE 3 , 4-Cl, 5-Cl 3-chloro-2-pyridifyl 4-Cl

CE

3 0 3-Cl, 4-Cl, 5-Cl 3-chloro-2-pyrdinfl 4-Cl

CH

3 0 3-CH 3 , 5-Cl, 6-Cl 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-Cl, 5-Cl, 6-Cl 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-CE 3 , 5-F 3-chloro-2-pyridinyl 4-Cl

CE

3 10 13-_Cl, 5-F 3-chloro-2-pyridinfyl 4-Cl

CE

3 0 43Br, 5-F 3-chloro-2-pyridiyl 4-Cl C 3 0 3-1, 5-F 3-chloro-2-pyridifyl 4-Cl C 3 10 -Me,4,5-CH=CH-CH=C

-

3-chloro-2-pyr 3d l lyl 4-C l

CH

3 0 3-Cl,4,5-CHCH-CHCH 3-chloro-2-pyrdifyl 4-Cl

CH

3 0 3-Br,4,5-CHCH-CHCH 3-chloro-2-pyridifyl 4-Cl

CH

3 0 3-I,4,5-CECE-CECH- 3-chloro-2-pyridinyl 4-Cl 250 Table 66 R6 A 3 2

(R

4 ). R 132 (R1 4 a)

CH

3 0. 3-CH 3 3-chloro-2-pyridifyl 4-Br

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdinyl 4-Br

CH

3 0 3-CH 3 , 5-Br 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-CH 3 , 5-I 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-CH 3 , 5-CH 3 3-chloro-2-pyrdinyl 4-Br

CH

3 0 3-OH 3 , 5-ON 3-chloro-2-pyridifyl 4-Br

CH

3 0 3-Cl 3-chloro-2-pyridifyl 4-Br

CH

3 0 3-Cl, 5-Cl 3-chloro-2-pyridifyl 4-Br

CH

3 0 3-Cl, 5-Br 3-chloro-2-pyridifyl 4-Br

CH

3 0 3-Cl, 5-I 3-chloro-2-pyridifyl 4-Br

CH

3 0 3-Cl, 5-CH 3 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-41, 5-CN 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-Br 3-chloro-2-pyridinyl 4-Br

OH

3 0 3-Br, 5-Cl 3-chloro-2-pyridiyl 4-Br

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridilyl 4-Br

CH

3 03-chloro-2-pyridinyl 4-Br 0 3-Br, 5--Br

CH

3 0 3-Br, 5-ON 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-Br 3-chloro-2-pyr5dCnyl 4-Br

CH

3 0 3-I 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-I, 5-Cl 3-chloro-2-pyridinyl 4-Br CH3 0 3-,5B -hoo2prdnl 4-Br

CH

3 0 3-I, 5-I 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-I, 5-CM 3 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-I, 5-CN 3-chloro-2-pyridinyl 4-Br 251 Table 67

R

6

A

3 2 (R'). R2 3 a 2 (R_14a

CH

3 0 3-CH 2

CH

3 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-CH(CH 3

)

2 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-C(CH 3

)

3 3-chloro-2-pyridifyl 4-Br

CH

3 0 3-CF 3 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-0CH 3 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-phenyl 3-chloro-2-gyridinyl 4-Br

CH

3 0 3-CH 2

CH

3 F 5-Cl 3-chloro-2-pyridifyl 4-Br

CH

3 0 3-CH~(CH 3

)

2 5-Cl 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-C(CH 3

)

3 , 5-Cl 3-chloro-2-pyridifyl 4-Br

CH

3 0 3-CF 3 , 5-Cl 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-0CH 3 , 5-Cl 3-chloro-2-pyridifyl 4-Br

CM

3 10 3-_phenyl, 5-Cl 3-chloro-2-pyriclinyl 4-Br

CH

3 10 .3-_CH 3 , 4-Cl 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-Cl, 4-Cl 3-chloro-2-pyridinyl 4-Br

CH

3 0 3-CH 3 , 6-Cl 3-chloro-2-pyridinyl 4-Br

CH

3 0' 3-Cl, 6-Cl 3-chloro-2-pyridifyl 4-Br

CH

3 0 3-CM 3 , 4-Cl, 5-Cl 3-chloro-2-pyridinyl 4-Br

CH

3 0 13-C, 4-Cl, 5-Cl 3-chloro-2-pyridinyl 4-Br

CH

3 10 13-_CM 3 , 5-Cl, 6-Cl 3-chloro-2-pyridiflyl 4-Br

CH

3 0 3-Cl, 5-Cl, 6-Cl 3-chloro-2-pyrdinyl 4-Br

CH-

3 10 13- CM 3 , 5-F 3-chloro-2-pyridlflyl 4-Br

CH

3 0 43-Cl, 5-F 3-chloro-2-pyridifyl 4-Br

CH

3 0 3-Br, 5-F 3-chloro-2-pyridifyl 4-Br

CH

3 0 34I, 5-F 3-chloro-2-pyridinyl 4-Br

CH

3 10 3-Me,4,5-CH=CH-CH=CH- 3-chloro-2-pyridinyl 4-Br

CM

3 10 3-Cl,4,5-CH=C-C-ICH- 3-chloro-2-pyridilyl 4-Br

CH

3 0 3-Br,4,5-CHCH-CHC- 3-chloro-2-pyridifyl 4-Br

CH

3 0 3-I,4,5-CM=C-CMCH- 3-chloro-2-pyridinyl 4-Br .252 Table 68

R

6

A

3 2 (R') ~ R 1 3 a- 2 Ra)

CH

3 0 3-CH 3 3-chloro-2-pyridinyl 4-CF 3

CH

3 0 3-CH 3

-

5-C- 3-chloro-2-pyridifyl 4-CF 3

CH

3 0 3-CM 3 , 5-Br 3-chloro-2-pyrd- l 4-CF 3

CH

3 0 3-CH 3 , 5-1 3-chloro-2-pyridinyl 4-CF 3

CM

3 0 3-CH 3 , 5-CM 3 3-chloro-2-pyrldlflyl 4-CF 3

CM

3 0 3-CM 3 , 5-CN 3-chloro-2-pyridlflyl 4-CF 3

CH

3 0 3-C 3-chloro-2-pyr-d-- yl -4-CF 3

CH

3 0 3-Cl, 5-Cl 3-chloro-2-pyr3.dllyl 4-CF 3

CH

3 0 3-Cl, 5-Br 3-chloro-2-pyridlflyl 4-CF 3

CH

3 0 3-Cl, 5-I 3-chloro-2-pyridflyl 4-CF 3

CM

3 -0 3-C1, 5-CM 3 3-chloro-2-pyridlflyl 4-CF 3

CM

3 0 3-Cl, 5-CN 3-chloro-2-pyridlflyl 4-CF 3

CH

3 0 3-Br 3 4-CF 3

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinvl 4-CF 3

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl 4-CF 3

CH

3 10 3-Br, 5- 3-chloro-2-pyridifyl 4-CF 3

CH

3 0 3-Br, 5-CH 3 loro-2-pyridifyl 4-CF 3

CH

3 0 3-Br, 5-CN 3-chloro-2-pyridifyl 4-CF 3

CH

3 0 3-I 3-chloro-2-pyridifyl 4-CF 3

CM

3 0 3-I, 5-Cl 3-chloro-2-pyridlflyl 4-CF 3

CH

3 0 3-I, 5-Br 3-chloro-2-pyr.dinfyl 4-CF 3

CH

3 0 3-I, 5-I 3-chloro-2-pyridiflyl 4-CF 3

CH

3 0 3-1, 5-CM 3 3-chloro-2-pyrid-nyl 4-CF 3

CH

3 0 3-I, 5-CN 3-chloro-2-pyridinyl 4-CF 3 .253 Table 69 R* A32 (R 4 ) ROM (R a)

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridifyl 4-F

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl 4-F

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridifyl 4-F

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridflyl 4-F

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyrldlflyl 4-1

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl 4-1

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl 4-I

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl 4-1

CH

3 0 3-Cl 3 , 5-Cl 3-chloro-2-pyridinyl 4-CH 3

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridifyl 4-CH 3

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridlflyl 4 -CF! 3

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridifyl 4-CF! 3

CH

3 0 3-Cl 3 , 5-Cl 3-chloro-2-pyridifyl 5-Cl

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridifyl 5-Cl

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridifyl 5-Cl

CH

3 0 3-Cl 3 , 5-CN 3-chloro-2-pyr-d3.fyl 5-Cl

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridrlyl 5-Br

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridifyl 5-Br

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridifyl 5-Br

CH

3 0 3-Cl 3 , 5-CN 3-chloro-2-pyridinyl 5-Br

CH

3 0 3-CH 3 1 5-Cl 3-chloro-2-pyr3-dlfyl 5-CF 3 Cl 3 0 3-Br, 5-Cl 3-chloro-2-pyridflyl 5-CF 3

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridikyl 5-CF 3

CH

3 0 3-Cl 3 , 5-CN 3-chloro-2-pyridifyl 5-CF 3

CH

3 0 3-Cl 3 , 5-Cl 3-chloro-2-pyridinyl 4,5-Cl 2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinfyl 4 ,5-Cl 2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridifyl 4,5-Cl 2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridrlyl 4,5-Cl 2

CH

3 0 3-Cl 3 , 5-Cl 3-chloro-2-pyridinyl 4,5-Br 2

CF!

3 0 3-Br, 5-Cl 3-chloro-2-pyridinfyl .4,5-Br 2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridflyl 4,5-Br 2

CH

3 .0 3-Cl 3 , 5-CN 3-chloro-2-pyridlflyl 14,5-Br 2 254 Table 70 R 6 A 3 2 R1 3 a- 2 (R___14a __

CH

3 0 3-CH 3 , 5-Cl 3-fluoro-2-pyrdinyl H

CH

3 0 3-Br, 5-Cl 3-fluoro-2-pyridinyl H

CH

3 0 3-Br, 5-Br 3-fluoro-2-pyridlnyl H

CH

3 0 3-CH 3 , 5-CN 3-fluoro-2-pyridinyl h

CH

3 0 3-CH 3 , 5-f1 3-fluoro-2-pyridinyl 4-Cl

CH

3 0 3-Br, 5-Cl 3-fluoro-2-pyridinyl 4-Cl

CM

3 0 3-Br, 5-Br 3-fluoro-2-pyridinyl 4-Cl

CM

3 0 3-CH 3 , 5-CN 3-fluoro-2-pyridinyl 4-C.

CH

3 0 3-CH 3 , 5-Cl 3-fluoro-2-pyridiryl 4-Br

CH

3 0 3-Br, 5-Cl 3-fluoro-2-pyridinyl 4-Br

CH

3 0 3-Br, 5-Br 3-fluoro-2-pyridiriyl 4-Br

CM

3 0 3-CH 3 , 5-CN 3-fluoro-2-pyridinyl 4-Br

CH

3 0 3-CH 3 , 5-Cl 3-fluoro-2-pyridinyl 4-CF 3

CM

3 0 3-Br, 5-Cl 3-fluoro-2-pyridinyl 4-CF 3

CH

3 0 3-Br, 5-Br 3-fluoro-2-pyridinyl 4-CF 3

CM

3 0 3-CH 3 , 5-CN 3-fluoro-2-pyridinyl 4-CF 3

CH

3 0 3-CM 3 , 5-Cl 3-bromo-2-pyridinyl H

CH

3 0 3-Br, 5-Cl 3-bromo-2-pyridinyl M

CH

3 0 3-Br, 5-Br 3-bromo-2-pyridinyl H

CH

3 0 3-CM 3 , 5-CN 3-bromo-2-pyridinyl H

CH

3 0 3-CM 3 , 5-Cl 3-bromo-2-pyridinyl 4-Cl

CH

3 0 3-Br, 5-Cl 3-bromo-2-pyridinyl 4-Cl

CH

3 0 3-Br, 5-Br 3-bromo-2-pyridinyl 4-Cl

CM

3 0 3-CM 3 , 5-CN 3-bromo-2-pyridinyl 4-Cl

CH

3 0 3-CH3, 5-Cl 3-bromo-2-pyridinyl 4-Br

CH

3 0 3-Br, 5-Cl 3-bromo-2-pyridinyl 4-Br

CH

3 0 3-Br, 5-Br 3-bromo-2-pyridinyl 4-Br

CH

3 0 3-CM 3 , 5-CN 3-bromo-2-pyridinyl 4-Br

CM

3 0 3-CM 3 , 5-Cl 3-bromo-2-pyridinyl 4-CF 3

CH

3 0 3-Br, 5-Cl 3-bromo-2-pyridinyl 4-CF 3

CH

3 0 3-Br, 5-Br 3-bromo-2-pyridinyl 4-CF 3 0 3-CH 3 , 5-CN 3-bromo-2-pyridinyl 4-CF 3 255 Table 71

R

6 A3 (R 4 )n R1 3 a- 2 (R14)

CH

3 0 3-CH 3 , 5-Cl 3-methyl-2-pyridinyl H

CH

3 0 3-Br, 5-Cl 3-methyl-2-pyridinyl H

CH

3 0 3-Br, 5-Br 3-methyl-2-pyridinyl H

CH

3 0 3-CH,, 5-CN 3-methyl-2-pyridinyl H

CH

3 0 3-CH 3 , 5-Cl 3-methyl-2-pyridinyl 4-Cl

CH

3 0 3-Br, 5-Cl 3-methyl-2-pyridinyl 4-Cl

CH

3 0 3-Br, 5-Br 3-methyl-2-pyridinyl 4-Cl

CH

3 0 3-CH 3 , 5-CN 3-methyl-2-pyridinyl 4-Cl

CH

3 0 3-CH 3 , 5-Cl 3-methyl-2-pyrdinyl 4-Br

CH

3 0 3-Br, 5-Cl 3-methyl-2-pyridinyl 4-Br

CH

3 0 3-Br, 5-Br 3-methyl-2-pyridinyl 4-Br

CH

3 0 3-CH 3 , 5-CN 3-methyl-2-pyridinyl 4-Br

CH

3 0 3-CH 3 , 5-Cl 3-methyl-2-pyridinyl 4-CF 3

CH

3 0 3-Br, 5-Cl 3-methyl-2-pyridinyl 4-CF 3

CH

3 0 3-Br, 5-Br 3-methyl-2-pyridinyl 4-CF 3

CH

3 0 3-CH 3 , 5-CN 3-methyl-2-pyridinyl 4-CF 3

CH

3 0 3-CH 3 , 5-Cl 3-trifluoromethyl-2-pyridifYl H

CH

3 0 3-Br, 5-Cl 3-trifluoromethyl-2-pyridinyl H

CH

3 0 3-Br, 5-Br 3-trifluoromethyl-2-pyridifyl H

CH

3 0 3-CH 3 , 5-CN 3-trifluoromethyl-2-pyridinyl H

CH

3 0 2-CH 3 , 5-Cl 3-trifluoromethyl-2-pyridinyl 4-Cl

CH

3 0 3-Br, 5-Cl 3-trifluoromethyl-2-pyridinyl 4-Cl

CH

3 0 3-Br, 5-Br 3-trifluoromethyl-2-pyridinyl 4-Cl

CH

3 0 3-CH 3 , 5-CN 3-trifluoromethyl-2-pyridifyl 4-Cl

CH

3 0 3-CH 3 , 5-Cl 3-trfluoromethyl-2-pyridinyl 4-Br

CH

3 0 3-Br, 5-Cl 3-trifluoromethyl-2-pyridifyl 4-Br

CH

3 0 3-Br, 5-Br 3-trifluoromethyl-2-pyridinyl 4-Br

CH

3 0 3-CH 3 , 5-CN 3-trifluoromethyl-2-pyridifyl 4-Br

CH

3 0 3-CH 3 , 5-Cl 3-trifluoromethyl-2-pyridifyl 4-CF 3

CH

3 0 3-Br, 5-Cl 3-trifluoromethyl-2-pyridinyl 4-CF 3

CH

3 0 3-Br, 5-Br 3-trifluoromethyl-2-pyridinyl 4-CF 3

CH

3 0 3-CH 3 , 5-CN 3-trifluoromethyl-2-pyridinyl 4-CF 3 .256 Table 72 R6(R A 32 R - (R 14a

CH

3 0 3-CH 3 , 5-Cl 3-cyano-2-pyridifyl H

CH

3 0 3-Br, 5-Cl 3-cyano-2-pyridinyl H CH3 H0 3-Br, 5-Br 3-cyano-2-pyridifyl H

CH

3 0 3-CH3, 5-CN 3-cyano-2-pyridinyl H

CH

3 0 3-CE 3 , 5-Cl 3-cyano-2-pyridifyl 4-Cl

CH

3 0 3-Br, 5-Cl 3-cyano-2-pyridifyl 4-Cl

CH

3 0 3-Br, 5-Br 3-cyano-2-pyridinyl 4-Cl

CH

3 0 3-CH 3 , 5-CN 3-cyano-2-pyridinyl 4-Cl

CH

3 0 3-C~ 3 , 5-Cl 3-cyano-2-pyridinyl 4-Br

CH

3 0 3-Br, 5-Cl 3-cyano-2-pyridinyl 4-Br

CH

3 0 3-Br, 5-Br 3-cyano-2-pyridinyl 4-Br

CH

3 0 3-CE 3 , 5-CN 3-cyano-2-pyridifyl 4-Br

CH

3 0 3-CE 3 , 5-Cl 3-cyano-2-pyr3.dinyl 4-CF 3

CH

3 0 3-Br, 5-Cl 3-cyano-2-pyridinyl 4-CF 3

CH

3 0 3-Br, 5-Br 3-cyano-2-pyridinyl 4-CF 3

CM

3 '0 3-CM 3 , 5-CM 3-cyano-2-pyridiiyl 4-CF 3

CM

3 0 3-CM 3 , 5-Cl 3-nitro-2-pyridinyl H

CH

3 0 3-Br, 5-Cl 3-nitro-2-pyridinyl H

CE

3 0 3-Br, 5-Br 3-nltro-2-pyr-dinfyl H

CM

3 0 3-CE 3 , 5-CM 3-nitro-2-pyridinyl H

CM

3 0 3-CH 3 , 5-Cl 3-nitro-2-pyridinyl 4-Cl

CM

3 0 3-Br, 5-Cl 3-nitro-2-pyridinyl 4-Cl

CM

3 0 3-Br, 5-Br 3-nltro-2-pyr-dinfyl 4-Cl

CE

3 .0 3-CE 3 , 5-CM 3-nitro-2-py idinyl 4-Cl

CM

3 0 3-CE 3 , 5-Cl 3-nitro-2-pyridinyl 4-Br

CM

3 0 3-Br, 5-Cl 3-nitro-2-pyridinyl 4-Br

CM

3 0 3-Br, 5-Br 3-nitro-2-pyridinyl 4-Br

CH

3 0 3-CM 3 , 5-ON 3-nltro-2-pyr3.dinyl 4-Br

CE

3 0 3-CE 3 , 5-Cl 3-nitro-2-pyridiflyl 4-CF 3

CH

3 0 3-Br, 5-Cl 3-nitro-2-pyridinyl 4-CF 3

C%

3 0 3-Br, 5-Br 3-nitro-2-pyridinyl 4-CF 3

CE

3 10 3-CM 3 , 5-ON 3-nitro-2-pyridinyl 4 -CF 3 257 Table 73

R

6

A

32

(R

4 )R R1 4 a)

CH

3 0 3-CH 3 , 5-Cl 2-chiorophefyl H

CH

3 0 3-Br, 5-Cl 2-chlorophefyl H

CH

3 0 3-Br, 5-Br 2-chorophefyl H

CH

3 0 3-CM 3 , 5-CN 2-chiorophenyl H

CH

3 0 3-CR 3 , 5-Cl 2-chiorophenyl 4-Cl

CM

3 0 3-Br, 5-Cl 2-chlorophenyl 4-C1

CH

3 10 3-Br, 5-Br 2-chiorophenyl 4-Cl

CR

3 0 3-CR 3 , 5-CN 2-chlorophenyl 4-Cl

CM

3 0 3-CH 3 , 5-Cl 2-chlorophenyl 4-Br

CH

3 0 3-Br, 5-Cl 2-chlorophenyl 4-Br

CH

3 0 3-Br, 5-Br 2-chiorophenyl 4-Br

CH

3 0 3-CH 3 , 5-CN 2-chiorophenyl 4-Br

CH

3 0 3-C 3 , 5-Cl 2-chiorophenyl 4-CF 3

CH

3 0 3-Br, 5-Cl 2-chorophenyl 4-CF 3

CH

3 0 3-Br, 5-Br 2-chiorophenyl 4-CF 3

CH

3 0 3-CR 3 , 5-CN 2-chlorophenyl 4-CF 3

CR

3 0o 3-CR 3 , 5-Cl 2,6-dichlorophenyl H

CH

3 0 3-Br, 5-Cl 2,6-dichiorophelyl H

CH

3 0 3-Br, 5-Br 2,6-d.chlorophenyl H

CR

3 0 3-CR 3 , 5-CN 2, 6-dichlorophenyl H

CM

3 0 3-CR 3 , 5-Cl 2,6-dichloropheflyl 4-Cl

CR

3 0 3-Br, 5-Cl 2,6-dichiorophenyl 4-Cl

CR

3 0 3-5r, 5-Br 2,6-dichlorophenyl 4-Cl

CH

3 0 3-CR 3 , 5-CN 2, 6-dichlorophenyl 4-Cl

CH

3 0 3-CR 3 , 5-Cl 2,6-dichlorophenyl 4-Br

CR

3 0 3-Br, 5-Cl 2,6-dichlorophenyl 4-Br

CR

3 0 3-Br, 5-Br 2,6-dichlorophenyl . 4-Br

CH

3 0 3-CR 3 , 5-CN 2,6-dichlorophenyl 4-Br

CH

3 0 3-CR 3 , 5-Cl 2,6-dichiorophenyl 4-CF 3

CR

3 0 3-Br, 5-Cl 2,6-dichloropheflyl 4-CF 3

CH

3 0 3-Br, 5-Br 2,6-dichlorophenyl 4-CF 3

CR

3 0 3-CM 3 , 5-CN 2, 6-dichiorophenyl _4-CF 3 *258 Table 74 R_____6__ A 32

RR

4 1 3 a- 2 (R 1 4 a

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H

CH

2

CH

3 0 13-Br, 5-Br 3-chloro-2-pyridinyl H

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl 4-Cl

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl 4-Cl

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl 4-Cl

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl 4-Cl

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl 4-Br

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyriciinyl 4-Br

CH

2

CH

3 0 3-Br,. 5-Br 3-chloro-2-pyridinyl 4-Br

CH

2

CH

3 0 3-CH 3 F 5-CN 3-chloro-2-pyridinyl 4-Br CH2CH 3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl 4-CF 3

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyrid2.nyl 4-CF 3

CH

2

CH

3 10 3-Br, 5-Br 3-chloro-2-pyridinyl 4-CF 3

CH

2

CH

3 ' 10 3-CH 3 , 5-CN I3-chloro-2-pyridinyl 4-CF 3 259 Table 74 continued R6 A32 (R 4 ) l 3 a-2 (Ria)

CH

3 0 3-Cl, 5- Cl 3-chloro-2-pyridinyl 4-F

CH

3 0 3-Cl, 5- C1 3-chloro-2-pyridinyl 4-I

CH

3 0 3-Cl, 5- Cl 3-chloro-2-pyridinyl 4-CH 3

CH

3 0 3-Cl, 5- C1 3-chloro-2-pyridinyl 5-Cl

CH

3 0 3-Cl, 5- Cl 3-chloro-2-pyridinyl 5-Br

CH

3 0 3-Cl, 5- Cl 3-chloro-2-pyridinyl 5-CF 3

CH

3 0 3-Cl, 5- Cl 3-chloro-2-pyridinyl 4,5-Cl 2

CH

3 0 3-Cl, 5- Cl 3-chloro-2-pyridinyl 4,5-Br 2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl 4-Cl, 5-Br

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl 4-Cl, 5-Br

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl 4-Cl, 5-Br

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl 4-Cl, 5-Br

CH

3 0 3-C1, 5- C1 3-chloro-2-pyridinyl 4-Cl, 5-Br

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl 4-Br, 5-Cl

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl 4-Br, 5-Cl

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl 4-Br, 5-Cl

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl 4-Br, 5-Cl

CH

3 0 3-Cl, 5- Cl 3-chloro-2-pyridinyl 4-Br, 5-Cl A compound represented by the formula (1-S): S4(-S)

(R

4 )- 2

N--N-G-OCH

3 6 A2 5 6 2 a wherein R 1 , R 2 , R 3 , (R 4 ), and (R1 4 a)p represent combinations shown in Table 75 to Table 82.

260 Table 75 R2 R3 (R') (R ) 4 a H CH 3 H 3-CH 3 , 5-Cl H H CH 3 H 3-Br, 5-Cl H H CH 3 H 3-Br, 5-Br H H OH 3 H 3-CH 3 , 5HCN H CH 3 H3-H 3 , 5-Cl 4-Cl H CH 3 H 3-Br, 5-Cl 4 -Cl H CH 3 H 3-Br, 5-Br 4-Cl H CH 3 H 3-CH 3 , 5-CN 4-Cl H CH 3 H 3-CH 3 , 5-Cl 4-Br H CH 3 H 3-Br, 5-Cl 4-Br H CH 3 H 3-Br, 5-Br 4-Br H CH 3 H 3-CH 3 , 5-CN 4-Br H CH 3 H 3-CH 3 , 5-Cl 4-CF 3 H CH 3 H 3-Br, 5-Cl 4-CF 3 H CH 3 H 3-Br, 5-Br 4-CF 3 H CH 3 H 3-CH 3 , 5-ON 4-CF 3 H H OH 3 3-OH 3 , 5-Cl H H H CH 3 3-Br, 5-Cl H H H CH 3 3-Br, 5-Br H H H OH 3 3-OH 3 , 5-ON H H H OH 3 3-OH 3 , 5-Cl 4-C1 H H OH 3 3-Br, 5-01 4-C1 H H CH 3 3-Br, 5-Br 4-Cl H H CH 3 3-CH 3 , 5-ON 4-Cl H H OH 3 3-OH 3 , 5-01 4-Br H H CH 3 3-Br, 5-Cl 4-Br H H CH 3 3-Br, 5-Br 4-Br H H CH 3 3-OH 3 , 5-ON 4-Br H H CH 3 3-OH 3 , 5-01 4-CF 3 H H OH 3 3-Br, 5-01 4-OF 3 H H CH 3 3-Br, 5-Br 4-CF 3 H CH 3 3-OH 3 , 5-ON 4-CF 3 261 Table 76

R

2

R

3

(R

4 ) R (R4a _ H CH 3

CH

3 3-CH 3 , 5-Cl H H CH 3

CH

3 3-Br, 5-Cl H H CH 3

CH

3 3-Br, 5-Br H H CH 3

CH

3 3-CH3, 5-CN H H CH 3

CH

3 3-CH 3 , 5-Cl 4-Cl H CH 3

CH

3 3-Br, 5-Cl 4-Cl H CH 3

CH

3 3-Br, 5-Br 4-C1 H CH 3

CR

3 3-CH 3 , 5-CN 4-Cl H CH 3

CH

3 3-CR 3 , 5-Cl 4-Br H CH 3

CH

3 3-Br, 5-Cl 4-Br H CH 3

CH

3 3-Br, 5-Br 4-Br H CH 3

CH

3 3-CH 3 , 5-CN 4-Br H CH 3

CH

3 3-CR 3 , 5-Cl 4-CF 3 H CH 3

CH

3 3-Br, 5-Cl 4-CF 3 H CH 3

CH

3 3-Br, 5-Br 4-CF 3 H CH 3

CH

3 3-CH 3 , 5-CN 4-CF 3 H H CH 2

CH

3 3-CH 3 , 5-Cl H H H CH 2

CH

3 3-Br, 5-Cl H H H CH 2

CH

3 3-Br, 5-Br H H H CH 2

CH

3 3-CR 3 , 5-CN H H H CH 2

CH

3 3-CR 3 , 5-Cl 4-Cl H H CH 2

CH

3 3-Br, 5-Cl 4-Cl H H CH 2

CH

3 3-Br, 5-Br 4-Cl H H CH 2

CH

3 3-CH 3 , 5-CN 4-Cl H H CH 2

CH

3 3-CR 3 , 5-Cl 4-Br H H CH 2

CH

3 3-Br, 5-Cl 4-Br H H CH 2

CH

3 3-Br, 5-Br 4-Br H H CH 2

CH

3 3-CR 3 , 5-CN 4-Br H H CH 2

CH

3 3-CH 3 , 5-Cl 4-CF 3 H H CH 2

CH

3 3-Br, 5-Cl 4-CF 3 H H CH 2

CH

3 3-Br, 5-Br 4-CF 3 H H CH 2

CH

3 3-CH 3 , 5-CN 4-CF 3 262 Table 77 R_2 R3 (R') (R1 4 a H H CH(CH 3

)

2 3-CH 3 , 5-Cl H H H CH (CH 3 ) 2 3-Br, 5-Cl H H IH CH (CH 3 ) 2 3-Br, 5-Br H H H CH (CH 3 ) 2 3-CH 3 , 5-CN H H H CH (CH 3 ) 3-CH 3 , 5-Cl 4-Cl H H CH(CH 3

)

2 3-Br, 5-Cl 4-Cl H H CH(CH 3

)

2 3-Br, 5-Br 4-Cl H H CH (CH 3 ) 2 3-CH 3 , 5-CN 4-Cl H H CH(CH 3

)

2 3-CH 3 , 5-Cl 4-Br H H CH (CH 3 ) 2 3-Br, 5-Cl 4 -Br H H CH(CH 3

)

2 3-Br, 5-Br 4 -Br H H CH (CH 3 ) 2 3-CH 3 5-CN 4-Br H H CH (CH 3

)

2 3-CH 3 , 5-Cl 4-CF 3 H H CH (CH 3 ) 2 3-Br, 5-Cl 4-CF 3 H H CH (CH 3

)

2 3-Br, 5-Br 4-CF 3 H H CH (CH 3 ) 2 3-CH 3 , 5-CN 4-CF 3 H H C(CH 3

)

3 3-CH 3 , 5-Cl H H H C (CH 3 ) 3 3-Br, 5-Cl H H H C(CH 3

)

3 3-Br, 5-Br H H H C(CH 3

)

3 3-CH 3 , 5-CN H H H C(CH 3

)

3 3-CH 3 , 5-Cl 4-Cl H H C (CH 3 ) 3 3-Br, 5-Cl 4 -Cl H H C (CH 3 ) 3 3-Br, 5-Br 4-Cl H H C(CH 3

)

3 3-CH 3 , 5-CN 4-Cl H H C(CH 3

)

3 3-CH 3 1 5-Cl 4-Br H H C(CH 3

)

3 3-Br, 5-Cl 4-Br H H C (CH 3 ) 3 3-Br, 5-Br 4 -Br H H C (CH 3

)

3 3-CH 3 , 5-CN 4-Br H H C(CH 3

)

3 3-CH 3 , 5-Cl 4-CF 3 H H C(CH 3

)

3 3-Br, 5-Cl 4-CF 3 H H C (CH 3 ) 3 3-Br, 5-Br 4 -CF 3 H H C(CH 3

)

3 3-CH 3 , 5-CN 4-CF 3 .263 Table 78 R_ R2 R3 (R_)(R1 4 a) H H C(=O)OCH 3 3-CH 3 , 5-Cl H H H C(=O)OCH 3 3-Br, 5-Cl H H H C(=O)OCH 3 3-Br, 5-Br H H H C(=O)OCH3 3-CH 3 , 5-CN H H H C(=O)OCH 3 3-CH 3 , 5-Cl 4-Cl H H C (=O) OCH 3 3-Br, 5-Cl 4-Cl H H C(=O)OCH 3 3-Br, 5-Br 4-Cl H H C(=O)OCH 3 3-CH 3 , 5-CN 4-Cl H H C(=O)OCH 3 3-CH 3 , 5-Cl 4-Br H H C(=O)OCH 3 3-Br, 5-Cl 4-Br H H C(=O)OCH 3 3-Br, 5-Br 4-Br H H C(=O)OCH 3 3-CH 3 , 5-CN 4-Br H H C(=O)OCH 3 3-CH 3 , 5-Cl 4-CF 3 H H C(=O)OCH 3 3-Br, 5-Cl 4-CF 3 H H C (=O) OCH 3 3-Br, 5-Br 4-CF 3 H H C(=O)OCH 3 3-CH 3 , 5-CN 4-CF 3 H H C(=O)N(CH 3

)

2 3-CH 3 , 5-Cl H H H C(=O)N(CH 3

)

2 3-Br, 5-Cl H H H C(=O)N(CH 3

)

2 3-Br, 5-Br H H H C(=O)N(CH 3

)

2 3-CH 3 , 5-CN H H H C(=O)N(CH 3

)

2 3-CH 3 , 5-Cl 4-Cl H H C(=O)N(CH 3

)

2 3-Br, 5-Cl 4-Cl H H C(=O)N(CH 3

)

2 3-Br, 5-Br 4-Cl H H C(=O)N(CH 3

)

2 3-CH 3 , 5-CN 4-Cl H H C(=O)N(CH 3

)

2 3-CH 3 , 5-Cl 4-Br H H C(=O)N(CH 3

)

2 3-Br, 5-Cl 4-Br H H C(=O)N(CH 3

)

2 3-Br, 5-Br 4-Br H H C(=O)N(CH 3

)

2 3-CH 3 , 5-CN 4-Br H H C(=O)N(CH 3

)

2 3-CH 3 , 5-cl 4-CF 3 H H C(=O)N(CH 3

)

2 3-Br, 5-Cl 4-CF 3 H H C(=O)N(CH 3

)

2 3-Br, 5-Br 4-CF 3 H H C(=O)N(CH 3

)

2 3-CH 3 , 5-CN 4-CF 3 264 Table 79 Ri R2 R 3 (R4), (R 14 a

CH

3

CH

3 H 3-CH 3 , 5-Cl H

CH

3

CH

3 H 3-Br, 5-Cl H

CH

3

CH

3 H 3-Br, 5-Br H

CH

3

CH

3 H 3-CH 3 , 5-CN H

CH

3

CH

3 H 3-CH 3 , 5-Cl 4-Cl

CH

3

CH

3 H 3-Br, 5-Cl 4-Cl

CH

3

CH

3 H 3-Br, 5-Br 4-Cl

CH

3

CH

3 H 3-CH 3 , 5-CN 4-Cl

CH

3

CH

3 H 3-CH 3 , 5-Cl 4-Br

CH

3

CH

3 H 3-Br, 5-Cl 4-Br

CH

3

CH

3 H 3-Br, 5-Br 4-Br

CH

3

CH

3 H 3-CH 3 , 5-CN 4-Br

CH

3

CH

3 H 3-CH 3 , 5-Cl 4-CF 3

CH

3

CH

3 H 3-Br, 5-Cl 4-CF 3

CH

3

CH

3 H 3-Br, 5-Br 4-CF 3

CH

3

CH

3 H 3-CH 3 , 5-CN 4-CF 3

CH

3 H CH 3 3-CH 3 , 5-Cl H

CH

3 H CH 3 3-Br, 5-Cl H

CH

3 H CH 3 3-Br, 5-Br H

CH

3 H CH 3 3-CH 3 , 5-CN H

CH

3 H CH 3 3-CH 3 , 5-Cl 4-Cl

CH

3 H CH 3 3-Br, 5-Cl 4-Cl

CH

3 H CH 3 3-Br, 5-Br 4-Cl

CH

3 H CH 3 3-CH 3 , 5-CN 4-Cl

CH

3 H CH 3 3-CH 3 , 5-Cl 4-Br

CH

3 H CH 3 3-Br, 5-Cl 4-Br

CH

3 H CH 3 3-Br, 5-Br 4-Br

CH

3 H CH 3 3-CH 3 , 5-CN 4-Br

CH

3 H CH 3 3-CH 3 , 5-Cl 4-CF 3

CH

3 H CH 3 3-Br, 5-Cl 4-CF 3

CH

3 H CH3 3-Br, 5-Br 4-CF 3 CH3 H CH 3 3-CH 3 , 5-CN 4-CF 3 .265 Table 80 R_ R 2 R3 (Rta)

CH

3

CH

3

CH

3 3-CH 3 , 5-Cl H CH3 CH 3

CH

3 3-Br, 5-Cl H

CH

3

CH

3

CH

3 3-Br, 5-Br H

CH

3

CH

3

OH

3 3-CH 3 5-CN H CH3 CH 3 C 3-OH 3 , 5-Cl 4-Cl CH3 CH 3

CH

3 3-Br, 5-Cl 4-Cl

CH

3

CH

3

CH

3 3-Br, 5-Br 4-Cl

CH

3

CH

3

CH

3 3-CH 3 , 5-CN 4-Cl

CH

3 083 OH 3 3-OH 3 , 5-Cl 4-Br

CH

3

CH

3 083 3-Br, 5-Cl 4-Br

CH

3

CH

3

CH

3 3-Br, 5-Br 4-Br CH3 CH3 CH 3 3-OH 3 , 5-ON 4-Br

CH

3

CH

3

CH

3 3-OH 3 , 5-01 4-CF 3 CH3 CH 3 CH3 3-Br, 5-01 4-CF 3 CH3 CH3 CH3 3-Br, 5-Br 4-CF 3

CH

3 083 CH3 3-083, 50N 4-CF 3

CH

3 H CH2CH3 3-083, 5-01 H

CH

3 H CH2CH3 3-Br, 5-Cl H CH3 H CH2CH3 3-Br, 5-Br H CH3 H CH2CH3 3-083, 5-ON H CH3 H CH2CH3 3-083, 501 4-C1

CH

3 H CH2CH3 3-Br, 5-Cl 4-Cl CH3 H 082083 3-Br, 5-Br 4-Cl CH3 H CH2CH3 3-CH3, 5-CN 4-01

CH

3 H CH 2

CH

3 3-CH3, 5-Cl 4-Br CH3 H CH2CH3 3-Br, 5-Cl 4-Br CH3 H CH2CH3 3-Br, 5-Br 4-Br CH3 H CH2CH3 3-083, 5-ON 4-Br CH3 H CH2CH3 3-03, 501 4-CF 3 083 H CH2CH3 3-Br, 5-Cl 4-CF 3 CH3 H CH2CH3 3-Br, 5-Br 4-CF 3 CH3 H CH2CH3 3-03, 5-ON 4-CF 3 ,266 Table 81 RR2R 3 (R')Rl 4 a)~

CH

3 H CH (CH 3 ) 2 3-CH 3 , 5-Cl H

CH

3 H CH(CH 3

)

2 3-Br, 5-Cl H CH3 H CH(CH 3

)

2 3-Br, 5-Br H

CH

3 H CH (CH 3

)

2 3-CH 3 , 5-CN H

CH

3 H CH (CH 3

)

2 3-CH 3 , 5-Cl 4-Cl

CH

3 H CH (CH 3 ) 2 3-Br, 5-Cl 4-Cl

CH

3 H CH (CH 3 ) 2 3-Br, 5-Br 4-Cl

CH

3 H CH (CH 3 ) 2 3-CH 3 , 5-CN 4-Cl

CR

3 H CH(CH 3

)

2 3-CH 3 , 5-Cl 4-Br

CH

3 H CH(CH 3

)

2 3-Br, 5-Cl 4-Br

CH

3 H CH (CH 3 ) 2 3-Br, 5-Br 4 -Br

CH

3 H CH(CH 3

)

2 3-CH 3 , 5-CN 4-Br

CH

3 H CH(CH 3

)

2 3-CH 3 , 5-Cl 4-CF 3

CH

3 H CH(CH 3

)

2 3-Br, 5-Cl 4-CF 3

CH

3 H CH (CH 2 3-Br, 5-Br 4-CF 3

CH

3 H CH (CH 3 ) 2 3-CH 3 , 5-CN 4-CF 3

CH

3 H C (CH 3 ) 3 3-CR 3 , 5-Cl H

CH

3 H C (CHD) 3 3-Br, 5-Cl H

CH

3 H C (CH 3 ) 3 3-Br, 5-Br H

CH

3 H C (CH 3 ) 3 3-CR 3 , 5-CN H

CH

3 H C (CH 3 ) 3 3-CH 3 , 5-Cl_ 4-Cl

CH

3 H C (CHD) 3 3-Br, 5-Cl 4-Cl

CH

3 H C (CHD) 3 3-Br, 5-Br 4-Cl

CH

3 H C (CHD) 3 3-CH 3 , 5-CN 4 -Cl

CH

3 H C (CH 3 ) 3 3-CH 3 , 5-Cl 4-Br

CH

3 H C (CH 3 ) 3 3-Br, 5-Cl 4 -Br

CH

3 H C (CH 3 ) 3 3-Br, 5-Br 4-Br

CH

3 H C (CR 3 ) 3 3-CR 3 , 5-CN 4 -Br

CR

3 H C (CHD) 3 3-CH 3 , 5-Cl 4-CF 3

CH

3 H C (CH 3 ) 3 3-Br, 5-Cl 4-CF 3

CR

3 H C (CH 3 ) 3 3-Br, 5-Br 4-CF 3

CH

3 H C (CH 3 ) 3 3-CH 3 , 5-CN 4-CF 3 ,267 Table 82 RiR2R 3 (R__) __, (R 1 4 a p

CH

3 H C (=O) OCH 3 3-CH 3 , 5-Cl H

CH

3 H C (=0) OCH 3 3-Br, 5-Cl H

CH

3 H C(=O)OCH 3 3-Br, 5-Br H

CH

3 H C(=O)OCH 3 3-CM 3 , 5-CN H

CH

3 H C (=O) QCH 3 3-CH 3 , 5-Cl 4 -Cl

CH

3 H C (=O) OCH 3 3-Br, 5-Cl 4 -Cl

CM

3 H C (=O) OCH 3 3-Br, 5-Br 4-Cl

CH

3 H C (=O) OCH 3 3-CM 3 , 5-CN 4 -Cl

CM

3 H C(=O)OCH 3 3-CH 3 , 5-Cl 4 -Br

CH

3 H C (=0) OCH 3 3-Br, 5-Cl 4 -Br

CM

3 H C (=O) OCM 3 3-Br, 5-Br 4 -Br

CH

3 H C (=O) OCH 3 3-CH 3 , 5-CN 4 -Br

CH

3 H C (=O) OCH 3 3-CH 3 , 5-Cl 4-CF 3

CH

3 H C (=O) OCH 3 3-Br, 5-Cl 4 -CF 3

CM

3 H C (=O) CH 3 3-Br, 5-Br 4 -CF 3

CH

3 H C (=O) OCH 3 3 -CM 3 ,F 5-CN 4-CF 3

CM

3 H C (=O) N(CH 3 ) 2 3-CM 3 , 5-Cl H

CM

3 H C (=O)N (CH 3 ) 2 3-Br, 5-Cl H

CM

3 H C (=0) N(CH 3

)

2 3-Br, 5-Br H

CH

3 H C (=) N(CH 3 ) 2 3-CM 3 , 5-CN H

CM

3 H C (=O) N(CH 3 ) 2 3-CM 3 , 5-Cl 4-Cl

CH

3 H C (=)N(CH 3 ) 2 3-Br, 5-Cl 4-Cl

CM

3 H C (=O) N(CH 3 ) 2 3-Br, 5-Br 4-Cl

CH

3 H C (=O) N(CM 3 ) 2 3-CM 3 , 5-CN 4-Cl

CM

3 H C (=-) N (CH 3 ) 2 3-CM 3 , 5-Cl 4-Br

CM

3 H C (=O) N(CH 3 ) 2 3-Br, 5-Cl 4 -Br

CH

3 H C (=O)N(CH 3 ) 2 3-Br, 5-Br 4-Br

CH

3 H C (=O) N(CH 3

)

2 -3-CM 3 , 5-CN 4 -Br

CM

3 H C (=O) N(CH 3 ) 3-CM 3 , 5-Cl 4-CF 3

CM

3 H C (=O) N(CH 3 ) 2 3-Br, 5-Cl 4-CF 3

CM

3 H C (=O) N(CH 3 ) 2 3-Br, 5-Br 4-CF 3

CM

3 H C (=O) N(CM 3 ) 2 3-CM 3 , 5-CN 4-CF 3 268 Table 82 continued H CH 3 H 3-Cl, 5-Cl H H CH 3 H 3-Cl, 5-Cl 4-C1, H CH 3 H 3-Cl, 5-Cl 4-Br H CH 3 H 3-Cl, 5-Cl 4-CF 3 H CE 3 H 3-Cl, 5-Cl 4 ,5-Cl 2 H CH 3 H 3-Cl, 5-Cl 4,5-Br 2 H CH 3 H 3-CH 3 , 5-Cl 4-Cl, 5-Br H

CE

3 H 3-Br, 5-Cl 4-Cl, 5-Br H

CH

3 H 3-Br, 5-Br 4-Cl, 5-Br H

CE

3 H 3-CH 3 , 5-CN 4-Cl, 5-Br H

CH

3 H 3-C1, 5-Cl 4-Cl, 5-Br H CE 3 H 3-CH 3 , 5-Cl 4-Br, 5-Cl H

CE

3 H 3-Br, 5-Cl 4 -Br, 5-Cl H

CE

3 H 3-Br, 5-Br 4-Br, 5-Cl H

CH

3 H 3-CE 3 , 5-CN 4-Br, 5-Cl H

CE

3 H 3-Cl, 5-Cl 4-Br, 5-Cl H H CH 3 3-Cl, 5-Cl H H H CE 3 3-Cl, 5-Cl 4-Cl H H CE 3 3-Cl, 5-Cl 4-Br H. H CE 3 3-Cl, 5-Cl 4-CF 3 H H CE 3 3-Cl, 5-Cl 4,5-Cl 2 H H CE 3 3-Cl, 5-Cl 4,5-Br 2 H H CH 3 3-CE 3 , 5-Cl 4-Cl, 5-Br H H

CE

3 3-Br, 5-Cl 4-Cl, 5-Br H H

CE

3 3-Br, 5-Br 4-Cl, 5-Br H H

CE

3 3-CH 3 , 5-CN 4-Cl, 5-Br H H

CH

3 3-Cl, 5-Cl 4-Cl, 5-Br H H

CE

3 3-CE 3 , 5-Cl 4-Br, 5-Cl H H

CH

3 3-Br, 5-Cl 4-Br, 5-Cl H H

CE

3 3-Br, 5-Br 4-Br, 5-Cl H H CE 3 3-CE 3 , 5-CN 4-Br, 5-Cl H IH

CH

3 I3-Cl, 5-Cl I4-Br, 5-Cl 269 Table 82 continued Ri R 2 R3(R)R1a H CM 3

CH

3 3-Cl, 5-Cl H H CH 3

CH

3 3-Cl, 5-Cl 4-Cl H CH 3

CM

3 3-Cl, 5-Cl 4-Br H CH 3

CH

3 3-Cl, 5-Cl 4-CF 3 H CM 3

CH

3 t 3-Cl, 5-Cl 4,5-Cl 2 H CH 3

CH

3 3-Cl, 5-Cl 4,5-Br 2 H CM 3

CH

3 3-CH 3 , 5-Ci 4-Cl, 5-Br H CH 3

CM

3 3-Br, 5-Cl 4-Cl, 5-Br H CH 3

CM

3 3-Br, 5-Br 4-Cl, 5-Br H

CM

3

CM

3 3-CM 3 , 5-CN 4-Cl, 5-Br H CM 3

CM

3 3-Cl, 5-Cl 4-Cl, 5-Br H CH 3

CM

3 3-CM 3 , 5-Cl 4-Br, 5-Cl H C 3

CH

3 3-Br, 5-Cl 4-Br, 5-Cl H CM 3

CH

3 3-Br, 5-Br 4-Br, 5-Cl H CM 3

CM

3 3-CH 3 , 5-CN 4-Br, 5-Cl, H

CM

3

CM

3 3-Cl, 5-Cl 4-Br, 5-cl H H CH 2

CH

3 3-C1, 5-Cl H H H CH 2

CH

3 3-Cl, 5-Cl 4-Cl H H CH 2

CH

3 3-Cl, 5-Cl 4-Br H H CH 2

CH

3 3-Cl, 5-Cl 4-CF 3 H H CHM(CH 3 ) 2 3-Cl, 5-Cl H H H CH (CH 3 ) 2 3-Cl, 5-Cl 4-C1 H H CH (CH 3 ) 2 3-Cl, 5-Cl 4-Br H H CH (CH 3 ) 2 3-Cl, 5-Cl 4-CF 3 H H C (CH 3 ) 3 3-Cl, 5-Cl H H H C (CH 3 ) 3 3-Cl, 5-Cl 4-Cl H IH C (CH 3 ) 3 3-Cl, 5-Cl 4-Br H IH C (CH 3 ) 3 3-Cl, 5-Cl 4-CF 3 .270 Table 82 continued R_2 R_ (R) (R 4 a) p H H C(=O)OCH 3 3-C1, 5-Cl H H H C(=O)OCH 3 3-Cl, 5-Cl 4-Cl H H C(=O)OCH 3 3-Cl, 5-Cl 4-Br H H C(=O)OCH 3 3-Cl, 5-Cl 4-CF 3 H H C(=0)N(CH 3

)

2 3-Cl, 5-Cl H H H C(=O)N(CH 3

)

2 3-C1, 5-Cl 4-Cl H H C(=O)N(CH 3

)

2 3-Cl, 5-Cl 4-Br H H C(=O)N(CH 3 )2 3-Cl, 5-Cl 4-CF 3

CH

3

CH

3 H 3-Cl, 5-Cl H

CH

3

CH

3 H 3-Cl, 5-Cl 4-Cl CH3 CH 3 H 3-Cl, 5-Cl 4-Br

CH

3

CH

3 H 3-Cl, 5-Cl 4-CF 3

CH

3 H CH 3 3-Cl, 5-Cl H

CH

3 H

CH

3 3-Cl, 5-Cl 4-Cl

CH

3 H CH 3 3-Cl, 5-Cl 4-Br

CH

3 H CH 3 3-Cl, 5-Cl 4-CF 3

CH

3

CH

3

CH

3 3-Cl, 5-Cl H

CH

3

CH

3

CH

3 3-Cl, 5-Cl 4-Cl

CH

3

CH

3

CH

3 3-Cl, 5-Cl 4-Br

CH

3

CH

3

CH

3 3-C1, 5-Cl 4-CF 3

CH

3 H

CH

2

CH

3 3-Cl, 5-Cl H

CH

3 H CH 2

CH

3 3-C1, 5-Cl 4-Cl

CH

3 H

CH

2

CH

3 3-C1, 5-Cl 4-Br

CH

3 H CH 2

CH

3 3-Cl, 5-Cl 4-CF 3

CH

3 H CH(CH 3

)

2 3-Cl, 5-Cl H CH 3 H CH(CH 3

)

2 3-C1, 5-Cl 4-Cl

CH

3 H CH(CH 3

)

2 3-Cl, 5-Cl 4-Br

CH

3 H CH(CH 3

)

2 3-C1, 5-Cl 4-CF 3

CH

3 H C(CH 3

)

3 3-Cl, 5-Cl H

CH

3 H C(CH 3

)

3 3-Cl, 5-Cl 4-Cl

CH

3 H C(CH 3

)

3 3-Cl, 5-Cl 4-Br

CH

3 H C(CH 3

)

3 3-Cl, 5-Cl 4-CF 3 .271 Table 82 continued Ri R 2 R 3 (R4)n )(Ria

CH

3 H C(=O)OCH 3 3-C1, 5-Cl H

CH

3 H C (=O) OCH 3 3-Cl, 5-Cl 4-C1

CH

3 H C(=O)OCH 3 3-C1, 5-Cl 4-Br

CH

3 H C(=O)OCH 3 3-Cl, 5-Cl 4-CF 3

CH

3 H C (=O),N (CH 3 ) 2 3-Cl, 5-Cl H

CH

3 H C (=0) N (CH 3 ) 2 3-C1, 5-Cl 4-Cl

CH

3 H C (=O) N (CH 3 ) 2 3-Cl, 5-Cl 4-Br

CH

3 H C(=O)N(CH 3 )2 3-Cl, 5-Cl 4-CF 3 ,272 A compound represented by the formula (1-I): 14a . 5i N 3 ,Z R 1a-2( ) (R 4)n-- 6 NH-NH NR'R' wherein NR 8

R

9 , A 34 , (R 4 )n, R 13 2 and (R1 4 a), represent combinations shown in Table 83. 5 Table 83

NRBR

9

A

3 4 (R4)n R a 13 -2 (R14a)P N (CH 3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl H

N(CH

3

)

2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl H N (CH 3 ) 2 0 3-Br, 5-Br 3-chloro-2-pyridinyl H N (CH 3 ) 2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

N(CH

3

)

2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl 4-Cl N (CH 3 ) 2 , 0 3-Br, 5-Cl 3-chloro-2-pyridinyl 4-Cl

N(CH

3

)

2 0 3-Br, 5-Br 3-chloro-2-pyridinyl 4-Cl

N(CH

3 )2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl 4-Cl

N(CH

3

)

2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl 4-Br N (CH 3 ) 2 0 3-Br,' 5-Cl 3-chloro-2-pyridinyl 4-Br

N(CH

3

)

2 0 3-Br, 5-Br 3-chloro-2-pyridinyl 4-Br N (CH 3 ) 2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl 4-Br N (CH 3 ) 2 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinyl 4-CF 3 N (CH 3 ) 2 0 3-Br, 5-Cl 3-chloro-2-pyridinyl 4,-CF 3 N (CH 3 ) 2 0 3-Br, 5-Br 3-chloro-2-pyridinyl 4-CF 3

N(CH

3

)

2 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl 4-CF 3 273 A compound represented by the formula (1-K): R1 4 a-3 N\ N 4 3 0 H 13a-3(l- ) (R 4)- H 6 _H-NH-TOR6 1133 3213-3 wherein R 6 , A32, (R 4 ),, Rl 3 a- 3 and R1 4 a 3 represent combinations shown in Table 84.

274 Table 84 R 6 A 32

R

4

R

13 a -3 R1 4 a-3

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdinfyl H

CH

3 0 3-Br, 5-Cl 3-chloro-2-PYrldlflyl H

CH

3 0 3-Br, 5-Br 3-chjloro-2-pyridlflyl H

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyrldlflyl H

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyri3.flyl -cl

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl Cl

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridflyl Cl

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridlrlyl Cl

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl Br

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridflyl Br

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridlflyl Br

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridlflyl Br

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlrlyl

CF

3

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl

CF

3

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridflyl

CF

3

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinfyl

CF

3

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyr-dnyl H

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyrldlflyl H

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridlflyl H

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinyl H

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridilYl Cl

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl Cl

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridinyl Cl

CH

2

CH

3 0 3-CH 3 r 5-CN 3-chloro-2-pyridiflyl Cl

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl Br

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl Br

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridilyl Br

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinfyl Br

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl

CF

3

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl

CF

3

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridlflyl

CF

3

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro-2-pyridinfyl

CF

,275 A compound represented by the formula (1-N): R 148-4 N N ,N 34 NH 13.4 (1N (Ra 4 n 2 I -NH-NH -R' 6 13 wherein R 6 , A 3 2 , (R 4 )n, Ria- 4 and R 1 4 a- 4 represent combinations shown in Table 85.

,276 Table 85 R6A 32 (R 4 ) R 13 a- 4 R4

CH

3 0 3-CM 3 , 5-Cl 3-chloro-2-pyrdinfyl H

CM

3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl H

CH

3 0 3-Br, 5-Br 3-chloro-2-pyr3.dinfl H

CO

3 0 3-CH - - -chloro-2-pyrid -yl H

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridinfyl C1

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyr-dinfll C1

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridiflyl Cl

CH

3 0 3-CH 3 , 5-CM 3-chloro-2-pyrin-dyl Cl

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridiflyl Br

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyr3-diflyl Br

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridlflyl Br

CH

3 0 3-CH 3 1 5-CM 3-chloro-2-pyridlflyl Br

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl

CF

3

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridiflyl

CF

3

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridiriyl

CF

3

CH

3 0 3-CH 3 , 5-CM 3-chloro-2-pyridiflyl

CF

3

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridlflyl H

CH

2

CH

3 0 3-Br, 5-Cl 3-choro-2pyridnyl H

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridilJ H

CH

2

CH

3 0 3-CH 3 , 5-CM 3-chloro-2-pyrid3.nyl H

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyridilyl Cl

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridlflyl Cl

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridiflyl Cl

CH

2

CH

3 0 3-CM 3 , 5-CM 3-chloro-2-pyridilyl C1

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro-2-pyrdinfyl Br

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridinyl Br

CH

2

CH

3 0 3-Br, 5-Br 3-chloro-2-pyridiflyl Br

CH

2

CH

3 0 3-CH 3 , 5-CM 3-chloro-2-pyridinyl Br

CH

2

CH

3 0 3-CM 3 , 5-Cl 3-chloro-2-pyridlflyl

CF

3

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro-2-pyridflyl

CF

3

CH

2 CH, 0 13-Br, 5-Br 3-chloro-2-pyridlflyl

CF

3

CH

2

CH

3 0 13-CM 3 , 5-CM 3-chloro-2-pyrdinfyl

ICF

3 ,277 A compound represented by the formula (1-Q): R 14by-1 ,oj 'N-R13b-1 3 14bz-1 (I-Q) 4H 1 NH (R 4)n | 126 1 -NH-NHrRe 6 13 0 wherein R 6 , A 32 , (R 4 )n, R 1b-, R 14- and Rl 4 by1 represent combinations shown in Table 86 to Table 89.

.278 Table 86

R

6

A

3 2

(R

4 )n R1 4 bz-1 Ri 4 by-1 R13b-1

CH

3 0 3-CH 3 , 5-Cl 2-chlorophenyl H

CH

3

CH

3 0 3-Br, 5-Cl 2-chlorophenyl H

CH

3

CH

3 0 3-Br, 5-Br 2-chlorophenyl H

CH

3

CH

3 0 3-CH 3 , 5-CN 2-chlorophenyl H CH3

CH

3 0 3-CH 3 , 5-Cl 3-chloro- H

CH

3 2-pyridinyl

CH

3 0 3-Br, 5-Cl 3-chloro- H CH3 2-pyridinyl

CH

3 0 3-Br,. 5-Br 3-chloro- H

CH

3 2-pyridinyl

CH

3 0 3-CH 3 , 5-CN 3-chloro- H CH3 2-pyridinyl

CH

3 0 3-CH 3 , 5-Cl H 2-chlorophenyl

CH

3

CH

3 0 3-Br, 5-Cl H 2-chlorophenyl CH3

CH

3 0 3-Br, 5-Br H 2-chlorophenyl CH3

CH

3 0 3-CH 3 , 5-CN H 2-chlorophenyl CH3

CH

3 0 3-CM 3 , 5-Cl H 3-chloro-2-pyridinyl CH3

CH

3 0 3-Br, 5-Cl H 3-chloro-2-pyridinyl

CH

3

CH

3 0 3-Br, 5-Br H 3-chloro-2-pyridinyl CH3

CH

3 0 3-CH 3 , 5-CN H 3-chloro-2-pyridinyl

CH

3

CH

3 0 3-CH 3 , 5-Cl 2-chlorophenyl, H

C(CH

3

)

3 C3 3 0 3-Br, 5-Cl 2-chlorophenyl H C (CH 3 ) 3

CH

3 0 3-Br, 5-Br 2-chlorophenyl H

C(CH

3

)

3

C

3 0 13-CH 3 , 5-CN 2-chlorophenyl H

C(CH

3

)

3

CH

3 0 3-CH 3 , 5-Cl 3-chloro- H C(CH 3

)

3 2-pyridinyl

CH

3 0 3-Br, 5-Cl 3-chloro- H . C(CH 3

)

3 2-pyridinyl

CH

3 0 3-Br, 5-Br 3-chloro- H

C(CH

3

)

3 2-pyridinyl

CH

3 0 3-CH 3 , 5-CN 3-chloro- H C(CH 3

)

3 2-pyridinyl

CM

3 0 3-CH 3 , 5-Cl H 2-chlorophenyl C(CH 3

)

3

CH

3 0 3-Br, 5-Cl H 2-chlorophenyl C(CH3) 3

CH

3 0 3-Br, 5-Br H 2-chlorophenyl

C(CH

3

)

3

CH

3 0 3-CH 3 , 5-CN H 2-chlorophenyl

C(CH

3

)

3

CH

3 0 3-CH 3 , 5-Cl H 3-chloro-2-pyridinyl C (CH 3 ) 3

CH

3 0 3-Br, 5-Cl H 3-chloro-2-pyridinyl

C(CH

3

)

3

CH

3 0 3-Br, 5-Br H 3-chloro-2-pyridinyl

C(CH

3

)

3

CH

3 0 3-CH 3 , 5-CN H 3-chloro-2-pyridinyl

C(CH

3

)

3 .279 Table 87 A" (R 4 ) n Ri_ _z-1__R___- R

CH

3 0 3-CH 3 , 5-Cl 2-chlorophenyl H CH 2

CF

3

CH

3 0 3-Br, 5-Cl 2-chlorophenyl H CH2CF3

CH

3 0 3-Br, 5-Br 2-chlorophenyl H

CH

2 CF3

CH

3 0 3-CH 3 , 5-CN 2-chlorophenyl H

CH

2

CF

3

CH

3 0 3-CH 3 , 5-Cl 3-chioro- H

CH

2

CF

3 2-pyridinyl

CH

3 0 3-Br, 5-Cl 3-chloro- H

CH

2

CF

3 , 2-pyridinyl

CH

3 0 3-Br, 5-Br 3-chioro- H

CH

2

CF

3 2-pyridinyl

CH

3 0 3-CH 3 , 5-CN 3-chloro- H

CH

2

CF

3 2-pyridinyl

CH

3 0 3-CH 3 , 5-Cl H 2-chlorophenyl

CH

2

CF

3

CH

3 0 3-Br, 5-Cl H 2-chlorophenyl

CH

2

CF

3

CH

3 0 3-Br, 5-Br H 2-chlorophenyl

CH

2 CF3

CH

3 0 3-CH 3 , 5-CN H 2-chlorophenyl

CH

2

CF

3

CH

3 0 3-CH 3 , 5-Cl H 3-chloro-

CH

2

CF

3 2-pyridinyl

CH

3 0 3-Br, 5-Cl H 3-chloro-

CH

2

CF

3 2-pyridinyl

CH

3 0 3-Br, 5-Br H 3-chloro-

CH

2

CF

3 2-pyridinyl

CH

3 0 3-CH 3 , 5-CN H 3-chloro-

CH

2

CF

3 2-pyridinyl

CH

2

CH

3 0 3-CH 3 , 5-Cl 2-chlorophenyl H

CH

3

CH

2

CH

3 0 3-Br, 5-Cl 2-chlorophenyl H

CH

3

CH

2

CH

3 0 3-Br, 5-Br 2-chlorophenyl H

CH

3

CH

2

CH

3 0 3-CH 3 , 5-CN 2-chlorophenyl H

CH

3

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro- H

CH

3 2-pyridinyl

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro- H

CH

3 2-pyridinyl

CH

2

CH

3 0 3-Br, 5-Br 3-chloro- H

CH

3 2-pyridinyl

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro- H

CH

3 2-pyridinyl

CH

2

CH

3 0 3-CH 3 , 5-Cl H 2-chlorophenyl

CH

3

CH

2

CH

3 0 3-Br, 5-Cl H 2-chlorophenyl

CH

3

CH

2

CH

3 0 3-Br, 5-Br H 2-chlorophenyl

CH

3

CH

2

CH

3 0 3-CH 3 , 5-CN H 2-chlorophenyl

CH

3

CH

2

CH

3 0 3-CH 3 , 5-Cl H 3-chloro-

CH

3 2-pyridinyl

CH

2

CH

3 0 3-Br, 5-Cl H 3-chloro-

CH

3 2-pyridinyl

CH

2

CH

3 0 3-Br, 5-Br H 3-chloro-

CH

3 2-pyridinyl

CH

2

CH

3 0 3-CH 3 , 5-CN H 3-chloro-

CH

3 2-pyridinyl ,280 Table 88 Rb Ajz (R4)n Rienz-i R 14D~1R

CH

2 CH3 0 3-CH 3 , 5-Cl 2-chlorophenyl H C (CH3) 3

CH

2

CH

3 0 3-Br, 5-Cl 2-chlorophenyl H

C(CH

3

)

3

CH

2

CH

3 0 3.-Br, 5-Br 2-chlorophenyl H C (CH 3 ) 3

CH

2

CH

3 0 3-CH 3 , 5-CN 2-chlorophenyl H C (CH 3 ) 3

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro- H C (CH 3 )-3 2-pyridinyl

CH

2

CH

3 0 3-Br, 5-Cl 31-chloro- H

C(CH

3

)

3 2-pyridinyl

CH

2

CH

3 0 3-Br, 5-Br 3-chlioro- H

C(CH

3

)

3 2-pyridinyl

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro- H

C(CH

3

)

3 2-pyridinyl

CH

2

CH

3 0 3-CH 3 , 5-Cl H 2-chlorophenyl C (CH 3 ) 3

CH

2

CH

3 0 3-Br, 5-Cl H 2-chlorophenyl C (CH 3 ) 3

CH

2

CH

3 0 3-Br, 5-Br H 2-chlorophenyl

C(CH

3

)

3

CH

2

CH

3 0 3-CH 3 , 5-CN H 2-chlorophenyl

C(CH

3

)

3

CH

2

CH

3 0 3-CH 3 , 5-Cl H 3-chloro-

C(CH

3

)

3 2-pyridinyl

CH

2

CH

3 0 3-Br, 5-Cl H 3-chloro-

C(CH

3

)

3 __ 2-pyridinyl

CH

2

CH

3 0 3-Br, 5-Br H 3-chloro- C (CH 3 ) 3 .__2-pyridinyl

CH

2

CH

3 0 3-CH 3 , 5-CN H 3-chloro- C(CH 3

)

3 2-pyridinyl

CH

2

CH

3 0 3-CH 3 , 5-Cl 2-chlorophenyl H

CH

2

CF

3

CH

2

CH

3 0 3-Br, 5-Cl 2-chlorophenyl H

CH

2

CF

3

CH

2

CH

3 0 3-Br, 5-Br 2-chlorophenyl H

CH

2

CF

3

CH

2

CH

3 0 3-CH 3 , 5-CN 2-chlorophenyl H

CH

2

CF

3

CH

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro- H

CH

2

CF

3 2-pyridinyl

CH

2

CH

3 0 3-Br, 5-Cl 3-chloro- H

CH

2

CF

3 2-pyridinyl

CH

2

CH

3 0 3-Br, 5-Br 3-chloro- H

CH

2

CF

3 2-pyridinyl

CH

2

CH

3 0 3-CH 3 , 5-CN 3-chloro- H

CH

2

CF

3 2-pyridinyl

CH

2

CH

3 0 3-CH 3 , 5-Cl H 2-chlorophenyl CH 2

CF

3

CH

2 CH3 0 3-Br, 5-Cl H 2-chlorophenyl CH 2

CF

3

CH

2

CH

3 0 3-Br, 5-Br H 2-chlorophenyl CH 2

CF

3

CH

2

CH

3 0 3-CH 3 , 5-CN H 2-chlorophenyl CH 2

CF

3

CH

2

CH

3 0 3-CH 3 , 5-Cl H 3-chloro-

CH

2

CF

3 2-pyridinyl

CH

2

CH

3 0 3-Br, 5-Cl H 3-chloro- CH 2

CF

3 2 -pyridinyl

CH

2

CH

3 0 3-Br, 5-Br H 3-chloro- CH 2

CF

3 2-pyridinyl

CH

2

CH

3 0 3-CH 3 , 5-CN H 3-chloro-

CH

2

CF

3 2-pyridinyl ,281 Table 89 Rb Az (R 4 )n Ri 4 bZ-1 ±iby-R

CH

3 0 3-CH 3 , 5-Cl 2-chlorophenyl H

CHF

2

CH

3 0 3-Br, 5-Cl 2-chlorophen 1 H

CHF

2

CH

3 0 3-Br, 5-Br 2-chlorophenyl H

CHF

2

CH

3 0 3-CH 3 , 5-CN 2-chlorophenyl H

CHF

2

CH

3 0 3-CH 3 , 5-Cl 3-chloro- H

CHF

2 2-pyridinyl

CH

3 0 3-Br, 5-Cl 3-chloro- H

CHF

2 2-pyridinyl CH3 0 3-Br, 5-Br 3-chloro- H

CHF

2 2-pyridinyl CH3 0 3-CH 3 , 5-CN 3-chloro- H

CHF

2 2-pyridinyl

CH

3 0 3-CH 3 , 5-Cl H 2-chlorophenyl CHF 2 CH3 0 3-Br, 5-Cl H 2-chlorophenyl CHF 2

CH

3 0 3-Br, 5-Br H 2-chlorophenyl CHF 2

CH

3 0 3-CH 3 , 5-CN H 2-chlorophenyl CHF 2 CH3 0 3-CH 3 , 5-Cl H 3-chloro- CHF 2 2-pyridinyl CH3 0 3-Br, 5-Cl H 3-chloro-

CHF

2 2-pyridinyl

CH

3 0 3-Br, 5-Br H 3-chloro-

CHF

2 2-pyridinyl CH3 0 3-CH 3 , 5-CN H 3-chloro- CHF 2 2-pyridinyl CH3 0 3-CH 3 , 5-Cl 2-chlorophenyl H CBrF 2

CH

3 0 3-Br, 5-Cl 2-chlorophenyl H CBrF 2

CH

3 0 3-Br, 5-Br 2-chlorophenyl H CBrF 2

CH

3 0 3-CH3, 5-CN 2-chlorophenyl H CBrF 2 CH3 0 3-CH3, 5-Cl 3-chloro- H CBrF 2 2-pyridinyl CH3 0 3-Br, 5-Cl 3-chloro- H CBrF 2 2-pyridinyl CH3 0 3-Br, 5-Br 3-chloro- H CBrF 2 2-pyridinyl CH3 0 3-CH3, 5-CN 3-chloro- H CBrF 2 2-pyridinyl CH3 0 3-CH3, 5-Cl H 2-chlorophenyl CBrF 2 CH3 0 3-Br, 5-Cl H 2-chlorophenyl CBrF 2 CH3 0 3-Br, 5-Br H 2-chlorophenyl CBrF 2 CH3 0 3-CH3, 5-CN H 2-chlorophenyl CBrF 2 CH3 0 3-CH 3 , 5-Cl H 3-chloro- CBrF 2 2-pyridinyl CH3 0 3-Br, 5-Cl H 3-chloro- CBrF 2 2-pyridinyl 013 0 3-Br, 5-Br H 3-chloro- CBrF 2 2-pyridinyl H3 0 3-CH3, 5-CN H 3-chloro- CBrF 2 2-pyridinyl .282 Examples of the pests against which the present compound has controlling efficacy include harmful arthropods such as harmful insects and harmful mites, and nemathelminths such as, 5 nematodes, and specific examples -are as shown below. Hemiptera: Planthoppers (Delphacidae) such as small brown planthopper (Laodelphax striatellus), brown rice planthopper (Nlaparvata lugens), and white-backed rice planthopper 10 (Sogatella furcfera); leafhoppers (Deltocephalidae) such as green, rice leafhopper (Nephotettix cincticeps), green rice leafhopper (Nephotettix virescens), and tea green leafhopper (Empoasca onukii); aphids (Aphididae) such as cotton aphid (Aphs gossypi2), green peach aphid (Myzus persicae), cabbage 15 aphid (Brevicoryne brassicae), spiraea aphid (Aphis spiraecola), potato aphid (Macrosiphum euphorblae), foxglove aphid (Aulacorthum solani), oat bird-cherry aphid (Rhopaloslphum padi), tropical citrus aphid (Toxoptera citricidus), and mealy plum aphid (Hyalopterus pruni); stink 20 bugs (Pentatomidae) such as green stink bug (Nezara antennata), bean bug (Rlptortus clavetus), rice bug (Leptocorisa chinenss), white spotted spined bug (Eysarcoris parvus), and stink bug (Halyomorpha mista); whiteflies (Aleyrodidae) such as greenhouse whitefly (Trialeurodes vaporarorum), 25 sweetpotato whitefly (Bemisia tabaci), silver leaf whitefly .283 (Bemisia argentifol1), citrus whitefly (Dzaleurodes catr2), and citrus spiny white fly (Aleurocanthus spaniferus); scales (Coccidae) such as Calfornia red scale (Aonidiella aurant::), San Jose scale (Comstockaspis perniciosa), citrus north scale' 5 (Unaspis c2tr2), red wax scale (Ceroplastes rubens), cottonycushion scale (Icerya purchase), Japanese mealybug (Planococcus kraunh~ae), Cosmstock mealybug (Pseudococcus longxispinis), and white peach scale (Pseudaulacaspis pentagona); lace bags (Tingidae); psyllids (Psyllidae); etc. 10 Lepidoptera: ,Pyralid moths (Pyralidae) such as rice stem borer (Chilo suppressalis), yellow rice borer (Tryporyza incertulas), rice leafroller (Cnaphalocrocis medinalis), cotton leafroller (Notarcha derogata) , Indian meal moth (Plodia interpunctella) , 15 oriental corn borer (Ostrzn2a furnacalis), cabbage webworm (Hellula undalas), and bluegrass webworm (Pediasia teterrellus); owlet moths (N6ctuidae) such as common cutworm (Spodoptera litura), beet armyworm (Spodoptera exigua), armyworm (Pseudaletia separata),cabbage armyworm (Mamestra 20 brassicae), black cutworm (Agrotas 2psilon), beet semi-looper (Plusia nagrasagna), Thoricoplusia spp., Heliothis spp., and Helacoverpa spp.; whites and sulfer butterflies (Pieridae) such as common white (Pieris rapae); tortricid moths (Tortricidae) such as Adoxophyes spp., oriental fruit moth 25 (Grapholata molesta), soybean pod borer (Leguminvora ,284 , glycznivorella), azuki bean podworm (Matsumuraeses azukivora), summer fruit tortrix (Adoxophyes orana fasciata), Adoxophyes sp., oriental tea tortrix (Homona magnanima), apple tortrix (Arch ps fuscocupreanus), and Cydia pomonella; leafblotch 5 miners (Gracillariidae) such as tea leafroller (Calopt2laa theivora), and apple leafminer (Phyllonorycter ringoneella); Carposinidae such as peach fruit moth (Carposina niponensls); lyonetiid moths (Lyonetiidae) such as Lyonetia spp.; tussock moths (Lymantriidae) such as Lymantria spp., and Euproctis 10 spp.; yponomeutid moths (Yponomeutidae) such as diamondback (Plutella xylostella); gelechild moths (Gelechiidae) such as pink bollworm (Pectinophora gossyp2ella), and potato tubeworm (Phthorimaea operculella); tiger moths and allies (Arctiidae) such as fall webworm (Hyphantr2a cunea); tineid moths 15 (Tineidae) such as casemaking clothes moth (Tinea translucens), and webbing clothes moth (T~neola blsselliella); etc. Thysanoptera: Thrips (Thripidae) such as yellow citrus thrips (Franklinzella occaidentals), Thrips parmi, yellow tea thraps 20 (Sc2rtothrsps dorsalis), onion thrip (Thrips tabaci), flower thrips (Franklinaella intonsa), etc. Diptera: Housefly (Musca domestica), common mosquito (Culex popaens pallens), horsefly (Tabanus trigonus), onion maggot 25 (Hylemya antiqua), seedcorn maggot (Hylemya platura), 285 Anopheles sinensis, rice leafminer (Agromyza oryzae) , rice leafminer (Hydrellia graseola), rice stem maggot (Chlorops oryzae), melon fly (Dacus cucurbatae), Ceratitzs capitata, legume leafminer (Lirzomyza trifola), tomato leafminer 5 (Larzomyza sativae), garden pea leafminer (Chromatomyia horticola), etc. Coleoptera: Twenty-eight-spotted ladybird (Epilachna viginti octopunctata), cucurbit leaf beetle (Aulacophora 10 femoralis), striped flea beetle (Phyllotreta striolata), rice leaf beetle (Oulema oryzae) , rice curculio (Echinocnemus squameus) , rice water weevil (Lassorhoptrus oryzophlus), Anthonomus grandis, azuki bean weevil (Callosobruchus chinensas) , Sphenophorus venatus, Japanese beetle (Popillia 15 Japonca), cupreous chafer (Anomala cuprea), corn root worm (Diabrotica spp.), Colorado beetle (Leptanotarsa decemlnieata), click beetle ('Agriotes spp.), cigarette beetle (Lasioderma serricorne), varied carper beetle (Anthrenus verbasca) , red flour beetle (Tribola um castaneum) , powder post 20 beetle (Lyctus brunneus), white-spotted longicorn beetle (Anoplophora malasiaca) , pine shoot beetle (Tomacus panperda) , etc. Orthoptera: Asiatic locust (Locusta migratorza), African mole cricket 25 (Gryllotalpa africana), rice grasshopper (Oxya yezoensis), .286 rice grasshopper (Oxya 3aponica), etc. Hymenoptera: Cabbage sawfly (Athalia rosae), Acromyrmex spp., fire ant (Solenopss spp.), etc. 5 Nematodes: Rice white-tip nematode (Aphelencho.des besseyi), strawberry bud nematode (Nothotylenchus acris), southern root-knot nematode (Meloidogyne incognita), northern root-knot nematode (Meloidogyne hapla), Javanese root-knot 10 nematode (Meloidogyne _7avanica), soybean cyst nematode (Heterodera glycines), potato cyst nematode (Globodera rostochiensis), coffee root-lesion nematode (Pratylenchus coffeae), California root-lesion nematode (Pratylenchus neglectus), etc. 15 Dictyoptera: German cockroach (Blattella germanica), smokybrown cockroach (Periplaneta fuliginosa), American cockroach (Periplaneta americana), Periplaneta brunnea, oriental cockroach (Blatta orientalis), etc. 20 Acarina: Spider mites (Tetranychidae) such as two-spotted spider mite (Tetranychus urticae), Kanzawa spider mite (Tetranychus kanzawa), citrus red mite (Panonychus cztri), European red mite (Panonychus ulm2), and Oligonychus spp.; eriophyid mites 25 (Eriophyidae) such as pink citrus rust mite (Aculopspelekassa), 287 pink citrus rust mite (Phyllocoptruta citr2), tomato rust mite (Aculops lycopersici) , purple tea mite (Calacarus carinatus) , pink tea rust mite (Acaphylla theavagran) , and Eriophyes chibaensis; tarosonemid mites (Tarsonemidae) such as broad, 5 mite (Polyphagotarsonemus latus); false spider mites (Tenuipalpidae) such as Brev2palpus phoenicis; Tuckerellidae; ticks (Ixodidae) such as Haemaphysalis longicornis, Haemaphysal s flava, Dermacentor taiwanscus, Ixodes ovatus, Ixodes persulcatus, Boophilus macroplus, and Rhipicephalus 10 sanguineus; acarid mites (Acaridae) such as mold mite (Tyrophagusputrescentiae) , and Tyrophagus samils; house dust mites (Pyroglyphidae) such as Dermatophagoides farinae, and Dermatophagoides ptrenyssnus; cheyletide mites (Cheyletidae) such as Cheyletus eruditus, Cheyletus malaccenss, and 15 Cheyletus moorei; parasitoid mites (Dermanyssidae); etc. The pesticide of the present invention may be the present compound itself but, usually, the present compound is mixed with an inert carrier such as a solid carrier, a liquid carrier, a gaseous carrier and the like and, if necessary, a surfactant, 20 and other preparation additives are added to formulate into a composition or a preparation such as an emulsion, oil, powder, granules, a wettable preparation, a flowable preparation, microcapsules, an aerosol, a fumigant, poison bait, a resin preparation or the like. These compositions or preparations 25 usually contain 0.01 to 95% by weight of the present compound.

288 Examples of the solid carrier to be used include fine powders and granules such as clays (kaolin clay, diatomaceous earth, bentonite, fubasami clay, acid clay, etc.), synthetic 5 hydrous silicon oxide, talc, ceramic, other inorganic minerals (sericite, quartz, sulfur, active carbon, calcium carbonate, hydrated silica, etc.), chemical fertilizers (ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride, etc.) and the like. 10 Examples of the liquid carrier include water, alcohols (methanol, ethanol, isopropyl alcohol, butanol, hexanol, benzyl alcohol, ethylene glycol, propylene glycol, phenoxyethanol, etc.), ketones (acetone, methyl ethyl ketone, cyclohexanone, etc.), aromatic hydrocarbons (toluene, xylene, 15 ethylbenzene, dodecylbenzene, phenylxylylethane, methylnaphthalene, etc.), aliphatic hydrocarbons (hexane, cyclohexane, kerosene, gas oil, etc.), esters (ethyl acetate, butyl acetate, isopropyl myristate, ethyl oleate, diisopropyl adipate, diisobutyl adipate, propylene glycol monomethyl ether 20 acetate, etc.), nitriles (acetonitrile, isobutyronitrile, etc.), ethers (dilsopropyl ether, 1, 4-dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, diethylene glycol monomethyl ether, propylene glycol monomethyl ether, dipropylene glycol monomethyl ether, 25 3-methoxyl-3-methyl-l-butanol, etc.), acid amides ,289 (N,N-dimethylformamide, N, N-dimethylacetamide, etc.), halogenated hydrocarbons (dichloromethane, trichloroethane, carbon tetrachloride, etc.), sulfoxides (dimethyl sulfoxide, etc.), carbonic propylene and vegetable oils (soybean oil, 5 cottonseed oil, etc.). Examples of the gaseous carrier include fluorocarbon, butane gas, LPG (liquefied petroleum gas), dimethyl ether, and carbonic acid gas. Examples of the surfactant include nonionic surfactants 10 such as polyoxyethylene alkyl ether, polyoxyethylene alkyl aryl ether, polyethylene glycol fatty acid ester, and the like, and anionic surfactants such as alkyl sulfonate salts, alkylbenzene sulfonate salts and alkyl sulfate salts. Examples of other preparation additives include binders, 15 dispersing agents, coloring agents and stabilizers, specifically, casein, gelatin, sugars (starch, gum arabic, cellulose derivatives, alginic acid, etc.), lignin derivatives, bentonite, synthetic water-soluble polymers (polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acids, etc.), PAP 20 (acidic isopropyl phosphate), BHT (2,6-di-tert-butyl-4 methylphenol), and BHA(a mixture of 2-tert-butyl-4 methoxyphenol and 3-tert-butyl-4-methoxyphenol). The method of controlling a pest of the present invention is usually performed by applying the pesticide of the present 25 invention directly to a pest or to a place where a pest inhabits ,290 (plant, soil, in house, animal, etc.). When the pesticide of the present invention is used for controlling a pest in the agricultural field, an amount to be applied is usually 1 to 10, 000 g per 10, 000 m 2 in terms of the 5 amount of the present'compound. When the pesticide of the present invention is formulated into an emulsion, a wettable preparation, a flowable preparation or the like, usually, the agent is applied by diluting with water so that the active ingredient concentration becomes 0.01 to 10,000 ppm, and 10 granules, powder or the like are usually applied as they are. ,These preparations, or preparations diluted with water may be directly applied to a pest or to a plant such as a crop to be protected against a pest, or may be applied to soil of a cultivated land in order to control a pest inhabiting in the 15 soil. Alternatively, treatment may be performed for example, by winding a sheet-like or string-like-processed resin preparation on a crop, surrounding a crop with the resin preparation, or laying the resin preparation on soil about 20 roots of a crop. When the pesticide of the present invention is used for controlling a pest which inhabits in a house (e.g. fly, mosquito, cockroach, etc.), the amount to be applied is usually 0.01 to 1000 mg per 1 m 2 of treating area in terms of the amount of the 25 present compound in case of surface treatment, and is usually 291 0.01 to 500 mg per 1 m 3 of treating space in terms of the amount of the present of compound in case of spatial treatment. When the pesticide of the present invention is formulated into an emulsion, a wettable preparation, a flowable preparation or.the 5 like, usually, the agent is applied by diluting with water so that the active ingredient-concentration becomes 0.1 to 1000 ppm, and oil', an aerosol, a fumigant, poison bait or the like is applied as it is. The pesticide of the present invention may contain other 10 harmful arthropod controlling agents, acaricides, nematicides, fungicides, herbicides, plant growth regulators, synergists, fertilizers, soil conditioners, animal feeds, and the like. As the active ingredients of the aforementioned other harmful arthropod controlling agents, acaricides and/or 15 nematicides, for example, the following compounds can be mentioned. (1) Organic phosphorus compounds Acephate, aluminium phosphide, butathiofos, cadusafos, chlorethoxyfos, chlorfenvinphos, chlorpyrifos, 20 chlorpyrifos-methyl, cyanophos: CYAP, diazinon, DCIP (dichlorodiisopropyl ether), dichlofenthion: ECP, dichlorvos: DDVP, dimethoate, dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, etrimfos, fenthion: MPP, fenitrothion: MEP, fosthiazate, formothion, hydrogen phosphide, isofenphos, 25 isoxathion, malathion, mesulfenfos, methidathion:

DMTP,

.292 monocrotophos, naled: BRP, oxydeprofos:ESP, parathion, phosalone, phosmet: PMP, pirimiphos-methyl, pyridafenthion, quinalphos, phenthoate: PAP, profenofos, propaphos, prothiofos, pyraclorfos, salithion, sulprofos, tebupirimfos, 5 temephos, tetrachlorvinphos, terbufos, thiometon, trichlorphon:DEP, vamidothion, and the like. (2) Carbamate compounds Alanycarb, bendiocarb, benfuracarb, BPMC, carbaryl, carbofuran, carbosulfan, cloethocarb, ethiofencarb, 10 fenobucarb, fenothiocarb, fenoxycarb, furathiocarb, isopr ocarb:MIPC, metolcarb, methomyl, methiocarb, NAC, oxamyl, pirimicarb, propoxur: PHC, XMC, thiodicarb, xylylcarb, and the like. (3) Synthetic pyrethroid compounds 15 Acrinathrin, allethrin, benfluthrin, beta-cyfluthrin, bifenthrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, deltamethrin, esfenvalerate, ethofenprox, fenpropathrin, fenvalerate, flucythrinate, flufenoprox, flumethrin, fluvalinate, halfenprox, imiprothrin, permethrin, 20 prallethrin, pyrethrins, resmethrin, sigma-cypermethrin, silafluofen, tefluthrin, tralomethrin, transfluthrin, 2,3,5, 6-tetrafluoro-4-(methoxymethyl)benzyl (EZ)-(lRS, 3RS;1RS,3SR)-2,2-dimethyl-3-prop-1-enylcyclopropanecarboxyl ate, 2,3,5,6-tetrafluoro-4-methylbenzyl 25 (EZ)-(lRS,3RS;1RS,3SR)-2,2-dimethyl-3-prop-1-enylcyclopropa .293 necarboxylate, 2,3,5,6-tetrafluoro- 4 -(methoxymethyl)benzyl (lRS, 3RS; 1RS, 3SR) -2, 2-dimethyl-3- (2-methyl-1-propenyl) cyclo propanecarboxylate, and the like. (4) Nereistoxin compounds 5 Cartap, bensultap, thiocyclam, monosultap, bisultap, and the like. (5) Neonicotinoid compounds Imidacloprid, nitenpyram, acetamiprid, thiamethoxam, thiacloprid, dinotefuran, clothianidin, and the like. 10 (6) Benzoylurea compounds ,Chlorfluazuron, bistrifluron, diafenthiuron, diflubenzuron, fluazuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron, triflumuron, and the like. 15 (7) Phenylpyrazole compounds Acetoprole, ethiprole, fipronil, vaniliprole, pyriprole, pyrafluprole, and the like. (8) Bt toxin insecticides Viable endospores derived from Bacillus thuringiensis and 20 crystalline toxins produced by it, as well as a mixture of thereof. (9) Hydrazine compounds Chromafenozide, halofenozide, methoxyfenozide, tebufenozide, and the like. 25 (10) Organic chlorine compounds 294 Aldrin, dieldrin, dienochlor, endosulfan, methoxychlor, and the like. (11) Natural insecticides Machine oil, nicotine-sulfate, and the like. 5 (12) Other insecticides Avermectin-B, bromopropylate, buprofezin, chlorphenapyr, cyromazine, 1, 3-Dichloropropene, emamectin-benzoate, fenazaquin, flupyrazofos, hydroprene, indoxacarb, metoxadiazone, milbemycin-A, pymetrozine, pyridalyl, 10 pyriproxyfen, spinosad, sulfluramid, tolfenpyrad, triazamate, flubendiamide, SI-0009, cyflumetofen, arsenic acid, benclothiaz, calcium cyanamide, calcium polysulfide, chlordane, DDT, DSP, flufenerim, flonicamid, flurimfen, formetanate, metam-ammonium, metam-sodium, Methyl bromide, 15 nidinotefuran, Potassium oleate, protrifenbute, spiromesifen, sulfur, metaflumizone, spirotetramat, and the like. Acaricides Acequinocyl, amitraz, benzoximate, bromopropylate, chinomethionat, chlorobenzilate, CPCBS (chlorfenson), 20 clofentezine, Kelthane(dicofol), etoxazole, fenbutatin oxide, fenothiocarb, fenpyroximate, fluacrypyrim, fluproxyfen, hexythiazox, propargite:BPPS, polynactins, pyridaben, Pyrimidifen, tebufenpyrad, tetradifon, spirodiclofen, amidoflumet, Bifenazate, Cyflumetofen, and the like. 25 Nematicides (nematicidal active ingredients) 295 DCIP, fosthiazate, levamisol, methyisothiocya,nate, morantel tartarate, and the like. The present invention will be explained in more detail 5 below by way of Preparation Examples, Formulation Examples, Test Examples, but the present invention is not limited to. these Examples. First, Preparation Examples of the present compound will be explained. 10 Preparation Example 1 ,A mixture of 0.22 g of N-(2-aminobenzoyl)-N' ethoxycarbonylhydrazine, 0.31 g of 1-(3-chloro-2-pyridinyl) 3-trifluoromethyl-1H-pyrazole-5-carbonyl chloride and 10 ml of pyridine was stirred at room temperature for 2 hours. Water 15 was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0. 13 g of the present compound (1) of the 'formula:

F

3 0 0 C N H N H N OCH 2

CH

3 (1) CI O NN'r H 0 The present compound (1) 20 'H-NMR(CDCl3,TMS)5(ppm):1.35(3H,t,J=8Hz),4.29(2H,q,J=8Hz), 6.85(lH,brs),7.10(lH,t,J=8Hz),7.24(lH,s),7.44(lH,t,J=8Hz), 7.47(1H,dd,J=8Hz,4Hz),7.62(lH,d,J=8Hz),7.93(lH,d,J= 4 Hz), 296 8.42(1H,brs),8.46(lH,d,J=8Hz),8.52(lH,d,J=8Hz),11.

8 6 (1H, brs) Preparation Example 2 A mixture of 0.213 g of 1-methyl-lH-pyrrole-2-carbox-ylib 5 acid, 0.15 g of thionyl chloride and 5 ml of hexane was heated under reflux for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 0.14 g of 1-methyl-1H pyrrole-2-carbonyl chloride. To a mixture of 0.22 g of N-(2-aminobenzoyl)-N'-ethoxycarbonylhydrazine and 10 ml of 10 pyridine was added 0.14 g of the resulting 1-methyl-1H-pyrrole 2-carbonyl chloride, and the mixture was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.11 g of the present compound (2) of the 15 formula: 0 N' - H H(2 N OCH 2

CH

3

CH

3 0 N H 0 The present compound (2) H-NMR(DMSO-d6 ,TMS)6(ppm):1.02-1.28(3H,m), 3

.

9 1( 3 H,s), 4.00-4.16(2H,m),6.13(lH,d,J=4Hz),6.78(1H,d,J=4Hz), 7 .06 20 (lH,m),7.15(H,t,J=8Hz),7.56(1H,t,J=8Hz),7.79(1H,d,J=8Hz), 8.57(1H,d,J=8Hz),9.30(1H,brs),10.57(1H,brs),11.63(1H,brs) Preparation Example 3 297 A mixture of 0.19 g of 1-methyl-3-trifluoromethyl 1H-pyrazole-5-carboxylic acid, 0.15 g of thionyl chloride and 5 ml of hexane was heated under reflux for 2 hours. The reaction mixture was concentrated under reduced pressure to obtain 0.14 5 g of 1-methyl-3-trifluoromethyl-1H-pyrazole-5-carbonyl chloride. To a mixture of 0.22 g of N-(2-aminobenzoyl)-N' ethoxycarbonylhydrazine and 10 ml of pyridine was added 0.14 g of the resulting 1-methyl-3-trifluoromethyl-lH-pyrazole 5-carbonyl chloride and the mixture was stirred at room 10 temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitates were collected by filtration to obtain 0.23 g of the present compound (3) of the formula:

F

3 C 0 N N H (3) I H ,N OCH 2

CH

3

CH

3 0 N H 0 15 The present compound (3) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):1.20(3H,t,J=8Hz), 4 .10( 2 H,q, J=8Hz),4.19(3H,s),7.17(1H,s),7.28(1H,t,J=8Hz),7.60(lH,t, J=8Hz),7.79(lH,d,J=8Hz),8.37(lH,d,J=8Hz),9.02(1H,brs),10.41 (1H,brs),11.50(1H,brs) 20 Preparation Example 4 Amixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl- ,298 1H-pyrazole-5-carboxamide, 0.06 g of ethyl chloroformate and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.08 g of.the 5 present compound (4) of the formula:

F

3 C H 3 C CI 0 N N H N H -N OCH 2

CH

3 C N H The present compound (4) H-NMR(DMSO-d6,TMS)(ppm):0.96-1.26( 3 H,m), 2 .16( 3 H,s), 3

.

9 0- 4 .1 2

(

2 H,m),7.38(lH,s),7.55(1H,s),7.66(lH,dd,J=8Hz, 4 Hz) 10 ,7.71(lH,s),8.22(l1H,d,J=8Hz),8.53(1H,d,J=4Hz),9.25(lH,brs), 10.14(lH,brs),10.37(lH,brs) Preparation Example 5 A mixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl] -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 15 1H-pyrazole-5-carboxamide, 0.05 g of methyl chloroformate and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0. 16 g of the present compound (5) of the formula: ,299

H

3 C CI F3 0 H 'N H H (5)

-

N OCH3 H 0 The present compound (5) H-NMR(DMSO-d,TMS)(ppm):2.16(3H,s),3.62(3H,s), 7

.

39 (lH,s), 7.56(1H,s),7.67(1H,dd,J=8Hz,4Hz),7.70(1H,s),8.22(lH,d, 5 J=8Hz),8.54(1H,d,J=4Hz),9.31(1H,brs),10.17(lH,brs),10.38 (1H,brs) Preparation Example 6 A mixture of 0.22 g of N- [4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl] -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 10 1H-pyrazole-5-carboxamide, 0.05 g of isopropyl chloroformate and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.21 g of the present compound (6) of the formula: H3C CI

F

3 C H0 c N N H H -N OCH(CH 3

)

2 Ci 0 N N H O 15 The present compound (6) 'H-NMR(DMSO-d 6 ,TMS)(ppm):0.97-1.31(6H,m), 2 .1 6

(

3 H,s), . 300 4

.

6 8

-

4 .89(1H,m),7.38(1H,S),7.55(1H,S),7.66(lH,dd,J=8Hz, 4 Hz),7.71(1H,S),8.22(1H,d,J=8Hz),8.53(lH,d,J=4Hz), 9 .1 8 (1H, brs),10.12(lH,brs),10.37(lH,brs) Preparation Example 7 5 A mixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl) -1- (3-chloro-2-pyridinyl) -3-trif luoromethyl 1H-pyrazole-5-carboxamide, 0.05 g of cyclopropanecarbonyl chloride and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and 10 a deposited precipitate was collected by filtration to obtain 0.20,g of the present compound (7) of the formula: F H 3 C C1 F3C O0 N, N H(7 'N HH-N C N 0 N N H 0 The present compound (7) H-NMR(DMSO-d 6 ,TMS)6(ppm):0.57-0.82(4H,m),1.

63 -1.

73 (lH,m), 15 2.16(3H,s),7.43(1H,s),7.54(lH,s),7.66(1H,dd,J=8Hz,4Hz),7.74 (lH,s),8.22(lH,d,J=BHz),8.53(lH,d,J=4Hz),10.1 9

(

2 H,brs), 10.40 (lH,brs) Preparation Example 8 Amixture of 0.22 g of N- (4 -chloro-2-(hydrazinocarbonyl) 20 6-methylphenyl) -1- (3-chloro-2-pyridinyl ) -3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0.07 g of benzoyl chloride and 10 ,301 ml of pyridine was stirred at room temperature for, 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.15 g of the present compound (8) of the formula:

H

3 C Ci F3C 0 N N H (8) N H C N 0 N'Y N H6 5 The present compound (8) rH-.NMR(DMSOdr,TMS)(ppm):2.8(3H,s),7.48-7.69(5H,m), 7

.

77 (lH,s),7.90-7.96(3H,m),8.22(1-H,d,J=8Hz),8.55(lH,d,J=4Hz), 10.36(lH,brs),10.42(lH,brs),10.60(lH,brs) 10 Preparation Example 9 A mixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0.07 g of 4-morpholinecarbonyl chloride and 10 ml of pyridine was stirred at room temperature 15 for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.12 g of the present compound (9) of the formula: 302 H3C CI

F

3 C O0 / N N H (9) H N N C I N O N' T ""N , H The present compound (9) H-NMR(DMSO-d 6 ,TMS)5(ppm):2.15(3H,s), 3

.

22

-

3

.

42

(

4 Hm), 3 .53- 3 .63(4H,m),,7.44(1H,s),7.53(lH,s),7.66(1H,dd,J=8Hz, 5 4Hz),7.77(1H,s),8.22(1H,d,J=8Hz),8.54(1H,d,J=4Hz),8.78(lH, brs),9.88(1H,brs),10.33(1H,brs) Preparation Example 10 A mixture of 0.22 g of N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro 10 2-pyridinyl) -3-trifluoromethyl-1H-pyrazole-5-carboxamide, 0.06 g of N,N-dimethylcarbamoyl chloride and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0. 13 g of the present compound 15 (10) of the formula:

H

3 C CI F3C 0 N, N H (0 N H Y ,,N N(CH3)2 C1 O N' r N H O The present compound (10) 303 H-NMR(DMSO-d 6 ,TMS)(ppm):2.14(3H,s),2.86(6H,s),7.

42 (1H,s), 7.52(1H,s),7.67(1H,dd,J=8Hz,4Hz),7.82(lH,s),8.22 (lH,d,J=8Hz),8.48-8.58(2H,m),9.83(1H,brs),10.

3 1(1H,brs) Preparation Example 11 5 A mixture of 0.22 giof N-[4-chloro-2- (hydrazinocarbonyl) 6-methylphenyl] -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0.06 g of N-propyl chloroformate and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited 10 precipitate was collected by filtration to obtain 0.24 g of the present compound (11) of the formula:

F

3 C H 3 C 3C 'N N H H -N OCH 2

CH

2

CH

3 CI 0 N Y N H 0 The present compound (11) 1H-NMR(DMSO-d6,TMS)(ppm):0.66-0.98(3H,m),1.

37 -1.6 6

(

2 H,m), 15 2.16(3H,s),3.83-4.08(2H,m),7.38(1H,s),7.55(1H,s),7.66(1H, dd,J=8Hz,4Hz),7.71(lH,s),8.22(1H,d,J=8Hz),8.5 3 (lH,d,J= 4 Hz), 9.26(lH,brs),10.14(1H,brs),10.37(lH,brs) Preparation Example 12 A mixture of 0.22 g of N-[4-chloro-2- (hydrazinocarbonyl) 20 6-methylphenyl) -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0.05 g of ethyl isocyanate and 10 ml of tetrahydrofuran was stirred at room temperature for 2 -304 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.16 g of the present compound (12) of the formula: H3C C1

F

3 C O0 N, N H H (12) N H N N CI 0 N' ' 'CH 2

CH

3 "N H 5 The present compound (12) 1H-NMR(DMSO-dG,TMS)(ppm):1.12(3H,t,J=6Hz),2.18( 3 H,s), 3

.

7 8 (2H,q,J=6Hz),6.34(1H,m),7.48(1H,s),7.54(1H,s),7.65-7.69(2H, m),7.74(1H,brs),8.23(1H,d,J=8Hz),8.54(1H,d,J= 4 Hz), 9

.

99 (lH, brs),10.34(lH,brs) 10 Preparation Example 13 Amixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0.07 g of phenyl isocyanate and 10 ml of tetrahydrofuran was stirred at room temperature for 2 15 hours. Water was poured into the reaction mixture, and a deposited precipitates were collected by filtration to obtain 0.12 g of the present compound (13) of the formula: 305

F

3 C

H

3 C Ci N'N N H H (13) 'N HO N N The present compound (13) H-NMR(DMSO-d6,dTMS)6(ppm):2.18(3H,s),6.9 3 -7.00( 2 Hm), 7

.

2 1 7.31(2H,m) ,7.40-7.47 (2H,m),7.51(1H, s),7.54-7.58 (1H,m),7.66 5 (1H,dd,J=BHz,4Hz),7.71(lH,s),8.22(1H,d,J=BHz),8.53(lH,d, J=4Hz),8.73(1H,brs),10.18(1H,brs),10.

40 (1H,brs) Preparation Example 14 A mixture of 0.24 g of N-(2-methylaminobenzoyl)-N' ethoxycarbonylhydrazine, 0.31 g of 1-(3-chloro-2 10 pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carbonyl chloride and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.20 g of the present compound (14) of the formula:

F

3 C 0 / N N 'N H (14) C1

CH

3 0 N'N OCH2CH3 N H 0 15 The present compound (14) 'H-NMR(DMSO-d ,TMS) 6 (ppm) :1.06-1.27 (3H,m) ,3.18 (3H, s) ,4.01 4 .16(2H,m),6.34(H,s),7.31-7.37(1H,m),7.53-7.61( 3 H,m), 7

.

71 ,306 (1H,dd,J=8Hz,4Hz) ,8.31 (1H,d,J=8Hz) ,8.62 (lH,d,J=4Hz) ,9.33 (lH,brs),10.44(1H,brs) Preparation Example 15 A mixture of 0.22 g of N- (4-chloro-2- (hydrazinocarbonyl) 5 6-methylphenyl) -1- (3-chloro-2-pyridinyl) -3-trif luoromethyl 1H-pyrazole-5-carboxamide, 0.05 g of ethanesulfonyl chloride and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.14 g of the 10 present compound (15) of the formula:

H

3 C CI

F

3 C 0 / 'N N HO (15) Ni 00' C NH O CH2CH3 The present compound (15) 1H-NMR(DMSO-d 6 ,TMS)5(ppm):1.20(3H,t,J=8Hz), 2

.

18

(

3 H,s), 3 .02 (2H,q,J=8Hz),7.39(lH,s),7.57(1H,s),7.66(1H,dd,J=8Hz,4Hz), 15 7.68(1H,s),8.22(1H,d,J=8Hz),8.53(1H,d,J=4Hz),9.95(1H,brs), 10.41(1H,brs),10.57(1H,brs) Preparation Example 16 Amixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 20 1H-pyrazole-5-carboxamide, 0.05 g of N,N-dimethylsulfamoyl chloride and 10 ml of pyridine was stirred at room temperature .307 for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.14 g of the present compound (16) of the forrpula: H3C CI

F

3 C 0 N'N N HO (16) 0 H C1 N O N, N(CH3)2 5 The present compound (16) .H-NMR(DMSO-d 6 ,TMS)(ppm):2.16(3H,s),2.71(6H,s), 7

.

28 (lH,s), 7.57 (1H,s),7.66(1H,dd,J=8Hz,4Hz),7.75(lH,s),8.2 2 (lH,d, J=8Hz),8.53(lH,d,J=4Hz), 9.31(.lH,brs),10.42 (1H,brs),10.51 (lH,brs) 10 Preparation Example 17 A mixture of 0.22 g of N-[I4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 1H-pyrazole-5-carboxamide, 10 mL of formi6 acid and 5 ml of acetic anhydride prepared under ice-cooling was stirred at room 15 temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.02 g of the present compound (17) of the formula: .308

F

3 C H 3 C Ci 0 - ' F3NNH (17) H NH N H0

H'N

0 C1IL N ,H O The present compound (17) 1H-NMR(DMSO-d6,TMS)6(ppm):2.16(3H,s),7.43(lH,s), 7 .56(lH,s), 7.66(1H,dd,J=8Hz,4Hz),7.73(1H,s),8.05(1H,s),8.

22 (lH,d, 5 J=8Hz),8.53(1H,d,J=4Hz),10.13(1H,brs),10.39(1H,brs),10.4 6 (1H,brs) Preparation Example 18 A mixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 10 1H-pyrazole-5-carboxamide, 0.05 g of propionyl chloride and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0. 15 g of the present compound (18) of the formula: F H 3 C C1 F3CN N0(8 N H~ N H 'H N CH 2

CH

3 N H 0 15 The present compound (18) H-NMR(DMSO-d 6 ,TMS)6(ppm):1.04(3H,t,J=8Hz),2.13(5H,m),7.44 ,309 (1H,s),7.55(1H,S),7.66(lH,dd,J=8HZ,4HZ),7.74(1H,s),8.

22 (1H, d,J=8Hz),8.54(1H,d,J=4Hz),9.91(1H,brs),10.16(1H,brs),10.

36 (1H,brs) Preparation Example 19 5 A mixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyll -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0.05 g of n-butyl chloroformate and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited 10 precipitate was collected by filtration to obtain 0.19 g of the present compound (19) of the formula: H3C C1

F

3 C O0 / N' N N H (19) NH H N OCH 2

CH

2

CH

2

CH

3 CI 0 N r N H 0 The present compound (19) H-NMR(DMSO-d6,TMS)5(ppm):0.79-0.94(3H,m),1.

22 -1.40( 2 H,m), 15 1.46-1.62(2H,m),2.17(3H,s),3.92-4.13(2H,m),7.37(1H,s),7.56 (lH,s),7.66(1H,dd,J=8Hz,4Hz),7.70(lH,s),8.22(1H,d,J=BHz), 8.53 (1H,d,J=4Hz) , 9.25 (1H,brs),10.14 (lH,brs),10.37 (lH,brs) Preparation Example 20 A mixture of 0.22 g of N-[4-chloro-2- (hydrazinocarbonyl) 20 6-methylphenyl) -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0.05 g of allyl chloroformate and 310 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.23 g of the present compound (20) of the formula:

F

3 C H 3 C CI 0 F3N N H (20) Hi0 -N OCH2CH=CH2 N H 0 5 The present compound (20) 'H-NMR(DMSO-d 6 ,TMS)5(ppm) :2.16(3H,s),4.43-4.60(2H,m),5.21 (lH,d,J=6Hz) ,5.33 (lH,d,J=8Hz),5.86-6.00 (1H,m) , 7

.

39 (lH,s) , 7.56(1H,s),7.66(1H,dd,J=BHz,4Hz),7.70(1H,s), 8

.

22 (1H,d, 10 J=8Hz) ,8.54 (1H, d, J=4Hz) 9.39(1H,brs),10.18 (1H,brs),10.38 (lH,brs) Preparation Example 21 A mixture of 0.22 g of N-[4-chloro-2-(N methylhydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro-2 15 pyridinyl)-3-trifluoromethyl-lH-pyrazole-5-carboxamide, 0. 05 g of methyl chloroformate and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction solution, and a deposited precipitate was collected by filtration to obtain 0.09 g of the present compound (21) of 20 the formula: ,311

F

3 C

H

3 C CI 0

-

F3C N H N H N

OCH

3 Cl .0

CH

3 O The present compound (21) 1H-NMR(DMSO-d 6 ,TMS)5(ppm):2.11(3H,s),3.0 6

(

3 H,s), 3

.

3 3

(

3 H,s), 7.07(1H,s),7.45(lH,s),7.68(lH,s),7.69(1H,dd,J=BHz,4Hz),8.24 5 (1H,d,J=8Hz),8.55(1H,d,J=4Hz),9.11(0.6H,brs),10.20(1H,brs), 10.54 (0.4H,brs) Preparation Example 22 Amixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl] -1- (3-chloro-2.-pyridinyl) -3-trifluoromethyl 10 1H-pyrazole-5-carboxamide, 0.05 g of N,N-diethylcarbamoyl chloride and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.19 g of the present compound (22) of the formula:

F

3 C H 3 C C1 0 / N'N N H (22) N H -N

N(CH

2

CH

3

)

2 N H 0 15 The present compound (22) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):1.06(6H,t,J=6Hz),2.14(3H,s),3.26 (4H,q,J=6Hz),7.42(lH,s),7.52(1H,s),7.68(1H,dd,J=8Hz, 4 Hz), 7.82(1H,s),8.23(1H,d,J=8Hz),8.48(1H,brs),8.53(1H,d,J=4Hz), 312 9.84(lH,brs),10.35(lH,brs) Preparation Example 23 Amixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 5 1H-pyrazole-5-carboxamide, 0.10 g of N-methyl-N phenylcarbamoyl chloride and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.19 g of the present compound (23) of a 10 formula:

H

3 C C1

F

3 C 'N N H CH 3 (23) HI . N N- C10 N Y }f yz C 1 N H The present compound (23) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.15(3H,s),3.08( 3 H,s), 7 .10- 7

.

4 5 (6H,m),7.53(1H,s),7.66(1H,dd,J=8Hz,4Hz),7.76(1H,s),8.

14 15 (1H,brs),8.20(1H,d,J=8Hz),8.50(1H,d,J=4Hz),9.97(1H,brs), 10.32(lH,brs) Preparation Example 24 Amixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 20 1H-pyrazole-5-carboxamide, 0.15 g of N,N-diphenylcarbamoyl chloride and 10 ml of pyridine was stirred at room temperature .313 for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.24 g of the present compound (24) of the formula: F H3C CI

F

3 C O NN H H 1 , (24) CI N HO NN N H 0 5 The present compound (24) 1H-NMR(DMSO-d6 ,TMS)5(ppm):2.15(3H,s),6.77(lH,t,J=8Hz),6.81 (lH,t,,J=8Hz),7.05-7.39(9H,m),7.52(lH,s),7.6 4 (lH,dd,J=8Hz, 4Hz),7.72(lH,s), 8.13(H,brs),,8.19(1H,d,J=BHz)8.47(1H,d, J=4Hz),10.08(lH,brs),10.34(lH,brs) 10 Preparation Example 25 Amixture of 0.22 g of N- [4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl) -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0.07 g of picolinoyl chloride hydrochloride and 10 ml of pyridine was stirred at room 15 temperature for 2 hours. Water was poured into a reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.16 g of the present compound (25) of the formula: -314 H3C 'Cl

F

3 C 0 / N N H H (25) CI O NN N "N H O The present compound (25) H-NMR(DMSO-d 6 ,TMS)6(ppm):2.18(3H,s), 7 .50- 7

.

59

(

2 H,m), 7.63-7.71(3H,m).,7.77-7.88 (1H,m),8.05(1H, s),8.06(1H, s), 8.23 5 (lH,d,J=8Hz),8.54(H,d,J=4Hz),8.70(lH,d,J=4Hz),10.

35 -10.

7 0 (2H,m) Preparation Example 26 A mixture of 0.22 g of N-[4-chloro-2- (hydrazinocarbonyl) 6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 10 1H-pyrazole-5-carboxamide, 0.07 g of phenyl chloroformate and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.16 g of the present compound (26) of a formula:

F

3 C 83C CI N' NN H 'N H N 0 (26) C0 N O N O 15 The present compound (26) 'H-NMR(DMSO-d6,TMS)6(ppm):2.17(3H,s),7.1 3

-

7

.

69

(

9 H,m), 8

.

22 (lH,d,J=8Hz)8.53(lH,d,J=4Hz),9.95(1H,brs),10.

43 (lH,brs), .315 10.45 (1H,brs) Preparation Example 27 A mixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl]-1- (3-chloro-2-pyridinyl)-3-trifluoromethyl 2 5 1H-pyrazole-5-carboxamide, 0.04 g of acetyl chloride and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0. 22 g of the present compound (27) of the formula:

H

3 C

F

3 C / C N'N N H ,(27) YH N NCH3 C N O N' N H 0 10 The present compound (27) 'H-NMR(DMSO-dr>,TMS)5(ppm):1.89(3H,s),2.16(3H,s),7.44(1H,s), 7

.

5 5(1H,s),7.66(lH,dd,J=8Hz,4Hz),7.73(lH,s),8.

21

(

1 H,d, J=8Hz),8.54(lH,d,J=4Hz),9.94(lH,brs),10.17(lH,brs),10.38 15 (1H,brs) Preparation Example 28 Amixture of 0.22 g of N-[4-chloro-2-(hydra zinocarbonyl) 6-methylphenyl] -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0.06 g of trimethylacetyl chloride 20 and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited .316 precipitate was collected by filtration to obtain 0.25 g of the present compound (28) of the formula: H3C C1

F

3 C O 0i N- N H ,(28) H -N

C(CH

3

)

3 H 0 The present compound (28) 5 1H-NMR(DMSO-d6 ,TMS)6(ppm):1.17(9H,s),2.15(3H,s),7.46(1H,s), 7

.

5 4(1H,s),7.66(1H,dd,J=8Hz,4Hz),7.76(1H,s),8.2 3 (lH,d, J=8Hz),8.54(lH,d,J=4Hz),9.66(1H,brs),10.01(lH,brs),10.

32 (lH,brs) Preparation Example 29 10 A mixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl] -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0.05 g of methyl chlorothiol formate of the formula: CI

SCH

3 0 15 and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 0.10 g of the present compound (29) of the formula: 317

F

3 C H 3 C C1 0 N, N H (29) H .N SCH 3 C0, N' r C N H o The present compound (29) 1H-NMR(DMSO-'dTMS)6(ppm):2.03-2.34(6H,m),7.40(lH,s), 7 .58 (lH,s),7.66(lH,dd,J=8Hz,4Hz),7.71(lH,s),8.22(lH,d,J=BHz), 5 8.53(lH,d,J=4Hz),9.84(lH,brs),10.41(lH,brs),10.

56 (lHbrs) Preparation Example 30 A mixture of 0.22 g of N-[4-chloro-2- (hydrazinocarbonyl) 6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0.09 g of 3-methylbenzoyl chloride 10 and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filteration to obtain 0.19 g of the present compound (30) of'the formula:

H

3 C C1

F

3 C 0

CH

3 N,N N H (30) N HN Cl O N "'N 0 N' 6 N H 0 15 The present compound (30) H-NMR(DMSO-d 6 ,TMS)5(ppm):2.18(3H,s),2.30( 3 H,s), 7

.

4 0(lH,s), 7 .55(lH,s),7.58(lH,s),7.65-7.73(4H,m),7.77(1H,s),8.

23 (lH, 318 d,J=8Hz),8.54(1H,d,J=4Hz),10.35(lH,brs),10.41(lH,brs),10.

54 (1H,brs) Preparation Example 31 A mixture of 0.22 g of N-[4-chloro-2-(hydrazinocarbonyl) 5 6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 1H-pyrazole-5-carboxamide,' 0.09 g of 4-methoxybenzoyl chloride and 10 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 10 0.09 g of the present compound (31) of the formula: H3C Cl

F

3 C 0 /

OCH

3 H, N (31) CI ' O N' N H HO The present compound (31) 1H-NMR(DMSO-dsTMS)5(ppm):2.18(3H,s),3.83(3H,s), 7 .04( 2 H,d, J=8Hz),7.55 (lH, s),7.58 (1H, s),7.69 (1H,dd, J=8Hz, 4Hz),7.77 (lH, 15 s),7.90(2H,d,8Hz),8.23(lH,d,J=8Hz),8.54(lH,d,J=4Hz),10.28 (lH,brs),10.41(lH,brs),10.45(lH,brs) Preparation Examples 32 A mixture of 0.18 g of 1-(3-chloro-2-pyridinyl) N-[2- (hydrazinocarbonyl) -6-methylphenyl] -3-trifluoromethyl 20 1H-pyrazole-5-carboxamide, 0.06 ml of ethyl chloroformate and 1 ml of pyridine was stirred at room temperature for 2 hours.

.319 Water and toluene were added successively to the reaction mixture, and the mixture was concentrated under reduced pressure. The resulting residue was mixed with methyl tert-butyl ether and water, the mixture was separated into 5 layers, the resulting organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.14 g of the present compound (32) 10 of the formula:

H

3 C

F

3 C 0 H N OCH 2

CH

3 (32) N H O The present compound (32) 'H-NMR(CDCl 3 ,TMS)5(ppm):1.26(3H,brm),2.21( 3 H,s), 4 .1 8

(

2 H, brq,J=7Hz),6.88(1H,brs),7.17(lH,t,J=8Hz),7.28-7.39(4H,m), 15 7.86(lH,d,J=8Hz),8.05(lH,brs),8.43(lH,d,J=4Hz),9.73(lH,brs) Preparation Example 33 A mixture of 0.21 g of N-[2-chloro-6-(hydrazinocarbonyl)pheny1]-1-(3-chloro-2 pyridinyl) -3-trifluoromethyl-1H-pyrazole-5-carboxamide, 20 0.06 ml of ethyl chloroformate and 5 ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the 320 reaction mixture, and the mixture was extracted with methyl tert-butyl ether three times. The organic layers were combined, washed successively with 2 mol/L-hydrochloric ac.d, an aqueous saturated sodium bicarbonate solution and an aqueous saturated 5 sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.16 g of the present compound (33) of the formula: CI

F

3 0 0 N 'N N H (33) N H 'N H ' N OCH 2

C

3 (3 j'N H 0 10 The present compound (33) H-NMR(CDCl3,TMS)56(ppm):1.28(3H,t,J=7Hz),4.21(2H,q,J=7Hz), 6 .76(lH,brs),7.23-7.30(2H,m),7.42(lH,dd,J=8Hz,4Hz), 7 .50(1H, d,J=8Hz),7.55(1H,d,J=8Hz),7.85(lH,brs),7.90(lH,dd,J=BHz, 15 lHz),8.47(lH,dd,J=4Hz,1Hz),9.16(1H,brs) Preparation Example 34 A mixture of 0.30 g of 3-bromo-N-[4-chloro- 2 -(hydrazinocarbonyl) -6-methylphenyl] 1- (3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide, 0.20 ml 20 of methyl chloroformate, 0.09 ml of triethylamine, 20 ml of acetonitrile and 10 ml of N,N-dimethylformamide was stirred at .321 room temperature for 3 hours. Water was poured into the reaction mixture, and the mixture was extracted with methyl tert-butyl ether three times. The organic layers yere combined, washed with an aqueous saturated sodium chloride solution, 5 dried with anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0. 13 g of the present compound (34) of the formula: I Br H 3 C CI 0 / HH N H NH CH (34) HN OCH3 C1 N' NH O 10 The present compound (34) 'H-NMR(DMSO-d 6 )5(ppm):2.14(3H,s),3.61(3H,brs), 7

.

33 (lH,s), 7.37(lH,brs),7.53(lH,brs),7.60(lH,dd,J=8Hz,4Hz),8.16(lH,dd, J=8Hz,1Hz),8.49(lH,dd,J=4Hz,1Hz),9.29(lH,brs),10.15(lH, brs) ,10.22 (1H,brs) 15 Preparation Example 35 A mixture of 0.30g of 3-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2 pyridinyl)-1H-pyrazole-5-carboxamide, 0.09ml of ethyl chloroformate and 3ml of pyridine was stirred at room 20 temperature for 3 hours, and concentrated under reduced pressure. Water and toluene were added to the resulting residue, 322 the mixture was filtered, the resulting filter cake was mixed with methyl tert-butyl ether and water, and the mixture was separated into layers. The organic layer was washed with an aqueous saturated sodium chloride solution, dried over 5 anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.23g of the present compound (35) of the formula:

H

3 C CI Br O N, N H (35) H N OCH 2

CH

3 (35) CN O N ci0

N'

0 C '1N H O 10 The present compound (35) 1H-NMR(DMSO-d6)6(ppm):1.18(3H,brm),2.14(3H,s),4.06(2H,brm), 7.34(lH,s),7.37(lH,brs),7.53(lH,s),7.60(lH,dd,J=8Hz,4Hz), 8.16(lH,dd,J=8Hz,1Hz),8.49(lH,dd,J=4Hz,lHz),9.24(lH,brs), 10.12(1H,brs),10.21(1H,brs) 15 Preparation Examples 36 and 37 To a solution of 0.30g of N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (2-chlorophenyl) -3 trifluoromethyl-lH-pyrazole-5-carboxamide in 10ml of acetonitrile were added 0.10ml of methyl chloroformate and 20 0.09ml of triethylamine, the mixture was stirred at room temperature for 1 hour, and 0.10 ml of methyl chloroformate was 323 added to the mixture, followed by further stirring for 3 hours. Water was poured into the reaction mixture, and the mixture was extracted with methyl tert-butyl ether three times. The organic layers were combined, washed with an aqueous saturated 5 sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0. 16g of the present compound (36) and 0.16g of the present compound (37) of the fromulas: H3C C1

F

3 C 0 / N' N O (36) 'N H __ ) -OCH 3 CI N-N 10 ~H 0 OCH3 10 The present compound (36) 1H-NMR(CDCl 3 ,TMS)5(ppm):2.15(3H,s),3.76(6H,s),7.

23

-

7

.

27

(

3 H, m),7.30-7.40(2H,m),7.43-7.47(2H,m),8.84(lH,brs), 9

.

29 (lH, brs) H3C Cl

F

3 C 0 3 3CN N H (37) 'N H N

OCH

3 0 N1 CI O ' 0 15 The present compound (37) H-NMR(DMSO-d 6 )5(ppm):2.22(3H,s),3.68(3H,brs),7.44(lH,brs), 7.53-7-72(6H,m),9.35(lH,brs),10.23(lH,brs),10.32(lH,brs) 324 Preparation Example 38 A mixture of 0.30g of N-[4-chloro-2- (hydrazinocarbonyl) 6-methylphenyl] -1- (2-chlorophenyl) -3-trifluoromethyl-lH pyrazole-5-carboxamide, 2ml of pyridine and 0.09ml of ethyl' 5 chloroformate was stirred at room temperature for 1 hour, and concentrated under reduced pressure. Water and toluene were added to the resulting residue, and the mixture was filtered. The filter cake was subjected to silica gel column chromatography to obtain 0.22g of the present compound (38) or 10 the formula:

H

3 C C1

F

3 C O / N N H (38) H .N

OCH

2

CH

3 H 0 The present compound (38) 1 H-NMR(DMSO-dr>)5(ppm):1.19(3H,brm),2.15(3H,s),4.05(2H,brm), 7.37(1H,s),7.49-7.66(6H,m),9.22(1H,brs),10.14(1H,brs),10.25 15 (1H,brs) Preparation Example 39 A mixture of 0.18g of 1-(3-chloro-2-pyridinyl)-N [2-(hydrazinocarbonyl)-6-methylphenyl)-3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0. 05ml of methyl chloroformate and 20 1ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and toluene was ,325 added, followed by concentration under reduced pressure. The resulting residue was mixed with methyl tert-butyl ether and water, the mixture was separated into layers, and the organic layer was washed with an aqueous saturated sodium chloride 5 solution, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.13g of the present compound (39) of the formula: H3C

F

3 C O0 / 'N H H (39) N ,N CH

H

0 6 10 The present compound (39) H-NMR (CDC 3 , TMS) 6 (ppm) :2.22 (3H, s) , 3. 75 (3H, brs) , 6.

86 (lH, brs),7.19(lH,t,J=8Hz),7.27(lH,s),7.34-7.40(3H,m), 7

.

87 (lH, dd,J=8Hz,1.5Hz),7.97(lH,brs);8.44(lH,J=4Hz,1Hz),9.68(lH, brs) 15 Preparation Example 40 A mixture of 0.30g of N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2 pyridinyl)-1H-pyrazole-5-carboxamide, 0.09ml of methyl chloroformate and 3 ml of pyridine was stirred at room 20 temperature for 1.5 hours. Water and toluene were successively added to the reaction mixture, followed by concentration under .326 reduced pressure. The resulting residue was mixed with ethyl acetate and water, the mixture was separated into layers, and the organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and 5 concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.20g of the present compound (40) of the formula:

H

3 C CI 0 /1 N7 N H (40) N H .. N

OCH

3 N H 0 The present compound (40) 10 H-NMR(DMSO-d)(ppm):2.17(3H,s),3.62(3H,brs), 7

.

2 5 (lH,d, J=2Hz),7.40(lH,brs),7.52(lH,d,J=2Hz),7.56(lH,dd,J=8Hz,4Hz), 7

.

86 (lH,d,J=2Hz),8.11(lH,dd,J=8Hz,lHz),8.48(lH,dd,J= 4 Hz, lHz),9.31(lH,brs),10.ll(lH,brs),10.13(1H,brs) Preparation Example 41 15 According to the same manner as that of Preparation Example 5, N- [4, 6-dimethyl-2- (hydrazinocarbonyl)phenyl] 1- (3-chloro-2-pyridinyl) -3-trifluoromethyl-lH-pyrazole-5 carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro-2 20 pyridinyl)-3-trifluoromethyl-lH-pyrazole-5-carboxamide to obtain the present compound (41) of the formula: .327

H

3 C

CH

3 F3C 0 NN H (41) 'N H N

OCH

3 C1 N N' N H 6 The present compound (41) H-NMR(DMSO-d,TMS)6(ppm):2.11(3H,s),2.29(3H,s), 3 .55- 3 .68 (3H,m),7.19-7.25(2H,m),7.66(lH,dd,J=8Hz,4Hz),7.71(lH,s), 5 8.22(1H,d,J=8Hz),8.53(lH,d,J=4Hz),9.23(1H,brs),9.98(1H, brs) ,10.22(1H,brs) Preparation Example 42 According to the same manner as that of Preparation Example 10, N- [4, 6-dimethyl-2- (hydrazinocarbonyl)phenyl] 10 1- (3-chloro-2-pyridinyl) -3-trifluoromethyl-1H-pyrazole-5 carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl) -6-methylpheny] -1- (3-chloro-2 pyridinyl) -3-trifluorlmethyl-1H-pyrazole-5-carboxamide to obtain the present compound (42) of the formula:

F

3 C H 3 C CH 3 N N H (42) H N N(CH 3

)

2 CI O N " N H 6 15 The present compound (42) 'H-NMR(DMSO-dsTMS)5(ppm):2.13(3H,s),2.31( 3 H,s), 2 .8 6

(

6 Hs), ,328 7. 14-7.27 (2H,m),7. 65-7.70 (1H,m),7 .82 (1H, s),8.23 (1H,d, J=8Hz),8.48(1H,brs),8.53(1H,d,J=4Hz),9.65(1H,brs),10.1 6 (lH, brs) Preparation Example 43 5 According to the same manner as that of Preparation Example 5, N- [6-bromo-2- (hydrazinocarbonyl) -4-methylphenyl) 1- (3-chloro-2-pyridinyl) -3-trifluoromethyl-lH-pyrazole-5 carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2 10 pyridinyl)-3-trifluoromethyl-lH-pyrazole-5-carboxamide to obtain the present compound (43) of the formula: Br CH

F

3 C O 3 N NH (43) N H H N OCH 3 CI ON N H O The present compound (43) H-NMR(DMSO-de ,dTMS)5(ppm):2.35(3H,s),3.53-3.65(3Hm), 7 .35 15 (lH, s),7.65(lH,dd,J=8Hz, 4Hz),7.68-7.70 (1H,m),7.76(lH, s), 8.

2 0(1H,d,J=8Hz),8.53(1H,d,J=4Hz),9.27(1lH,brs),10.04(lH, brs) ,10.47 (1H,brs) Preparation Example 44 According to the same manner as that of Preparation 20 Example 10, N-[6-bromo-2-(hydrazinocarbonyl)-4 methylphenyl) -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl- 329 1H-pyrazole-5-carboxamide was used in place of N-[4-chloro 2-(hydrazinocarbonyl)-6-methylpheny]-1-(3-chloro-2 pyridinyl)-3-trifluorlmethyl-1H-pyrazole-5-carboxamide to obtain the present compound (44) of the formula:

F

3 C Br CH 3 N N H (44) H ,N N(CH3)2

H

0 N 1N H O 5 The present compound (44) IH-NMR(DMSO-d 6 ,TMS)5(ppm):2.34 (3H,s),2.84 (6H,s),7.40 (lH,s), 7 .62-7.70(2H,m),7.83(lH,s),8.20(lH,d,J=8Hz),8.48(lH,brs), 8.51-8.56(lH,m),9.69(lH,brs),10.42(lH,brs) 10 Preparation Example 45 According to the same manner as that of Preparation Example 5, N-[3-chloro-2-(hydrazinocarbonyl)phenyl]-1-( 3 chloro-2-pyridinyl)-3-triflubromethyl-lH-pyrazole-5 carboxamide was used in place of N-[4-chloro-2 15 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2 pyridinyl)-3-trifluoromethyl-lH-pyrazole-5-carboxamide to obtain the present compound (45) of the formula:

F

3 C 0 ' F3C AN CI (45) 'N H .NH

OCH

3 C0 0 N N H 0 .330 The present compound (45) 'H-NMR(DMSO-d6,TMS)6(ppm):3.67-3.74(3H,m),7.37-7.4 7

(

2 Hm), 7

.

69

-

7

.

7 4 (lH,m),7.82-7.88(2H,m),8.25-8.33(1H,m),8.5 7 (lH,d, J=4Hz) ,9.71 (lH,brs) ,9.83 (1H,brs) ,10.56 (lH,brs) 5 Preparation Example 46 According to the same manner as that of Preparation Example 10, 'N-[4-chloro-2-(hydrazinocarbonyl)phenyl]-l-( 3 chloro-2-pyridinyl) -3-trifluoromethyl-1H-pyrazole-5-carboxa mide was used in place of N-[4-chloro-2-(hydrazinocarbonyl) 10 6-methylpheny] -1- (3-chloro-2-pyridinyl) -3-trifluorlmethyl 1H-pyrazole-5-carboxamide to obtain the present compound (46) of the formula:

F

3 C 0 C1 N'N N H (46) 'N H .,-N

N(CH

3

)

2 CI0 N , y N H o The present compound (46) 15 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.90(6H,),7.57(H,d,J=8Hz), 7 .68 7

.

70 (.lH,m),7.73(lH,dd,8Hz,4Hz),7.8 (1RH,s),8.18(1H,d,J=8Hz), 8.

2 9 (1H,d,J=8Hz),8.57(1H,d,J=4Hz),8.83(lH,brs),10.

3 6(lH, brs) , 11. 27 (1H, brs) Preparation Example 47 20 According to the same manner as that of Preparation Example 5, N-[4-chloro-2-(hydrazinocarbonyl)phenyl)-1-( 3 chloro-2-pyridinyl) -3-trifluoromethyl-H-pyrazole-5- .331 carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2 pyridinyl) -3-trifluoromethyl-1H-pyrazole-5-carboxamide to obtain the present compound (47) of the formula:

F

3 C O CI N H H (47) H N OCH3 Cl 0 N H O 5 The present compound (47) 1H-NMR(DMSO-dsTMS)(ppm):3.64-3.71(3H,m),7.5 9 (1H,s), 7 .63 (lH,d,J=8Hz) ,7.72(1H,dd,J=8Hz,4Hz) ,7.86(1H,s), 8

.

1 2 (lH,d, J=8Hz),8.29(1H,d,J=8Hz),8.58(1H,d,J=4Hz),9.51(1H,brs),10.

75 10 (1H,brs),11.68(1H,brs) Preparation Example 48 A mixture of 0.22g of N-[4-chloro-2- (hydrazinocarbonyl) 6-methylphenyl] -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 1H-pyrazole-5-carboxamide, 0.04g of sodium cyanate, 0.5ml of 15 acetic acid and 5ml of chloroform was stirred under ice-cooling for 4 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was washed successively with water and chloroform to obtain 0.080g of the present compound (48) of the formula: 332

F

3 C

H

3 C CI 0 1:" N HH (48) %N H -. ,N NH2 C I OL N NZ H The present compound (48) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.16(3H,s),5.97(2H,brs), 7 .5 2

-

7 .54 (2H,m) ,7. 67 (1H,dd, J=8Hz, 4Hz) , 7.70 (1H,s) ,7.76 (1H,brs) ,8.22 5 (lH,d,J=8Hz),8.,54(1H,d,J=4Hz),10.01(1H,brs),10.

39 (lH,brs) Preparation Example 49 According to the same manner as that of Preparation Example 5 except that N-[4,6-dibromo-2 (hydrazinocarbonyl)phenyl] -1- (3-chloro-2-pyridinyl) -3 10 trifluoromethyl-1H-pyrazole-5-carboxamide was used in place of N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl) -1 (3-chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazole-5 carboxamide to obtain the present compound (49) of the formula:

F

3 C Br Br N H (49) N H .N OCH 3 C0 N N H 0 15 The present compound (49) H-NMR(DMSO-d,TMS)5(ppm):3.40-3.70(3H,m),7.63- 7 .6 9

(

2 H,m), 7

.

7 6 (lH,s),8.16(lH,s),8.21(1H,d,J=8Hz),8.54(1H,d,J= 4 Hz), 9.35(1H,brs),10.23(1H,brs),10.63(lH,brs) Preparation Example 50 333 According to the same manner as that of Preparation Example 5 except that N-[4,6-diiodo-2 (hydrazinocarbonyl)phenyl] -1- (3-chloro-2-pyridinyl) -3 trifluoromethyl-1H-pyrazole-5-carboxamide was used in place 5 of N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl]-l-(3 chloro-2-pyridinyl)-3-trifluoromethyl-lH-pyrazole-5 carboxamide to obtain the present compound (50) of the formula:

F

3 C o N N H (50) %N H -N. OCH3 CI N H The present compound (50) 10 'H-NMR(DMSO-d 6 ,TMS)5(ppm):3.55-3.65(3H,m),7.65(lH,dd,J=8Hz, 4Hz),7.75-7.82(2H,m),8.20(lH,d,J=8Hz),8.39(lH,s),8.53(1H,d, J=4Hz),9.31(lH,brs),10.14(lH,brs),10.59(lH,brs) Preparation Example 51 A mixture of 0.22g of N-[4-chloro-2 15 (hydrazinocarbonyl)-6-methylphenyl)-1-(3-chloro-2 pyridinyl)-3-trifluoromethyl-lH-pyrazole-5-carboxamide, 0.05g of methyl isothiocyanate and 10ml of tetrahydrofuran was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected 20 by filtration to obtain 0.20g of the present compound (51) of the formula: 334

F

3 C H 3 C C 0 N H H (51) H N NHCH3 C1 N 0 N N H S The present compound (51) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.20(3H,s),2.85(3H,d,J=4Hz),7.5 7 (1H,s),7.60-'7.63(2H,m),7.68(1H,dd,J=8Hz,4Hz),7.72(1H,brs), 5 8.24(1H,d,J=8Hz),8.57(1H,d,J=4Hz),9.13(lH,brs),10.31(1H, brs) ,10.42(1H,brs) Preparation Example 52 According to the same manner as that of Preparation Example 5 except that N-[5-chloro-2 10 (hydrazinocarbonyl)phenyl]-1- (3-chloro-2-pyridinyl) -3 trifluoromethyl-1H-pyrazole-5-carboxamide was used in place of N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl]-1-(3 chloro-2-pyridinyl) -3-trifluoromethyl-1H-pyrazole-5 carboxamide to obtain the present compound (52) of the formula: C1 F 3 C 0 : FNCN N H (52) H -N

OCH

3 C N O N N H 0 15 The present compound (52) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):3.60-3.77(3H,m),7.40(1H,d,J=8Hz), 7.57(1H,s),7.74(1H,dd,J=8Hz,4Hz),7.85(1,d,J=8Hz),8.22(1H, ,335 s),8.31(1H,d,J=8Hz),8.59(1H,d,J=4Hz),9.49(1H,brs),10.

77 (lH, brs) ,12.04 (1H,brs) Preparation Example 53 According to the same manner as that of Preparation 5 Example 5 except that N-[2-(hydrazinocarbonyl)-4 methylphenyl]-1-(3-chloro-'2-pyridinyl)-3-trifluoromethyl 1H-pyrazole-5-carboxamide was used in place of N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl]-1-(3 chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazole-5 10 carboxamide to obtain the present compound (53) of the formula:

F

3 CN N CH 3 N H H (3 .H .N OCH 3 C N 0 N H O The present compound (53) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.32(3H,s),3.60-3.72(3H,m), 7

.

37 (1H,d,J=BHz),7.55(1H,s),7.65(lH,s),7.73(1H,dd,J=8Hz,4Hz), 15 8.02(1H,d,J=8Hz),8.29(1H,d,J=8Hz),8.57(1H,d,J=4Hz),9.43(1H, brs),10.64(1H,brs),11.72(1H,brs) Preparation Example 54 According to the same manner as that of Preparation Example 10 except that N-[2-(hydrazinocarbonyl) 20 4-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl -1H-pyrazole-5-carboxamide was used in place of N- [4-chloro-2 (hydrazinocarbonyl)-6-methylpheny]-1-(3-chloro-2- , 336 pyridinyl)-3-trifluorlmethyl-1H-pyrazole-5-carboxamide to obtain the present compound (54) of the formula:

F

3 C 0 . H F3C N HH (54) N H -N

N(CH

3

)

2 CI ON N N H The present compound (54) 5 1 H-NMR(DMSO-d 6 ,TMS)5(ppm):2.31(3H,s),2.91(6H,s),7.29- 7

.

34 (1H,m),7.48-7.51(1H,m),7.70-7.79(2H,m),8.04-8.09(1H,m),8.

26 -8.33(1H,m),8.55-8.60(1H,m),8.75(lH,brs),10.24(lH,brs), 11. 30,(1H,brs) Preparation Example 55 10 According to the same manner as that of Preparation Example 5 except that N-[2-(hydrazinocarbonyl) 3-methylphenyl) -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 1H-pyrazole-5-carboxamide was used in place of N-[4-chloro 2-(hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2 15 pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carboxamide to obtain the present compound (55) of the formula:

F

3 C 0 / NH' N CH3 (55) 'N H .1.,NH OCH3 C N 0 N' N H O The present compound (55) 'H-NMR(DMSO-d 6 ,TMS) 5(ppm):2.32(3H,s),3.62-3.75(3H,m), 7 .1 2 -337 (1H,d,J=8Hz),7.31(lH,t,J=8Hz),7.61(lH,d,J=8Hz),7.

68

-

7

.

73 (1H,m),7.80(1H,s),8.27(lH,d,J=8Hz),8.56(lH,d,J=4Hz), 9

.

59 (1H,brs),9.66(1H,brs),10.30(1H,brs) Preparation Example 56 5 According to the same manner as that of Preparation Example 5 except that N-[4,6-dichloro-2 (hydrazinocarbonyl) phenyl] -1- (3-chloro-2-pyridinyl) -3 trifluoromethyl-1H-pyrazole-5-carboxamide was used in place of N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl]-1-(3 10 chloro-2-pyridinyl) -3-trifluoromethyl-1H-pyrazole-5 carboxamide to obtain the present compound (56) of the formula: C1 C1

F

3 C O N N H (56) H -N OCH 3 0I NN 0 N H 0 The present compound (56) 1 H-NMR(DMSO-d 6 ,TMS)5(ppm):3.45-3.66(3H,m), 7 .51(lH,s), 7

.

66 15 (1H,dd,J=8Hz,4Hz),7.76(lH,s),7.94(lH,s),8.21(1H,d,J= 8 Hz), 8.53(1H,d,J=4Hz),9.37(1H,brs),10.27(1H,brs),10.64(1H,brs) Preparation Example 57 According to the same manner as that of Preparation Example 10 except that N-[4,6-dichloro-2 20 (hydrazinocarbonyl)phenyl]-1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-1H-pyrazole-5-carboxamide was used in place of N-[4-chloro-2-(hydrazinocarbonyl)-6-methylpheny]-l-(3- 338 chloro-2-pyridinyl) -3-trifluorlmethyl-lH-pyrazole-5 carboxamide to obtain the present compound (57) of the formula: CI Ci

F

3 C 0 _ N N H (57) H -N N(CH 3

)

2 0 N 1N H The present compound (57) 5 'H-NMR(DMSO-d 6 ,TMS)6(ppm):2.85(6H,s),7.58(lH,s),7.64-7.70 (1H,m),7.85(lH,s),7.90(1H,s),8.22(lH,d,J=8Hz),8.54(lH,d, J=4Hz),8.58(lH,brs),9.91(1H,brs),10.59(lH,brs) Preparation Example 58 According to the same manner as that of Preparation 10 Example 10 except that N-(4,6-dibromo-2 (hydrazinocarbonyl)phenyl]-l- (3-chloro-2-pyridiny1)-3 trifluoromethyl-1H-pyrazole-5-carboxamide was used in place of N-[4-chloro-2-(hydrazinocarbonyl)-6-methylpheny]-l-(3 chloro-2-pyridinyl)-3-trifluorlmethyl-lH-pyrazole-5 15 carboxamide to obtain the present compound (58) of the formula:

F

3 C Br Br N7 N H (58) H -..N

N(CH

3

)

2 1 N 0 N H O The present compound (58) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.84(6H,s),7.67(1H,dd,J=8Hz,4Hz), 7.74(1H,s),7.83(lH,s),8.13(1H,s),8.21(1H,d,J=8Hz),8.52-8.57 339 (2H,m) ,9.88 (lH,brs) ,10.60 (lH,brs) Preparation Example 59 According to the same manner as that of Preparation Example 5 except that N-[6-bromo-4-chloro-2 5 (hydrazinocarbonyl)phenyl]-1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-lH-pyrazole-5-carboxamide was used in place of N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl) -1- (3 chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazole-5 carboxamide to obtain the present compound (59) of the formula:

F

3 C Br Ci N HH (59) 'N H H N yOCH3 C--1N H O 10 The present compound (59) 1H-NMR(DMSO-d,TMS)5(ppm):3.55-3.65(3H,m),7.54(lH,s),7.66 (lH,dd,J=8Hz,4Hz),7.76(lH,s),8.06(1H,s),8.21(1H,d,J= 8 Hz), 8 .53(1H,d,J=4Hz),9.36(lH,brs),10.23(1H,brs),10.

64 (lH,brs) 15 Preparation Example 60 According to the same manner as that of Preparation Example 10 except that N-[6-bromo-4-chloro-2 (hydrazinocarbonyl)phenyl]-1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-lH-pyrazole-5-carboxamide was used in place 20 of N-[4-chloro-2-(hydrazinocarbonyl)-6-methylpheny]-1-(3 chloro-2-pyridinyl)-3-trifluorlmethyl-lH-pyrazole-5 carboxamide to obtain the present compound (60) of the formula: .340 BrN.Cl

F

3 C B N/ N H (60) %N H H N N(CH 3

)

2 CI O N y H 0 The present compound (60) 'H-NMR(DMSO-d 6 ,TMS)6(ppm):2.84(6H,s),7.62(1H,s),7.67(1H,dd, J=8Hz,4Hz),7.83(1H,s),8.02(1H,s),8.21(1H,d,J=8Hz),8.52-8.5 7 5 (2H,m),9.87(1H,brs),10.60(1H,brs) Preparation Example 61 According to the same manner as that of Preparation Example 10 except that N-[4,6-diiodo-2 (hydrazinocarbonyl) phenyl] -1- (3-chloro-2-pyridinyl) -3 10 trifluoromethyl-1H-pyrazole-5-carboxamide was used in place of N-[4-chloro-2-(hydrazinocarbonyl)-6-methylpheny]-1-(3 chloro-2-pyridinyl)-3-trifluorlmethyl-1H-pyrazole-5 carboxamide to obtain the present compound (61) of the formula:

F

3 C 0 N/ N H (61) %N H H N N(CH 3

)

2 CI O N H O 15 The present compound (61) 1 H-NMR(DMSO-d 6 ,TMS)6(ppm):2.83(6H,s),7.66(1H,dd,J=8Hz,4Hz), 7.82(1H,s),7.88(1H,s),8.21(1H,d,J=8Hz),8.37(1H,s),8.48(1H, brs),8.53(1H,d,J=4Hz),9.78(1H,brs),10.55(1H,brs) Preparation Example 62 341 According to the same manner as that of Preparation Example 10 except that N-[5-chloro-2 (hydrazinocarbonyl) phenyl] -1- (3-chloro-2-pyridinyl) -3 trifluoromethyl-1H-pyrazole-5-carboxamide was used in place' 5 of N-[4-chloro-2-(hydrazinocarbonyl)-6-methylpheny]-1-(3 chloro-2-pyridinyl) -3-trif'luoromethyl-1H-pyrazole-5 carboxamide to obtain the present compound (62) of the formula: Cl F1C N H (62) 'N H -N

N(CH

3

)

2 CI O 0 N N H O The present compound (62) 10 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.91(6H,s),7.33-7.

4 8(lH,m), 7

.

67 7.81(3H,m),8.24-8.35(2H,m),8.56-8.63(lH,m),8.80(lH,brs), 10.38(1H,brs),11.57(lH,brs) Preparation Example 63 According to the same manner as that of Preparation 15 Example 5 except that N-[2-(hydrazinocarbonyl)-5 methyphenyl)-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H pyrazole-5-carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2 pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carboxamide to 20 obtain the present compound (63) of the formula: 342

CH

3

F

3 C O / N N H (63) Cl. N H N NyOCH3 C N 0 N N H O The present compound (63) 1H-NMR(DMSO-'d,,TMS)5(ppm):2.32(3H,s),3.60-3.69(3H,m), 7 .0 9 (1H,d,J=8Hz),7.,54(1H,s),7.71-7.79(2H,m),8.06(1H,s),8.30(lH, 5 d,J=8Hz),8.58(1H,d,J=4Hz),9.41(1H,brs),10.64(lH,brs),12.19 (1H,brs) Preparation Example 64 According to the same manner as that of Preparation Example 10 except that N-(2-(hydrazinocarbonyl)-5 10 methylphenyl) -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 1H-pyrazole-5-carboxamide was used in place of N-[4-chloro 2- (hydrazinocarbonyl) -6-methylpheny] -1- (3-chloro-2 pyridinyl)-3-trifluorlmethyl-1H-pyrazole-5-carboxamide to obtain the present compound (64) of the formula:

CH

3

F

3 C 0 FCN N H (64) H N

N(CH

3

)

2 Nl0 N N: H 0 15 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.31(3H,s),2.90(6H,s),7.07(1H,d, J=8Hz),7.64-7.68 (2H,m),7.74(1H,dd,J=8Hz,4Hz),8.07(1H,s), 343 8.31(lH,d,J=8Hz),8.58(lH,d,J=4Hz),8.67(lH,brs),10.28(1H, brs),11.82(lH,brs) Preparation Example 65 According to the same manner as that of Preparation 5 Example 3 except that N-(2-amino-5-chloro-3 methylbenzoyl)-N'-methoxycarbonylhydrazine was used in place of N-(2-aminobenzoyl)-N'-ethoxycarbonylhydrazine to obtain the present compound (65) of the formula:

F

3 C

H

3 C C1 N N H (65) H -".,N OCH3

CH

3 0 N Y H . 10 The present compound (65) 1 H-NMR(DMSO-d 6 ,TMS)6(ppm):2.25(3H,s),3.59(3H,s), 4 .1 3

(

3 H,s), 7.40(1H,s),7.44(lH,s),7.59(1H,s),9.26(lH,brs),10.11(lH, brs),10.17 (lH,brs) Preparation Example 66 15 A mixture of 0.28g of N-[1-chloro-3-(hydrazinocarbonyl) 2-naphthyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H pyrazole-5-carboxamide, 0.06g of methyl chloroformate and 10ml of pyridine was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited 20 precipitate was collected by filtration to obtain 0.08g of the present compound (66) of the formula: 344 Cl

F

3 C O / N NH (66) N H -. ,N OCH3 CI 0 N N ' H O I The present compound (66) IH-NMR(DMSO-d 6 ,TMS)6(ppm):3.60-3.68(3H,m),7.35-7.43(1H,m), 7.60-7.85(3H,m),8.12-8.28(3H,m),8.52-8.60(2H,m),9.35(1H, 5 brs),10.32(1H,brs),10.76(1H,brs) Preparation Example 67 ,According to the same manner as that of Preparation Example 66 except that N-[l-bromo-3-(hydrazinocarbonyl)-2 naphthyl)-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-lH 10 pyrazole-5-carboxamide was used in place of N-[1-chloro-3 (hydrazinocarbonyl)-2-naphthyl]-1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-lH-pyrazole-5-carboxamide to obtain the present compound (67) of the formula: Br

F

3 C N N H (67) C N, HO NN

OCH

3 C N 0iz N" N HY H 0 15 The present compound (67) 1 H-NMR(DMSO-d 6 ,TMS)5(ppm):3.58-3.69(3H,m),7.34-7.44(lH,m), 7.60-7.85(3H,m),8.l0-8.28(3H,m),8.50-8.62(2H,m),9.33(1H, 345 brs),10.28(1H,brs),10.78(lH,brs) Preparation Example 68 A mixture of 0.30g of 2-[3-bromo-l-(3-chloro-2 pyridinyl)-lH-pyrazole-5-yl]-6,8-dibromo-4H-3,1 5 benzoxazine-4-one, 0.45g of methyl carbazate and 10ml of N,N-dimethylformamide was stirred at room temperature for 10 hours. Int6 the reaction mixture, 30ml of water was poured, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed with an aqueous 10 saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.14g of the present compound (68) of the formula: Br Br Br N N H (68) H N OCH3 N H O 15 The present compound (68) 1H-NMR(DMSO-d 6 ,TMS)6(ppm):3.44-3.66(3H,m),7.45(lH,s), 7 .60 (lH,dd,J=8Hz,4Hz),7.65(lH,s),8.14-8.18(2H,m),8.50(1H,d, J=4Hz),9.36(lH,brs),10.26(lH,brs),10.55(lH,brs) 20 Preparation Example 69 According to the same manner as that of Preparation Example 5 except that N-[4-chloro-2-(hydrazinocarbonyl)-6- 346 methyphenyl) -1- (2-pyridinyl)-3-trifluoromethyl-lH-pyrazole 5-carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro-2 pyridinyl)-3-trifluoromethyl-lH-pyrazole-5-carboxamide to 5 obtain the present compound (69) of the formula:

F

3 C

H

3 C CI N /- N H (69) 'N H .- N

OCH

3 O N N H The present compound (69) 'H-NMR(DMSO-d 6 )5(ppm):2.33(3H,s),3.63(3H,s), 7

.

36

(

2 H,s), 7 .52 10 (lH,dd, J=8Hz, 4Hz) ,7.58(lH, s) ,7.81(lH,d, J=8Hz) ,8.06 (lH, t, J=8Hz),8.46(lH,d,J=4Hz),9.33(lH,brs),10.19(lH,brs),10.

34 (lH,brs) Preparation Example 70 A mixture of 0.30g of 2-[3-bromo-1-(3-chloro-2 15 pyridinyl)-1H-pyrazole-5-yl)-8-bromo-6-chloro-4H- 3 ,1 benzoxazine-4-one, 0.45g of methyl carbazate and 10ml of N,N-dimethylformamide was stirred at room temperature for 10 hours. Into the reaction mixture, 30ml of water was poured and the mixture was extracted with ethyl acetate three times. The 20 organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium .347 sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.13g of the present compound (70) of the formula: B Br C1 N N H (70) H Y -N

OCH

3 0 NY N H O 5 The present compound (70) H-NMR(DMSO-d6 ,TMS)5(ppm):3.48-3.62(3H,m),7.41(lH,s), 7 .53 7

.

62 (,2H,m),8.05(lH,s),8.16(lH,d,J=8Hz),8.50(lH,d,J=4Hz), 9.36(lH,brs),10.21(lH,brs),10.48(lH,brs) 10 Preparation Example 71 A mixture of 0.30g of 2-[3-bromo-1-(3-chloro-2 pyridinyl)-lH-pyrazole-5-yl]-8-bromo-6-methyl-4H-3,1 benzoxazine-4-one, 0.45g of methyl carbazate and 10ml of N,N-dimethylformamide was stirred at room temperature for 10 15 hours. Into the reaction mixture, 30ml of water was, poured, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. 20 The resulting residue was subjected to silica gel column chromatography to obtain 0.17g of the present compound (71) of the formula: 348 B Br

CH

3 N H (71) N ' H -N

OCH

3 Cl"' 0 N r N H 0 The present compound (71) 1 H-NMR(DMSO-d 6 ,TMS)5(ppm):2.34(3H,s),3.56-3.64(3H,m),7.32 7.44(2H,m),7.59(1H,dd,J=8Hz,4Hz),7.66-7.71(1H,m),8.15(lH,d, 5 J=8Hz),8.49(1H,d,J=4Hz),9.27(1H,brs),10.01(1H,brs),10.31 (1H,brs) Preparation Example 72 ,A mixture of 0.21g of 2-(3-bromo-l-(3-chloro-2 pyridinyl)-H-pyrazole-5-yl]-8-chloro-4H-3,1-benzoxazine- 4 10 one, 0. 9g of methyl carbazate and 10ml of N,N-dimethylformamide was stirred at room temperature for 10 hours. Water was poured into the reaction mixture, and this was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure. The 15 resulting residue was subjected to silica gel column chromatography to obtain 0.10g of the present compound (72) of the formula: CI BrO N N H (72) H -0N

OCH

3 C0 0 N y N H O The present compound (72) 4349 1 H-NMR(DMSO-d 6 ,TMS) 5(ppm) :3.44-3.65 (3H,m) 7.40-7.54 (3H,m), 7.59(1H,dd,J=8Hz,4Hz),7.68(1H,d,J=8Hz),8.15(1H,d,J=8Hz), 8.49(1H,d,J=4Hz),9.29(1H,brs),10.11(1H,brs),10..39(1H,brs) Preparation Example 73 5 According to the same manner as that of Preparation Example 5 except that N-[4-chloro-2-(hydrazinocarbonyl) 6-methyphenyl]-l-phenyl-3-trifluoromethyl-lH-pyrazole-5 carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2 10 pyridinyl) -3-trifluoromethyl-lH-pyrazole-5-carboxamide to obtain the present compound (73) of the formula:

F

3 0

H

3 C CI 0 CN N H (73) H O NN OCH 3 0 H H O The present compound (73) 'Hl-NMR(DMSO-d 6 )6(ppm):2.18 (3H,s),3.61(3H,s),7.37(lH,s), 15 7.49-7.55(7H,m),9.31(lH,brs),10.22(lH,brs),10.30(lH,brs) Preparation Example 74 According to the same manner as that of Preparation Example 72 except that 6-bromo-2-[1-(3-chloro-2-pyridinyl) 3-trifluoromethyl-lH-pyrazole-5-yl)-8-methyl-4H-3,1 20 benzoxazine-4-one was used in place of 2-[3-bromo-l-(3 chloro-2-pyridinyl)-lH-pyrazole-5-yl]-8-chloro-4H-3,1- 350 benzoxazine-4-one to obtain the present compound (74) of the formula:

F

3 C

H

3 C Br 0 N N H (74) H -N OCH 3 C1 It, 0 N C N O T H 0 The present compound (74) 5 'H-NMR(DMSO-d6,TMS)5(ppm):2.15(3H,s), 3 .5 6

-

3 .65( 3 H,m), 7

.

47 7.55(lH,m),7.62-7.75(3H,m),8.22(1H,d,J=8Hz),8.53(1H,d, J=4Hz),9.31(1H,brs),10.17(1H,brs),10.38(lH,brs) Preparation Example 75 According to the same manner as that of Preparation 10 Example 72 except that 2-[1-(3-chloro-2-pyridinyl) 3-trifluoromethyl-1H-pyrazole-5-yl]-6-iodo-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 2- [3-bromo-1- (3-chloro 2-pyridinyl)-1H-pyrazole-5-yl]-8-chloro-4H-3,1-benzoxazine 4-one to obtain the present compound (75) of the formula:. H3C

F

3 C H0C N N H (75) N H -N, OCHa 0 N T 11N H 0 15 The present compound (75) lH-NMR(DMSO-dsTMS)6(ppm):2.12(3H,s),3.55- 3 .6 6

(

3 H,m), 7 .63-7.72(3H,m),7.83(1H,s),8.22(1H,d,J=8Hz),8.53(lH,d, J=4Hz) ,9.28 (lH,brs) ,10.14 (lH,brs),10.35 (lH,brs) 351 Preparation Example 76 A mixture of 0.18g of N-(4-chloro-2 (hydrazinocarobnyl) -6-methylphenyl) -3- (2-chlorophenyl) -1 methyl-lH-pyrazole-4-carboxamide, 45mg of methyl 5 chloroformate, 68mg of pyridine and 5ml of acetonitrile was prepared under ice-cooling, and the mixture was stirred at room temperature for 0.5 hour. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous 10 sodium sulfate, and concentrated under reduce pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.12g, of the present compound (76) of the formula:

H

3 C CI

H

3 C, O N N H (76) H -N

OCH

3 CI 0 N f H 6 15 The present compound (76) 'H-NMR(DMSO-d 6 )6(ppm):2.13(3H,s),3'37-3.67(6H,m),7.37(lH, brs),7.42-7.52(4H,m),7.60(1H,d,J=8Hz),8.13(lH,s),9.28-9.37 (2H,m),-10.13(lH,brs) Preparation Example 77 20 According to the same manner as that of Preparation Example (76) except that N- (4-chlolro-2- (hydrazinocarhbonyl) 6-methylphenyl]-5-(2-chlorophenyl)-1-mehyl-lH-pyrazole-4- 352 carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl) -6-mehylphenyl) -3- (2-chlorophenyl) -1 metiyl-lH-pyrazole-4-carboxamide to obtain the present compound (77) of the formula:

H

3 C C1

N

H

3 C'N N H (77) H -N

OCH

3 Ci O N H 0 5 The present compound (77) 'H-NMIR(DMSO-d 6 )5(ppm):2.17(3H,s),3.46-3.62(3H,m),3.94(3H, s),7.32-7. 41(4H,m) ,7. 44-7.46(lH,m) ,7.50 (1H,s),8.36 (1H, s), 9.30-9.34 (2H,m),10.17 (lH,brs) 10 Preparation Example 78 According to the same manner as that of Preparation Example 72 except that 2-[3-bromo-l-(3-chloro-2-pyridinyl) lH-pyrazole-5-yl]-6-chloro-8-methoxy-4H-3,1-benzoxazine-4 one was used in place of 2-[3-bromo-1-(3-ch,lQro-2-pyridinyl) 15 1H-pyrazole-5-yl]-8-chloro-4H-3,1-benzoxazine- 4 -one to obtain the present compound (78) of the formula: Br

H

3 CO

-

BrN N H (78) N H -N

OCH

3 0 N T - N H o The present compound (78) -353 'H-NMR(DMSO-d 6 ,TMS)5(ppm):3.56-3.64(3H,m), 3

.

77

-

3 .80( 3 H,m), 7.12(1H,brs),7.32(lH,brs),7.38(lH,brs),7.59(1H,dd,J=8Hz, 4Hz,,8.15(lH,d,J=8Hz),8.49(1H,d,J=4Hz),9.28(1H,brs),9.

9 5 (1H,brs),10.07(lH,brs) 5 Preparation Example 79 According to the same manner as that of Preparation Example 72 except that 2-[3-bromo-l-(3-chloro-2-pyridinyl) 1H-pyrazole-5-yl]-6-chloro-8-iodo-4H-3,1-benzoxazine-4-one was used in place of 2-[3-bromo-l-(3-chloro-2-pyridinyl)-lH 10 pyrazole-5-yl]-8-chloro-4H-3,1-benzoxazine-4-one to obtain the present compound (79) of the formula: Br C 'N HH .(79) Y ..H,-N OCH 3 0 N r N H 0 The present compound (79) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):3.56-3.64(38,m),7.43(lH,s),7.53 15 (lH,s)_,7.60(1H,dd,J=8Hz,4Hz) ,8.12-8.19(2H,m) ,8.50(lH,d, J=4Hz),9.34(1H,brs),10.16(1H,brs),10.47(1H,brs) Preparation Example 80 According to the same manner as that of Preparation Example 72 except that 2-[3-bromo-l-k3-chloro-2-pyridinyl) 20 1H-pyrazole-5-yl]-8-methoxy-4H-3,1-benzoxazne-4-one was used in place of 6 2-[3-bromo-l-(3-chloro-2-pyridinyl) 1H-pyrazole-5-yl]-8-chloro-4H-3,1-benzoxazine-4-one to 354 obtain the present compound (80) of the formula: Br

H

3 CO N H 5 - ,N OCH3 H O The present compound (80) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):3.52-3.64(3H,m), 3

.

74

(

3 H,s), 7 .07 5 7.14(lH,m),7.21(1H,d,J=8Hz),7.31-7.42(2H,m),7.59(1H, dd, J=8Hz,4Hz),8.15(1H,d,J=8Hz),8.49(1H,d,J=4Hz),9.21(lH,brs), 9.87(1H,brs),9.92(1H,brs) Preparation Example 81 According to the same manner as that of Preparation 10 Example 72 except that 2-[3-bromo-1-(3-chloro-2-pyridinyl) 1H-pyrazole-5-yl]-8-trifluoromethyl-4H-3,1-benzoxazine-4 one was used in place of 2-[3-bromo-1-(3-chloro-2 pyridinyl)-1H-pyrazole-5-yl)-8-chloro-4H-3,1-benzoxazine-4 one to obtain the present compound (81) of the formula: Br

F

3 C H -N CH CI O N 1 N H 0 15 The present compound (81) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):3.46-3.69(3H,m), 7

.

4 1(lH,s), 7 .59 (1H,dd,J=8Hz,4Hz),7.68(1H,t,J=8Hz),7.77-7.8 7 (lH,m), 7.90-7.97(1H,m),8.14(1H,d,J=8Hz),8.48(1H,d,J=4Hz),9.32(1H, .355 brs),10.14(1H,brs),10.48(1H,brs) Preparation Example 82 To a mixture of 0.25g of 3-chloro-2-(3 trifluoromethyl-lH-1,2,4-triazol-1-yl)pyridine and 5ml of 5 tetrahydrofuran was added dropwise 0.50ml of a 2.OM lithium diisopropylamide solution in heptane/tetrahydrofuran/ ethylbenzene at -78*C and the mixture was stirred at -78*C for 15 minutes. Carbon dioxide was introduced into the mixture at such a rate that an inner temperature was maintained at -60 0 C 10 or lower and, after the mixture turned yellow, the mixture was further stirred at -78 0 C for 10 minutes. The temperature of the reaction mixture was raised to room temperature, followed by concentration. A 2N aqueous sodium hydroxide solution was added to adjust the pH of the aqueous layer to 10 to 12, the 15 layers were separated, and the organic layer was extracted with a 0.5N aqueous sodium hydroxide solution. The aqueous layers were combined, and washed with chloroform, and 2N hydrochloric acid was added so that the pH of the aqueous layer became about 3, followed by extraction with ethyl acetate three times. The 20 organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 0.13g of crude 1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H-1, 2 ,4 triazole 5-carboxylic acid of the formula: 356

F

3 C O N, k"OH N CI N A mixture of 0.13g of the resulting crude 1- (3-chloro-2-pyridinyl) -3-trifluoromethyl-1H-1, 2,4 triazole 5-carboxylic acid and 0.10ml of thionyl chloride was 5 heated under reflux in 10ml of acetonitrile for 2 hours. The reaction mixture was allowed to cool to room temperature, and concentrated under reduced pressure, the resulting residue was dissoLved in 10ml of acetonitrile, 0.11g of N-(2-amino-5-chloro-3-methylbenzoyl)-N' 10 methoxycarbonylhydrazine and 0.10ml of diisopropylethylamine were added, and the mixture was stirred at room temperature for 16 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate two times. The organic layers were combined, washed with an aqueous saturated sodium 15 chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 12mg of the present compound (82) of the formula:

F

3 C

H

3 C CI N, W N H (82) N H .... N

OCH

3 CI 0 N r "N H O 357 The present compound (82) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.31(3H,s),3.64(3H,s),7.40(lH,s), 7.60(lH,s),7.90(lH,brs),8.77(lH,d,J=7Hz),9.33(IH,brs),9.50 (1H,brs),10.27(lH,brs),10.44(l1H,brs) 5 Preparation Example 83, According to the same manner as that of Preparation Example 5 except that N-[4-chloro-2-(hydrazinocarbonyl)-6 methyphenyl]-1-ethyl-3-trifluoromethyl-lH-pyrazole-5 carboxamide was used in place of N-[4-chloro-2 10 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2 pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-cadrboxamide to obtain the present compound (83) of the formula:

F

3 C

H

3 C CI 0N 'N H H (83) I -N OCH3

CH

2

CH

3 0 N jf H 0 The present compound (83) 15 'H-NMR(DMSO-d 6 )6(ppm):1.37(3H,t,J=7Hz),2.26(3H,s),3.60(3H, s),4.55(2H,q,J=7Hz),7.41(2H,s),7.58(1H,s),9.26(lH,brs), 10.12(lH,brs),10.18 (lH,brs) Preparation Example 84 According to the same manner as that of Preparation 20 Example 76 except that 1-tert-butyl-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-5-(2-chlorophenyl)-1H pyrazole-4-carboxamide was used in place of N-[4-chloro-2- 358 (hydrazinocarbonyl) -6-methylphenyl) -3- (2-chlorophenyl) -1 methyl-lH-pyrazole-4-carboxamide to obtain the present compound (84) of the formula:

H

3 C Ci

N-

N NH

(H

3

C)

3 C..- N H (84) H -N OCH 3 (4 Ci 0 N H 5 The present compound (84) 1H-NMR(DMSO-d 6 )6(ppm):1.39(9H,s),2.05(3H,s), 3

.

4 7- 3

.

62

(

3 H, m),7.,36-7.53(6H,m),8.10(1H,s),9.19-9.26(2H,m),10.1 2 (lH,brs) Preparation Example 85 According to the same manner as that of Preparation 10 Example 72 except that 2-[3-bromo-l-(3-chloro-2 pyridinyl)-lH-pyrazole-5-yll-7-chloro-8-methyl-4H- 3 ,1 benzoxazine-4-one was used in place of 2- [3-bromo-l- (3-chloro 2-pyridinyl)-1H-pyrazole-5-yll-8-chloro-4H-3,1-benzoxazine 4-one to obtain the present compound (85) of the formula: Ci Br \ H 3 C BNN N H (85) H -N OCH3 0 N y Cl O N N H O 15 The present compound (85) H-NMR(DMSO-d 6 ,TMS) 5(ppm):2.17(3H,s),3.60-3.65( 3 H,m), 7 .35- 359 7

.

4 3(2H,m),7.54(1H,d,J=8HZ),7.61(lH,dd,J=BHz,4Hz),8.

17 (lH, d,J=8Hz),8.50(1H,d,J=4Hz),9.28(1H,brs),10.14(lH,brs),10.

41 (1H,brs) Preparation Example 86 5 According to the same manner as that of Preparation Example 5 except that N-[4-chloro-2-(hydrazinocarbonyl) 6-methyphenyl]-1-isopropyl-3-trifluoromethyl-1H-pyrazole-5 carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2 10 pyridinyl) -3-trifluoromethyl-1H-pyrazole-5-carboxamide to obtain the present compound (86) of the formula: H3C C1

F

3 C O / N, N H (86) N HH NI H -N OCH 3

CH(CH

3

)

2 0 N r H . The present compound (86) 'H-NMR(DMSO-dd)6(pm):1.43(6H,d,J=6Hz),2.26(3H,s),3.60( 3 H, 15 s),5.41-5.45(1H,m),7.35(lH,s),7.40(lH,s),7.59(1H,s), 9

.

2 6 (lH,brs),10.10(1H,brs),10.1 7 (lH,brs) Preparation Example 87 According to the same manner as that of Preparation Example 72 except that 2-[3-bromo-1-(3-chloro-2-pyridinyl) 20 1H-pyrazole-5-yl]-5,8-dichloro-4H-3,1-benzoxazine-4-one was used in place of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H pyrazole-5-yl)-8-chloro-4H-3,1-benzoxazine-4-one to obtain ,360 the present compound (87) of the formula: C1 Br OC/ N \ N CI 17 'N H NH OCH 3 (87) CI 0 N' H O The present compound (87) H-NMR(DMSO-d 6 ,TMS)(ppm):3.50-3.68(3H,m), 7

.

47 (lH,s), 7

.

52 5 7.65(3H,m),8.17(1H,d,J=8Hz),8.49(lH,d,J=4Hz),9.43(lH,brs), 10.17(1H,brs),10.47(1H,brs) Preparation Example 88 According to the same manner as that of Preparation Example 72 except that 2-[3-bromo-l-(3-chloro-2-pyridinyl) 10 1H-pyrazole-5-yl)-5-chloro-8-methyl-4H-3,1-benzoxazine-4-on e was used in place of 2-[3-bromo-l-(3-chloro-2-pyridinyl) 1H-pyrazole-5-yl)-8-chloro-4H-3,1-benzoxazine-4-one to obtain the present compound (88) of the formula:

H

3 C Br O N N C( 'N H NH OCH 3 (88) Ci 0 N' I N H 0 15 The present compound (88) H-NMR(DMSO--d 6 ,TMS)5(ppm):2.09(3H,s),3.5 1

-

3

.

68

(

3 H,m), 7

.

3 1 7.45(3H,m),7.61(lH,dd,J=BHz,4Hz),8.19(lH,d,J=8Hz),8.49(lH, d,J=4Hz),9.43(lH,brs),10.04(1H,brs),10.13(1H,brs) Preparation Example 89 ,361 According to the same manner as that of Preparation Example 5 except that N-[4-chloro-2-(hydrazinocarbonyl) 6-methyphenyl]-1-tert-butyl-3-trifluoromethyl-1H-pyrazole 5-carboxamide was used in place of N-[4-chloro-2 5 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyridinyl )-3-trifluoromethyl-lH-pyrazole-5-cadrboxamide to obtain the present compound (89) of the formula:

F

3 C

H

3 C C 0 NN H (89) H -N

OCH

3

C(CH

3

)

3 0 N H o The present compound (89) 10 1 H-NMR(DMSO-d 6 )6(ppm) :1.67(9H,s),2.28(3H,s),3.64(3H,s),7.11 (lH,s),7.42(lH,s),7.55(1H,s),9.29(1H,brs),10.18(1H,brs), 10.23 (lH,brs) Preparation Example 90 According to the same manner as that of Preparation 15 Example 5 except that N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl]-1-tert-butyl-5-trifluoromethyl-lH-pyrazole 3-carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro-2 pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carboxamide to 20 obtain the present compound (90) of the formula: 362

H

3 C C1 F3C 0 (H3C)3CN N H (90) -, N OCH 3 H . The present compound (90) 'H-NMR(DMSO-d 6 )5(ppm):1.69(9H,s),2.26(3H,s),3.57(3H,s),7.

43 (1H,s),7.62(1H,d,J=2Hz),7.82(lH,d,J=2Hz),9.30(lH,brs),10.

2 3 5 (1H,brs),10.56(1H,brs) Preparation Example 91 According to the same manner as that of Preparation Example 72 except that 2- [3-bromo-l- (3-chloro-2-pyridinyl) 1H-pyrazole-5-yl] -8-methyl-4H-3, 1-benzoxazine-4-one was used 10 in place of 2-[3-bromo-1-(3-chloro-2-pyridinyl) 1H-pyrazole-5-yl]-8-chloro-4H-3,1-benzoxazine-4-one to obtain the present compound (91) of the formula: Br

H

3 C 0 BrN/ N H (1 N H -N

OCH

3 C N O N--r H O The present compound (91) 15 1H-NMR(DMSO-d,TMS)5(ppm):2.15(3H,s),3.55- 3

.

67

(

3 H,m), 7

.

25 7.45(3H,m),7.61(1H,dd,J=8Hz,4Hz),7.94-7.97(lH,m),8.17(1H,d, J=8Hz),8.48-8.53(1H,m),9.25(1H,brs),10.04(1H,brs),10.

2 0(lH, brs) Preparation Example 92 -363 According to the same manner as that of Preparation Example 72 except that 8-bromo-2-[3-bromo-1-(3-chloro 2-pyridinyl)-1H-pyrazole-5-yl]- 4

H-

3 , 1-benzoxazine-4-one was used in place of 2-[3-bromo-1-(3-chloro-2-pyridinyl) 5 1H-pyrazole-5-yl]-8-chloro-4H-3,1-benzoxazine-4-one to obtain the present compound (92) of the formula: Br Br N H H (92) H - N TOCH3 CI ON N N H O The present compound (92) 'H-NMR(DMSO-d6 ,TMS) 5(ppm):3.4.5-3.67(3H,m),7.

34

-

7

.

44

(

2 H,m), 10 7.53(lH,s),7.60(1H,dd,J=8Hz,4Hz),7.84(lH,d,J=8Hz),8.15(1H, d,J=8Hz),8.50(1H,d,J=4Hz),9.29(lH,brs),10.08(1H,brs),10.

42 (lH,brs) Preparation Example 93 A mixture of 0.20g of 4-bromo-N-[4-chloro-2 15 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2-pyridinyl )-1H-pyrrole-2-carboxamide, 0.05g of methyl chloroformate and 0. 07ml of pyridine in N, N-dimethylformamide was stirred at room temperature for 8 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by 20 filtration to obtain 0.16g of the present compound (93) of the formula: 364

H

3 C Cl N N H (93) H -N OCH 3 N

-

H O The present compound (93) 'H-NMR(DMSO-d 6 )5(ppm):2.16(3H,S),3.63(3H,S), 7

.

23 (lH,s), 7

.

4 1 (1H,d,J=2Hz),7.48-7.51(3H,m),8.05(lH,dd,J=8HZ,2Hz),8.

43 (lH, 5 dd,J=5Hz,2Hz)9.31(1H,brs),9.75(lH,brs),10.12(lH,brs) Preparation Example 94 A mixture of 0.26g of 3-bromo-N-[4-chloro-2-(N' isopropylhydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2 pyridinyl)-1H-pyrazole-5-carboxamide, 0.06ml of methyl 10 chloroformate and 2ml of pyridine was stirred at room temperature for 1.5 hours. Water was poured into the reaction mixture, and the mixture was extracted with methyl t-butyl ether three times. The organic layers were combined, washed successively with 1N hydrochloric acid, an aqueous saturated 15 sodium bicarbonate solution and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.18g of the present compound (94) of the formula: .365 Br H 3 C CI 0 N' N CH(CH 3

)

2 (g4 .H N OCH 3 I N

-

H O The present compound (94) 1H-NMR (DMSO-d 6 , 80C) (ppm) :1. 03 (6H, d, J=7Hz) , 2 .1 8

(

3 H, s) , 3

.

53 (3H,s),4.24(lH,hept.,J=7Hz),7.29(1H,s),7.37(1H,d,J=2Hz), 5 7.49(1H,d,J=2Hz),7.57(lH,dd,J=8Hz,4Hz),8.10(lH,dd,J=8Hz, 1Hz),8.45(lH,dd, J=4Hz,1Hz),9.92(1H, s), 9.98 (lH, s) Preparation Example 95 To a mixture of 4.llg of the present compound (34), 1.45ml of triethylamine and 80ml of tetrahydrofuran was added dropwise 10 0.69ml of methyl chloroformate under ice-cooling. After the resulting mixture was stirred at room temperature for 1 hour, water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride 15 solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 2.66g of the present compound (95) of the formula: Br H 3 C CI N'N

OCH

3 (95) CI OZ N-N N H 0>-OCH 3 1!50 366 The present compound (95) 'H-NMR(CDC3,TMS)5(ppm):2.22(3H,s),3.82(6H,s),6.

99 (lH,S), 7.34-7.37(2H,m),7.41(1H,d,J=2Hz),7.88(lH,dd,J=8Hz,lHz), 8

.

37 (1H,dd,J=4Hz,lHz),8.43(lH,s),9.21(1H,s) 5 Preparation Example 96' A mixture of 0. 11g of N- [ 4-chloro-2- (hydra zinocarbonyl) 6-methylphenyl]-1-(3-chloro-2-pyridinyl) -3-iodo-lH pyrazole-5-carboxamide, 0.095ml of methyl chloroformate and 2ml of pyridine were mixed, and the mixture was stirred at room 10 temperature for 2.75 hours. Water and toluene were poured into the reaction mixture, followed by concentration under reduced pressure. The residue was distributed between water and ethyl acetate, and the organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous 15 magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.11g of the present compound (96) of the formula:

H

3 C C1 N N H (96) N H .. N OCH3 N O N N H O 20 The present compound (96) 1H-NMR(DMSO-d)5(ppm):2.15(3H,s),3.63(3H,brs), 7

.

4 0( 2 H,brs), 7.54(1H,s),7.59(1H,dd,J=8Hz,4Hz),8.15(1H,d,J=8Hz),8.49(1H, .367 d,J=4Hz),9.31(lH,brs),10.16(2H,brs) Preparation Example 97 A mixture of 0.27g of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro-2 5 pyridinyl)-lH-pyrazole-5-carboxamide, 0.13ml of methyl chloroformate and 3ml of pyridine was stirred at room temperature for 1. 75 hours. Water and toluene were poured into the reaction mixture, followed by concentration under reduced pressure. The residue was distributed between water and ethyl 10 acetate, and the organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.24g of the present compound (97) of 15 the formula: Br H 3 C CI 0 N N H (97) H -N

OCH

3 C N 0 N H O The present compound (97) lH-NMR(DMSO-d,80O*C)5(ppm):2.14(3H,s),3.59(3H,brs), 7

.

4 3(1H, s),7.48(lH,s),7.57(1H,dd,J=BHz,4Hz),8.03(lH, s),8.12(lH,d,J= 20 8Hz),8.47(lH,d,J=4Hz),8.94(lH,brs),9.81(lH,brs),10.11(l H, brs) -368 Preparation Example 98 A mixture of 0.30g of N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyll -1- (3-chloro-2-pyridinyl) -3-phenyl-lH pyrazole-5-carboxamide, 0. 15ml of methyl chloroformate and 3ml' 5 of pyridine was stirred at room temperature for 1.75 hours. Water and toluene were poured into the reaction mixture, followed by the concentration under reduced pressure. The residue was distributed between water and ethyl acetate, and the organic layer was washed with an aqueous saturated sodium 10 chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column, chromatography to obtain 0.30g of the present compound (98) of the formula:

H

3 C C1 0 / N'N N H (98) 'N H .. N

OCH

3 ( C1 N 0 N H 0 15 The present compound (98) 1H-NMR(DMSO-d 6 )5(ppm):2.19(3H,s),3.62(3H,brs), 7

.

42

-

7 .5 2

(

4 H, m),7.55(lH,brs),7.60(lH,dd,J=8Hz,4Hz),7.70(lHbrs), 7 .88( 2 H, d,J=7Hz),8.17(lH,dd,J=8Hz,lHz),8.32(lH,dd,J=4Hz,lHz), 9

.

3 4 (lH,brs),10.19(2H,brs) 20 Preparation Example 99 A mixture of 0.27g of N-[4-chloro-2-(hydrazinocarbonyl)- ,369 6-methylphenyl] -1- (3-chloro-2-pyridinyl) -3-methylthio-lH -pyrazole-5-carboxamide, 0.14ml of methyl chloroformate and 3ml of pyridine was stirred at room temperature for 2 hours. Water and toluene were poured into the reaction mixture, 5 followed by concentration under reduced pressure. The residue was distributed between water and ethyl acetate, and the organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was 10 subjected to silica gel column chromatography to obtain 0.14g of the present compound (99) of the formula: H3C CI

H

3 CS O / N N H (99) H -N OCH 3 C1 0 N N H The present compound (99) 'H-NMR(DMSO-d 6 )6(ppm):2.16(3H,s),2.54(3H,s)3.62(3H,brs), 15 7.20(lH,s),7.38(lH,brs),7.54-7.58 (2H,m),8.13(lH,dd,J=8Hz, 1Hz),8.48(lH,dd,J=4Hz,1.5Hz),9.32(1H,brs),10.11(lH,s),10.14 (lH,s) Preparation Example 100 A mixture of 0.20g of 6-chloro-2-[l-(3-chloro 20 2-pyrizinyl)-3-methylsulfonyl-lH-pyrazol-5-yl]-8-methyl 4H-3, 1-benzoxazine-4-one, 0.40g of methyl carbazate and 8ml of 370 N,N-dimethylformamide was stirred at room temperature for 22 hours. Water was poured into the reaction mixture, the mixture was extracted with methyl t-butyl ether three times. The organic layers were combined, washed successively with water' 5 and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.13g of the present compound (100) of the formula:

H

3 Cs,0 H3C C 'N N H (100) H -N OCH 3 C O N N H 0 10 The present compound (100) 'H-NMR(DMSO-de)5(ppm):2.16(3H,s),3.39(3H,s) 3 .6 2

(

3 H,brs), 7.39(lH,brs),7.56(1H,s),7.67(1H,dd,J=8Hz,4Hz),7.78(lH,s), 8.23(lH,dd,J=8Hz,lHz),8.54(lH,dd,J=4Hz,lHz),9.31(lH,brs), 15 10.16(lH,brs),10.41(lH,brs) Preparation Example 101 A mixture of 0.10g of 6-chloro-2-[l-(3-chloro-2 pyridinyl) -3-methylsulfinyl-H-pyrazol-5-yl]-8-methyl-4H 3,1-benzoxazine-4-one, 0.21g of methyl carbazate and 4ml of 20 N,N-dimethylformamide was stirred at room temperature for 20 hours. Water was poured into the reaction mixture, and the .371 mixture was extracted with methyl t-butyl ether three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under 5 reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.092g of the present compound (101) of the formula:

H

3 C "

H

3 C Cl S / N_ N H (101) H -N

OCH

3 C0 0 N N H The present compound (101) 10 'H-NMR(DMSO-d 6 )5(ppm):2.16(3H,s),2.99(3H,s)3.62(3H,brs), 7.39(lH,brs),7.55(lH,s),7.64(1H,dd,J=8Hz,4Hz),7.74(1H,s), 8.20(1H,dd,J=8Hz,1.5Hz),8.52(1H,dd,J=4Hz,lHz),9.32(1H,brs), 10.15(lH,brs),10.35(1H,brs) Preparation Example 102 15 Amixture 0.12g of 6-chloro-2-[1-(3-chloro-2-pyridinyl) 3-methyl-1H-pyrazole-5-yl)-8-methyl-4H-3,1-benzoxazine-4 one, 0.27g of methyl carbazate and 4ml of N,N-dimethylformamide was stirred at room temperature for 24 hours. Water was poured into the reaction mixture, and the mixture was extracted with 20 methyl t-butyl ether three times. The organic layers were combined, washed successively with water and an aqueous 372 saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.lOg of the present compound (102)' 5 or the formula:

H

3 C

H

3 C C1 N HN N HH (102) H" ' -,N OCH3 C.- 0 N N H O The present compound (102) lH-NMR(DMSO-d 6 )5(ppm):2.15(3H,s),2.31(3H,s) 3 .6 2

(

3 H,brs), 7.02(1H,s),7.40(1H,brs),7.52-7.55(2H,m),8.11(1H,dd,J=8Hz, 10 1Hz),8.46(1H,dd,J=4Hz,lHz),9.31(lH,brs),10.03(lH,brs),10.14 (1H,brs) Preparation Example 103 According to the same manner as that of Preparation Example 10 except that 15 N- [2- (hydrazinocarbonyl) -3-methylphenyl) 1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazole-5 carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2-pyridinyl )-3-trifluoromethyl-1H-pyrazole-5-carboxamide to obtain the 20 present compound (103) of the formula: 373

F

3 C O N' N CH 3 (103) N H NH N(CH 3

)

2 CI O N < N H 0 The present compound (103) 1H-NMR(DMSO-d6)6(ppm):2.29(3H,s),2.93(6H,s), 7 .0 7 (lH,d, J=8Hz),7.27(lH,t,J=8Hz),7.71(1H,dd,J=8Hz,4Hz),7.86(1H,d, 5 J=8Hz),8.11(1H,s),8.28 (1H,d,J=8Hz),8.56(1H,d,J=4Hz),8.99 (lH,brs),10.10(lH,brs),10.19(1H,brs) Preparation Example 104 A mixture of 0.20g of 6-chloro-2-[1-(3-chloro-2 pyridinyl) -3-isopropyl-lH-pyrazol-5-yl) -8-methyl-4H-3, 1-ben 10 zoxazine-4-one, 0.43g of methyl carbazate and 5ml of N,N-dimethylformamide was stirred at room temperature for 20 hours. Water was poured into the reaction mixture, and the mixture was extracted with methyl t-butyl ether three times. The organic layers were combined, washed successively with 15 water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.22g of the present compound (104) of the formula: 374 H3C C1

(H

3

C)

2 HC H 0 'N N H (104) H ... N OCH 3 CI ,N H The present compound (104) 'H-NMR(DMSO-d 6 )5(ppm):1.35(6H,d,J=7Hz),2.22(3H,s), 3 .08(lH, hept.,J=7Hz),3.68(3H,brs),7.17(1H,s),7.45(1H,brs), 7

.

5 8- 7 .62 5 (2H,m),8.17(lH,dd,J=8Hz,lHz),8.52(lH,dd,J=4Hz,lHz),9.

39 (l1M, brs),10.09(lH,brs),10.20(1H,brs) Preparation Example 105 A mixture of 0.20g of 2-.[1-(3-chloro-2-pyridinyl) 3-isopropyl-lH-pyrazol-5-yl)-6,8-dibromo-4H-3,1 10 benzoxazine-4-one, 0.34g of methyl carbazate and 4ml of N,N-dimethylformamide was stirred at room temperature for 17 hours. Water was poured into the reaction mixture, and the mixture was extracted with methyl t-butyl ether three times. The organic layers were combined, washed successively with 15 water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0. 16g of the present compound (105) of the formula: 375

(H

3

C)

2 HC Br Br N'N N H (105) N H -N OCH3 H o The present compound (105) 'H-NMR(DMSO-d 6 )6(ppm):1.27(6H,d,J=7Hz),3.01(lH,hept., J=7Hz),3.60(3H,brs),7.16(lH,s),7.53(1H,dd,J=8Hz, 4 Hz), 7

.

64 5 (lH,brs),8.07(lH,dd,J=8Hz,lHz),8.11(1H,brs),8.

4 5(lH,dd, J=4Hz,lHz).9.35(1H,brs),10.16(1H,brs),10.

22 (1H,brs) Preparation Example 106 According to the same manner as that of Preparation Example 95 except that the present compound (59) was used in 10 place of the present compound (34) to obtain the present compound (106) of the formula:

F

3 C Br CI N H >-OCH 3 (106) CI 0 N-N N H 0>-OCH 3 The present compound (106) "H-NMR(CDC1 3 ,TMS)6(ppm):3.73(6H,s),7.38-7.

4 5

(

3 H,m), 7

.

64 (lH, 15 d,J=2Hz),7.89(1H,d,J=8Hz),8.37(1H,d,J=4Hz),8.67(1H,brs), 9.21 (1H,brs) Preparation Example 107 376 According to the same manner as that of Preparation Example 95 except that the present compound (70) was used in place of the present compound (34) to obtain the present compound (107) of the formula: Br CI Br O C N, N (107) N H-OCH 3 CI O N-N H -OCH 3 5 0 The present compound (107) H-NMR(CDCl 3 ,TMS)5(ppm):3.77(6H,s),7.09(lH,s), 7

.

36 (lH,dd, J=BHz,4Hz),7.51(1H,d,J=2Hz),7..69(lH,d,J=2Hz),7.88(1H,dd, J=8Hz,lHz),8.35(lH,dd,J=4Hz,1Hz),8.63(1H,brs),8.

95 (lH,brs) 10 Preparation Example 108 According to the same manner as that of Preparation Example 95 except that the present compound (5) was used in place of the present compound (34) to obtain the present compound (108) of the formula: H3C C1

F

3 C 0 N ' 0 N'N H YOCH 3 (108) CI 0 N-N N H 0r-OCH 3 15 0 The present compound (108) 1H-NMR(CDCl 3 ,TMS)5(ppm):2.23(3H,s), 3

.

8 1( 6 H,s), 7

.

24 (lH,s), 377 7.36(1H,d,J=2HZ),7.39-7.42(2H,m),7.91(lH,dd,J=8Hz,1Hz), 8.28(1H,s),8.40(1H,dd,J=4Hz,1Hz),9.27(1H,s). Preparation Example 109 According to the same manner as that of Preparation 5 Example 95 except that the present compound (49) was used in place of the present compound (34) to obtain the present compound (109) of the formula:

F

3 C Br Br N H _-OCH3 C1 O N-N I NN H OCH3 The present compound (109) 10 'H-NMR(CDCl 3 ,TMS)5(ppm):3.75(6H,s),7.37- 7

.

43

(

2 H,m), 7 .6 3 (lH, d, J=2Hz),7.84 (1H,d,J=2Hz),7.90(1H,dd,J=8Hz,1Hz),8.38(lH,dd, J=4Hz,J=lHz),8.57(1H,brs),9.17(1H,brs). Preparation Example 110 According to the same manner as that of Preparation 15 Example 95 except that the present compound (68) was used in place of the present compound (34) to obtain the present compound (110) of the formula: -378 Br 0Br Br r\, 0 'N H \ -OCH 3 CI O N-N N H , rOCH 3 The present compound (110) 'H-NMR(CDC1 3 ,TMS)5(ppm) :3.78 (6H,s) ,7.08 (lH,s) ,7.37 (1H,dd,J= 8Hz,4Hz),7.67(1H,d,J=2Hz),7.87-7.90(2H,m),8.35(1H,dd,J=4Hz, 5 lHz),8.54(1H,brs),8.88(1H,brs). Preparation Example 111 According to the same manner as that of Preparation Example 95 except that ethyl chloroformate was used in place of methyl chloroformate to obtain the present compound (111) 10 of the formula: Br H 3 C CI 0 N H _ OCH 2

CH

3 CI O N-N N H 0r-OCH 3 The present compound (111) 1 H-NMR(CDCl 3 ,TMS) 5 (ppm) :1.30 (3H, t, J=7Hz) ,2.24 (3H, s) ,3.82 (3H,s),4.30(2H,q,J=7Hz),6.97(1H,s),7.34-7.38(2H,m),7.45(1H, 15 s),7.88(1H,dd,J=8Hz,2Hz),8.27(1H,s),8.38(1H,dd,J=5Hz,2Hz), 9.21(1H,s). Preparation Example 112 379 According to the same manner as that of Preparation Example 95 except that isobutyl chloroformate was used in place of methyl chloroformate to obtain the present compound (112) of the formula: Br

H

3 C CI 0 N H -OCH 2

CH(CH

3

)

2 C1 0 N-N N H 5 The present compound (112) IH-NMR(CDCl 3 ,TMS)5(ppm):0.94(6H,d,J=7Hz),1.98(1H,hept, J=7Hz),2.24(3H,s),3.82(3H,s),.4.04(2H,d,J=7Hz),6.

9 6 (lH,s), 7.34-7.37(2H,m),7.45(1H,d,J=2Hz),7.88(1H,dd,J=8Hz,2Hz),8.

29 10 (1H,s),8.38(1H,dd,J=5Hz,2Hz),9.23(1H,s). Preparation Example 113 A mixture of 0.10g of 6-chloro-2-[1-(3-chloro-2 pyridinyl)-3-cyano-lH-pyrazole-5-yl]-8-methyl-4H-3,1 benzoxazine-4-one, 0.23g of methyl carbazate and 4ml of 15 N,N-dimethylformamide was stirred at room temperature for 18 hours. Water was poured into the reaction mixture, and the mixture was extracted with methyl t-butyl ether three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried 20 over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to 380 silica gel column chromatography to obtain 0.090g of the present compound (113) of the formula: NC H 3 C C1 0 NN N H (113) H -N OCH 3 ( N H O The present compound (113) 5 'H-NMR(DMSO-d 6 )6(ppm):2.14(3H,s),3.61(3H,brs), 7

.

38 (1H,brs), 7.54(lH,s),7.67(1H,dd,J=8Hz,5Hz),7.81(1H,s),8.22(1H,d, J=8Hz),8.53(1H,d,J=5Hz),9.29(1H,brs),10.16(1H,brs),10.

4 4 (1H,brs). Preparation Example 114 10 A mixture of 0.30g of 2-[3-bromo-l-(3-chloro-2 pyridinyl)-1H-pyrazole-5-yl]-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one, 0.69g of N-methyl-N methoxycarbonylhydrazine and 15ml of N,N-dimethylformamide was stirred at 60*C for 9 hours and at 80*C for 22 hours,. Water 15 was poured into the reaction mixture, and the mixture was extracted with methyl tert-butyl ether three times. The organic layers were combined, washed with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. 20 The residue was subjected to silica gel column chromatography to obtain 0.036g of the present compound (114) of the formula: -381 Br H 3 C C1 0 N N CH 3 (114) N H . OCH 3 N H O The present compound (114) 1 H-NMR(CDCl 3 ,TMS)6(ppm):2.20(3H,s),3.21(3H,s), 3

.

7 4

(

3 H,brs), 7.05(1H,s),7.26-7.38(3H,m),7.86(1H,dd,J=8Hz,2Hz),8.03 5 (1H,s),8.42(1H,dd,J=5Hz,2Hz),9.47(1H,s). Preparation Example 115 A mixture of 0.60g of 3-bromo-N-[4-chloro-2-(N methylhydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2 pyridinyl)-1H-pyrazole-5-carboxamide, 0.41ml of methyl 10 chloroformate and 6ml of pyridine was stirred at room temperature for 3 hours. Water was poured into the reaction mixture, followed by concentration under reduced pressure. The residue was distributed between water and ethyl acetate, and the organic layer was washed with an aqueous saturated sodium 15 chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.46g of the present compound (115) of the formula: .382

H

3 C CI Br 0 NH (115) N H N OCH 3 CI N O0 f ' H 3 C O The present compound (115) 'H-NMR(CDCl,TMS)6(ppm):2.04(3H,s),3.22(3H,s), 3

.

57

(

2

.

6 H,s), 3.80(0.4H,s),7.01(1H,s),7.04(lH,s),7.28(1H,s),7.40(1H,dd, 5 J=8Hz,5Hz),7.61(1H,brs),7.87(1H,dd,J=8Hz,2Hz),8.46(lH,dd, J=5Hz,2Hz),9.80(1H,brs). Preparation Example 116 According to the same manner as that of Preparation Example 72 except that 2-[3-bromo-1-(3-chloro-2 10 pyridinyl)-1H-pyrazole-5-yl]-6,7-dichloro-8-methyl- 4 H-3,1-b enzoxazine-4-one was used in place of 2-[3-bromo-1-(3-chloro 2-pyridinyl) -1H-pyrazole-5-yl) -8-chloro-4H-3, 1-benzoxazine 4-one to obtain the present compound (116) of the formula: CI Br

H

3 C CI 'N H H (116) H 0 N OCH3 N H 0 15 The present compound (116) 'H-NMR(DMSO-d6,TMS)(ppm):2.25(3H,s),3.45- 3 .6 8

(

3 H,m), 7

.

3 6 (1H,s),7.57-7.65(2H,m),8.18(1H,d,J=8Hz),8.50(1H,d,J=4Hz), .383 9.36(1H,brs),10.24 (1H,brs),10.49(1H,brs). Preparation Example 117 According to the same manner as that of Preparation Example 72 except that 2-[3-bromo-1-(3-chloro-2-pyridinyl)-' 5 1H-pyrazole-5-yl)-8-methyl-6-cyano- 4 H-3, 1-benzoxazine-4-one was used in place of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H pyrazole-5-yll-8-chloro-4H-3,1-benzoxazine-4-one to obtain the present compound (117) of the formula: Br\

H

3 C CN H -N

OCH

3 0 N y 10 The present compound (117) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.20(3H,s),3.45-3.68( 3 H,m), 7

.

3 8 (1H, s),7.61(1H, dd, J=8Hz, 5Hz), 7.77 (1H, s),7.96(1H, s),8.17 (1H, d,J=8Hz),8.50(1H,d,J=5Hz),9.36(lH,brs),10.27(lH,brs),10.

49 (1H,brs). 15 Preparation Example 118 A mixture of 0.59g of 3,5-dibromo-2-{N-[3-bromo-1 (3-chloro-2-pyridinyl)-1H-pyrazole-5-carbonyl]-N methylaminolbenzoic acid, 2ml of thionyl chloride and one droplet of N,N-dimethylformamide was stirred at 80*C for 1 hour. 20 The reaction mixture was concentrated under reduced pressure, 10ml of hexane was added thereto, and the mixture was further 384 concentrated under reduced pressure. The resulting residue, 10ml of tetrahydrofuran, 0.10g of methyl carbazate and 1ml of pyridine were mixed, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into' 5 30ml of water, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was 10 subjected to silica gel column chromatography to obtain 0.23g of the present compound (118) of the formula: Br 0Br Br N, NN

H

3 C -YN OCH3 N H 6 The present compound (118) 1 H-NMR(DMSO-d 6 ,TMS)5(ppm) :3.05(l.9H,s),3.38(1.lH,s), 15 3.52-3.73(3H,m),5.68(0.7H,brs),7.11(0.3H,brs),7.57-7.81(2H, m),8.16-8.32(2H,m),8.49-8.55(1H,m),9.42(lH,brs),10.5 4 (lH, brs). Preparation Example 119 A mixture of 0.30g of 3-bromo-N-[4-chloro-2-(N,N' 20 dimethylhydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2 pyridinyl)-lH-pyrazole-5-carboxamide, 0.07ml of methyl 385 % chloroformate and 5ml of pyridine was stirred at room temperature for 1 hour. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, dried over anhydrous' 5 sodium sulfate, and concentrated under reduced pressure. The resulting residue was washed with a mixed solvent of ethyl acetate and hexane to obtain 0.09g of the present compound (119) of the formula: Br

H

3 C CI N/ N CH 3 H -N OCH 3

H

3 C 0 10 The present compound (119) 'H-NMR(DMSO-dE,TMS)5(ppm):2.10-2.24(3H,m), 2 .61- 2

.

87

(

3 H,m), 2.90-3.18(3H,m),3.45-3.74(3H,m),7.12-7.30(1H,m), 7

.

33 -7.

44 (1H,m),7.44-7.58(lH,m),7.58-7.66(1H,m),8.20(1H,d,J=BHz), 8.47-8.54(lH,m),10.10-10.50(lH,m). 15 Preparation Example 120 According to the same manner as that of Preparation Example 72 except that 2-[3-bromo-l-(3-chloro-2-pyridinyl) 1H-pyrazole-5-yl]-8-bromo-6-fluoro-4H-3,1-benzoxazine-4-one was used in place of 2-[3-bromo-l-(3-chloro-2-pyridinyl) 20 1H-pyrazole-5-yl)-8-chloro-4H-3,1-benzoxazine-4-one to obtain the present compound (120) of the formula: .386 Br Br F N N H (120) CI'N H - NN OCH3 CI ON H N H O The present compound (120) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):3.42-3.69(3H,m),7.34(1H,d,J= 8 Hz), 7.41(1H,s),7.60(1H,dd,J=8Hz,5Hz),7.89(lH,d,J=8Hz),8.16(1H, 5 d,J=8Hz),8.50(1H,d,J=5Hz),9.36(lH,brs),10.18(lH,brs),10.42 (lH,brs). Preparation Example 121 According to the same manner as that of Preparation Example 72 except that 2-[3-bromo-l-(3-chloro-2-pyridinyl) 10 1H-pyrazole-5-yl]-8-phenyl-4H-3, 1-benzoxazine-4-one was used in place of 2-[3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole 5-yl) -8-chloro-4H-3, 1-benzoxazine-4-one to obtain the present compound (121) of the formula: Br O N N H H ? -N

OCH

3 C0 N T N H 0 15 The present compound (121) H-NMR(DMSO-d 6 ,TMS)5(ppm):3.49-3.68(3H,m),7.2 4

-

7

.

67 (10H,m), 387 8.08(1H,d,J=8Hz),8.43(1H,d,J=4Hz),9.29(lH,brs),10.08(lH, brs),10.19(lH,brs). Preparation Example 122 A mixture of 0.17g of 5 6,8-dibromo-2-[4-bromo-1-(3-chloro-2-pyridinyl)-lH-pyrrol-2 -yl]-4H-3,1-benzoxazine-4-one, 0.27g of methyl carbazate and 20ml of N,N-dimethylformamide was stirred at room temperature for 2 days. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer 10 was washed with water, dried over sodium sulfate, and concentrated under reduced pressure to obtain 0.15g of the present compound (122) of the formula: Br Br Br O N N H (122) N H .... N

OCH

3 CI N 0 N r H 0 The present compound (122) 15 1H-NMR(DMSO-d 6 )5(ppm):3.67(3H,s),7.36(lH,s), 7

.

46 (1H,d, J=2Hz),7.54(lH,dd,J=8Hz,5Hz),7.70(1H,s),8.09(1H,d,J= 8 Hz), 8.13(1H,d,J=2Hz),8.48(lH,d,J=5Hz),9.40(1H,brs), 9

.

97 (1H,brs),10.18 (1H,brs) Preparation Example 123 20 According to the same manner as that of Preparation Example 122 except that 8-bromo-2-[4-bromo-1-(3-chloro-2- ,388 pyridinyl)-1H-pyrrol-2-yl]-6-chloro-4H-3,1-benzoxazine- 4 one was used in place of 6, 8-dibromo-2- [4-bromo-l- (3-chloro-2 pyridinyl)-lH-pyrrol-2-yl]-4H-3,1-benzoxazine-4-one to obtain the present compound (123) of the formula: Br C1 Br o / N H (123) N H -N

OCH

3 C1 N O N H O 5 The present compound (123) H-NMR(DMSO-d)(ppm):3.62(3H,s),7.30(1H,s), 7

.

39 (lH,d, J=2Hz),7.48(lH,dd,J=8Hz,5Hz),7.52(lH,s),7.96(1H,d,J= 2 Hz), 8.03(1H,dd,J=BHz,2Hz),8.42(lH,dd,J=5Hz,2Hz),9.35(lH,brs), 10 9.92(1H,brs),10.11(1H,brs) Preparation Example 124 According to the same manner as that of Preparation Example 122 except that 2-[4-bromo-1-(3-chloro-2-pyridinyl) 1H-pyrrol-2-yl)-6-cyano-8-methyl-4H-3,1-benzoxazine-4-one 15 was used in place of 6,8-dibromo-2-[4-bromo-1-(3-chloro-2 pyridinyl)-H-pyrrole-2-yl]- 4

H-

3 ,1-benzoxazine-4-one to obtain the present compound (124) of the formula: 389 Br H 3 C CN Br0 / NA N H (124) H -N OCH 3 C0 0 N N H O The present compound (124) 'H-NMR(DMSO-d 6 )5(ppm):2.21(3H,s),3.64( 3 H,s), 7

.

2 5(lH,d, J=2Hz),7.41(1H,d,J=2Hz),7.49(lH,dd,J=8Hz,5Hz), 7

.

77 (lH,s), 5 7.88(1H,s),8.04(lH,dd,J=BHz,2Hz),8.43(lH,dd,J=5Hz,2Hz), 9.36(lH,brs),10.05(1H,brs),10.27(1H,brs) Preparation Example 125 According to the same manner as that of Preparation Example 72, 2- [3-bromo-l- (3-chloro-2-pyridinyl) -1H-pyrazol 10 5-yl]-8- ethyl-4H-3,1-benzoxazine-4-one was used in place of 2-[3-bromo-l-(3-chloro-2-pyridinyl) -1H-pyrazol-5-yl]-8 chloro-4H-3,1-benzoxazine-4-one to obtain the present compound (125) of the formula:

CH

3

CH

2 Br / N/ N 'N H (125) H ? -N OCH3 N H 0 15 The present compound (125) 1 H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 1.06-1.13 (3H, m), 2.45-2.60 (2H, m), 3.55-3.70 (3H, in), 7.25-7.47 (4H, m), 7.57-7.63 (1H, m), -390 8.14-8.19 (1H, m), 8.46-8.53 (1H, m), 9.24 (1H, brs), 9.98 (1H, brs), 10.16 (1H, brs). Preparation Example 126 According to the same manner as that of Preparation 5 Example 5, N-[4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl) -1-cyclohexyl-3-trifluoromethyl-1H-pyrazole-5-carboxamide was used in place of N-[4-chloro-2-(hydrazinocarbonyl)-6 methylphenyl] -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl-1H -pyrazole-5-carboxamide to obtain the present compound (126) 10 of the formula:

H

3 C

F

3 C O CI N N H (126) N H Y ....N OCH3 0 N H The present compound (126) 1 i-NMR (DMSO-d 6 ) 6 (ppm): 1.20-1.41 (3H, m), 1.67-1.80 (5H, m), 1.98-2.00 (2H, m), 2.25 (3H, s), 3.56 (3H, s), 5.00-5.08 (1H, 15 m), 7.33 (1H, s), 7.40 (1H, d, J=2Hz), 7.55 (1H, d, J=2Hz), 9.02 (1H, brs), 9.94 (1H, brs), 10.04 (1H, brs). Preparation Example 127 According to the same manner as that of Preparation Example 93, 4, 5-dibromo-N- [4-chloro-2- (hydrazinocarbonyl) 20 6-methylphenyl] -1- (3-chloro-2-pyridinyl) -1H-pyrrole-2 carboxamide was used in place of 4-bromo-N-[4-chloro-2- ,391 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyridinyl )-1H-pyrrole-2-carboxamide to obtain the present compound (127) of the formula: Br

H

3 C CI 0 B Br N N H (127) N H N

OCH

3 C1 0 N N H 5 The present compound (127) 'H-NMR (DMSO-d 6 ) 5 (ppm): 2.09 (3H, s), 3.63 (3H, s), 7.36 (1H, s), 7..42 (1H, s), 7.49 (1H, s), 7.57 (1H, dd, J=8Hz, 5Hz), 8.14 (1H, d, J=8Hz), 8.50 (1H, d, J=5Hz), 9.29 (1H, brs), 9.79 (1H, brs), 10.12 (1H, brs). 10 Preparation Example 128 A mixture of 0.20 g of 4,5-dibromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl]-1- (3-chloro-2-pyridinyl )-1H-pyrrole-2-carboxamide, 0.04 g of N,N-dimethylcarbamoyl chloride and 0.08 ml of pyridine in N,N-dimethylformamide was 15 stirred at room temperature for 14 hours. Water was poured into the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column 20 chromatography to obtain 0.16 g of the present compound (128) of the formula: 392 Br H 3 C CI 0 B1 Br N N H (128) N H O N-N

N(CH

3

)

2 N H 0 The present compound (128) 1 H-NMR (DMSO-d 6 ) 5 (ppm): 2.08 (3H, s), 2.88 (6H, s), 7.40 (1H, d, J=2Hz), 7.44 (1H, d, J=2Hz), 7.52 (1H, s), 7.58 (1H, dd, J=8Hz, 5 5Hz), 8.14 (1H, dd, J=8Hz, 1Hz), 8.50 (1H, dd, J=5Hz, 1Hz), 8.56 (1H, brs), 9.75 (1H, brs), 9.81 (1H, brs). Preparation Example 129 According to the same manner as that of Preparation Example 122, 2- [5-chloro-1- (3-chloro-2-pyridinyl) -1H-pyrrol 10 2-yl] -6-chloro-8-methyl-4H-3, 1-benzoxazine-4-one was used in place of 6,8-dibromo-2-[4-bromo-1- (3-chloro-2-pyridinyl) -1H pyrrol-2-yl]-4H-3,1-benzoxazine-4-one to obtain the present compound (129) of the formula:

H

3 C Ci 0 / C1 N H (129) N H -N

OCH

3 CI 0 N N H 0 15 The present compound (129) H-NMR(DMSO-d 6 ,TMS)5(ppm):2.11(3H,s),3.63(3H,s),6.

4 8(lH,d, J=4Hz),7.24(1H,d,J=4Hz),7.48(1H,s),7.55(lH,dd,J=8Hz,5Hz), 7.95(1H,s),8.12(1H,dd,J=8Hz,2Hz),8.49(1H,dd,J=5Hz,2Hz),9.31 393 (lH,brs),9.74(lH,brs),10.13(1H,brs) Preparation Example 130 According to the same manner as that of Preparation Example 93, N-[4-chloro-2-(hydrazinocarbonyl)-6 5 methylphenyl)-1-(3-chloro-2-pyridinyl)-lH-pyrrole-2 carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyrldinyl )-1H-pyrrole-2- carboxamide to obtain the present compound (130) of the formula:

H

3 C CI 0 N H (130) N H -N OCH3 C0 N N HO H 0 10 The present compound (130) H-NMR(DMSO-d6,TMS)8(ppm):2.16(3H,s),3.61(3H,s),6.

37 (lH,d, J=3Hz),7.12-7.18(2H,m),7.40(1H,s),7.45-7.50(2H,m),8.03(1H, d,J=8Hz),8.42(lH,d,J=5Hz),9.33(lH,brs),9.71(lH,brs),10.14 15 (1H,brs) Preparation Example 131 According to the same manner as that of Preparation Example 10, 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2 (hydrazinocarbonyl)-6-methylphenyl]-1H-pyrazole-5 20 carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl)-1-(3-chloro-2 pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carboxamide to 394 obtain the present compound (131) of the formula:

H

3 C CN Br\ 0 NN Ny H (131 H N N(CH 3

)

2 N H O The present compound (131) 1H-NMR(DMSO-d ,TMS)6(ppm) :2.18 (3H,s) ,2.88 (6H,s) ,7 .49 (lH,s), 5 7.62(lH,dd,J=BHz,5Hz),7.82(1H,s),7.93(lH,s),8.19(1H,dd, J=BHz,1Hz),8.50(1H,dd,J=5Hz,1Hz),8.63(1H,brs), 9

.

93 (lH,brs), 10. 42,(1E, brs) Preparation Example 132 According to the same manner as that of Preparation 10 Example 93, 4, 5-dichloro-N- (4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2-pyridinyl) -1H-pyrrole-2 carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2 pyridinyl)-1H-pyrrole-2-carboxamide to obtain the present 15 compound (132) of the formula: NH3C C CI N H H (132) c0 -N OCH0 N H 0 The present compound (132) H-NMR(DMSO-d,TMS)6(ppm):2.10(3H,s),3.63( 3 H,s), 7

.

39

(

2 H,s), -395 7.49(lH,s),7.59(1H,dd,J=8HZ,5HZ),8.15(1H,dd,J=8HZ,1Hz), 8 .51 (lH,dd,J=5Hz,1Hz),9.30(lH,brs),9.82(lH,brs),10.1 2 (lH,brs) Preparation Example 133 According to the same manner as that of Preparation 5 Example 128, 4, 5-dichloro-N- [4-chloro-2- (hydrazinocarbonyl) 6-methylphenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2 carboxamide was used in place of 4,5-dibromo-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2 pyridinyl)-lH-pyrrole-2-carboxamide to obtain the present 10 compound (133) of the formula:

H

3 C C1 C N N H (133) H -N

N(CH

3

)

2 CI 0 N N H o The present compound (133) 'H-NMR(DMSO-d6,TMS)6(ppm):2.10(3H,s),2.53(6H,s),7.37- 7

.

39 (2H,m),7.51(1H,d,J=2Hz),7.59(1H,dd,J=8Hz,5Hz),8.17(lH,dd, 15 J=8Hz,2Hz),8.52(1H,dd,J=5Hz,2Hz),9.31(1H,brs),9.82(1H,brs), 10.13(lH,brs) Preparation Example 134 A mixture of 0.50 g of 4-bromo-N-[4-chloro-2 (N-methylhydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2 20 pyridinyl)-1H-pyrrole-2-carboxamide, 0.11 g of methyl chloroformate, 0.18 ml of pyridine and 5 ml of N,N-dimethylformamide was stirred at room temperature for 3 ,396 hours. The reaction mixture was poured into water, and extracted with ethyl acetate three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous 5 sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.09 g of the present compound (134) of the formula: Br H 3 C CI N H (134) N H -N

OCH

3

H

3 C 0 10 The present compound (134) 1H-NMR(CDCl 3 ,TMS)6(ppm):2.05-2.12(3H,m),3.21( 3 H,S),3.

54 3 .76(3H,m),7.02(1H,d,J=2Hz),7.06(2H,s),7.29(lH,brs), 7

.

33 (lH,dd,J=8Hz,5Hz),7.80-7.86(2H,m),8.40 (lH,dd, J=5Hz,2Hz), 8.99(lH,brs) 15 Preparation Example 135 According to the same manner as that of Preparation Example 72, 2- [3-bromo-l- (3-chloro-2-pyridinyl) -lH-pyrazol 5-yl] -6, 8-dichloro-4H-3, 1-benzoxazine-4-one was used in place of 2-[3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazol-5 20 yl]-8-chloro-4H-3,1-benzoxazine-4-one to obtain the present compound (135) of the formula: .397 CI CI Br O N'N H (135) H -N OCH 3 CI i'N H o The present compound (135) 'H-NMR(DMSO-d 6 ,TMS)6(ppm):3.47-3.62(3H,m), 7

.

4 0(1H,s), 7.51(lH,s),7.60(lH,dd,J=8Hz,5Hz),7.93(lH,s),8.16(lH,dd, 5 J=8Hz,lHz),8.50(1H,dd,J=5Hz,lHz),9.37(H,brs), 10.24(1H,brs),10.48(lH,brs) Preparation Example 136 A mixture of 0.25 g of 4-bromo-N-[4-chloro-2-(N methylhydrazinocarbonyl)-6-methylphenyll-1-(3-chloro-2 10 pyridinyl)-1H-pyrrole- 2 - carboxamide, 0.06 g of N,N-dimethylcarbamoyl chloride, 0.09 ml of pyridine and 5 ml of N,N-dimethylformamide was stirred at 70"C for 8 hours. The reaction mixture was poured into water, and a deposited precipitate was collected by filtration. The resulting solid 15 was washed with acetonitrile to obtain 0.10 g of the present compound (136) of the formula: Br H 3 C C1 Br O N NH N (136) tN H -N N(CH3)2 CI 0 N

H

3 C 0 The present compound (136) 'H-NMR(DMSO-d,,TMS)6(ppm):2.l1(3H,s),2.65- 2 .85(6H,m), .398 3.19-3.29(3H,m),7.07(1H,s),7.14(1H,s),7.28 (1H,s), 7.40(1H,s),7.50(lH,dd,J=8Hz,5Hz),7.60(lH,brs),8.06(1H,d, J=8Hz),8.43(lH,d,J=5Hz),9.86(1H,brs) Preparation Example 137 5 Under ice-cooling; 0.50 g of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2-pyridiny1 )-1H-pyrrole-2-carboxamide, 4 ml of formic acid and 2 ml of acetic anhydride were mixed. The mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into 10 water, and extracted with ethyl acetate three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was washed with acetonitrile to obtain 15 0.20 g of the present compound (137) of the formula:

H

3 C CI 0 N H (137) NY H N H CI O N HO The present compound (137) 1H-NMR (DMSO-d 6 ,TMS)5(ppm) :2.15(3H,s),7.

23 (H,s), 7

.

42 -7.

44 (2H,m),7.48-7.52(2H,m),8.05(H,d,J=7Hz),8.43(lH,d,J= 3 Hz), 20 8.98(lH,s),9.76(1H,s),9.96(lH,brs),10.12(1H,brs) Preparation Example 138 ,399 % According to the same manner as that of Preparation Example 115, 3-bromo-1- (3-chloro-2-pyridinyl)

-N

[4-cyano-2- (N-methylhydrazinocarbonyl) -6-methylphenyl) -lH pyrazole-5-carboxamide was used in place of 3-bromo 5 N-[4-chloro-2-(N-methylhydrazinocarbonyl)-6-methylphenyl) 1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide to obtain the present compound (138) of the formula: Br

H

3 C CN 0 N H (138) N H -N

OCH

3 C1,1 O N H 3 C 0 The present compound (138) 10 'H-NMR(DMSO-d,TMS)(ppm):2.21(3H,s),3.08(3Hs),3.45-3.70

(

3 H,m), 7

.

3 0- 7

.

4 3(H,m),7.44-7.61(1H,m),7.63(lH,dd,J=8Hz, 5Hz), 7 .82- 7

.

94 (lH,m),8.21(1H,d,J=8Hz,lHz),8.51(lH,ddJ=5Hz, 1Hz),9.21(1H,brs),10.24(1H,brs) Preparation Example 139 15 According to the same manner as that of Preparation Example 134, 4 -bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2 (N-methylhydrazinocarbonyl)-6-methylphenyl]-1H-pyrrole-2 carboxamide was used in place of 4-bromo-N-[4-chloro-2-(N methylhydrazinocarbonyl) -6-methylphenyl] -l- (3-chloro-2 20 pyridinyl)-1H-pyrrole-2-carboxamide to obtain the present compound (139) of the formula: ,400

H

3 C CN B 0 1 N\ N H (139) N H H N

OCH

3 0 N,

H

3 C 0 The present compound (139) H-NMR(DMSO-ddTMS)(ppm) :2.21(3H,s),3.08( 3 H,s), 3

.

47

-

3

.

7 0 (3H, m) , 7.18-7 .30 (1H, m), 7 .41-7 .50 (1H, m), 7 .51-7 .56 (2H, m) , 5 7.80-7.90(1H,m),8.12(1H,dd,J=8Hz,lHz),8.45(lH,dd,J=5Hz, 1Hz),9.10(1H,brs),9.73(1H,brs) Preparation Example 140 According to the same manner as that of Preparation Example 66, 3-bromo-N- [1-bromo-3- (hydrazinocarbonyl) -2 10 naphthyl) -1- (3-chloro-2-pyridinyl)-1H-pyrazole-5 carboxamide was used in place of N-[1-chloro-3 (hydrazinocarbonyl)-2-naphthyl)-l (3-chloro-2-pyridinyl)-3 trifluoromethyl-1H-pyrazole-5-carboxamide to obtain the present compound (140) of the formula: Br Br O 'N H H (140) H -"N OCH3 CI 0 N H 0 15 The present compound (140) H-NMR(DMSO-d6, TMS) (ppm):3.42-3.71(3H,m),7.4 8 (1H,s), 7 .58 (lH,dd,J=8Hz,5Hz),7.72(1H,t,J=7Hz),7.81(1H,t,J= 7 Hz),8.10- ,401 8.21(3H,m),8.24(1H,d,J=8Hz),8.50(1H,d,J=5Hz),9.34(lH,brs), 10.26(1H,brs),10.64(1H,brs) Preparation Example 141 According to the same manner as that of Preparation 5 Example 66, 4-bromo-N-[1-bromo-3-(hydrazinocarbonyl)- 2 naphthyl)-1-(3-chloro-2-pyridinyl)-lH-pyrrole-2-carboxamide was used in place of N-[l-chloro-3-(hydrazinocarbonyl)-2 naphthyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H pyrazole-5- carboxamide to obtain the present compound (141) 10 of the formula: Br Br N H N H H.N OH (141) CI NN 0 N N H a The present compound (141) 1H-NMR(DMSO-d 6 ,TMS)5(ppm):3.43-3.70(3H,m), 7

.

3 7 (lH,s), 7

.

4 2 7.52(2H,m),7.70(1H,t,J=7Hz),7.79(1H,t,J=7Hz),8.03(H,d, 15 J=7Hz),8.06-8.20(2H,m),8.23(1H,d,J=8Hz),8.43(1H,d,J=4Hz), 9.34(1H,brs),10.09(1H,brs),10.19(1H,brs) Preparation Example 142 According to the same manner as that of Preparation Example 17, 3-bromo--(3-chloro-2-pyridinyl)-N-[4-cyano-2 20 (hydrazinocarbonyl)-6-methylphenyl]-lH-pyrazole-5 carboxamide was used in place of N-[4-chloro-2- .402 (hydrazinocarbonyl)-6-methylphenyl]-l-( 3 -chloro- 2 pyridinyl) -3-trifluoromethyl-1H-pyrazole-5-carboxamide to obtain the present compound (142) of the formula:

H

3 C CN Br\ 0 1" BNO/ 'N N H . (142) H N H CI 0 N' 'f N H 0 5 The present compound (142) 1H-NMR(DMSO-d, TMS) 6 (ppm) :2. 16-2.34 (3H,m) ,7. 35-7. 45 (1H,m) , 7 .57- 7 .66(H,m),7.76-7.88(H,m),7.93-8.02(H,m),8.03-8.12 (lH,m),8.17(1H,d,J=7Hz),8.50(,H,brs),9.55-10.03(lH,m), 10.17-10.58 (2H,m) LO Preparation Example 143 According to the same manner as that of Preparation Example 17, 4-bromo-1- (3-chloro-2-pyridinyl) -N- [4-cyano 2- (hydrazinocarbonyl) -6-methylphenyl] -lH-pyrrole-2 carboxamide was used in place of N-[4-chloro-2 15 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2-pyridinyl )-3-trifluoromethyl-H-pyrazole-5-carboxamide to obtain the present compound (143) of the formula: ,403

H

3 C CN B 0 5 NN H (1 N H N H(13 N H O The present compound (143) 1H-NMR(DMSO-d 6 ,TMS)6(ppm):2.17-2.30 (3H,m), 7

.

24

-

7

.

36 (1H,m), 7.45-7.55(2H,m),7.74-7.82(lH,m),7.88-7.95(1H,m),8.03-8.09 5 (2H,m),8.44(1H,d,J=5Hz),10.02(lH,brs),10.21(lH,brs),10.46 (1H,brs) Preparation Example 144 According to the same manner as that of Preparation Example 119, 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2 10 (N,N' -dimethylhydrazinocarbonyl) -6-methylphenyl]-1H pyrazole-5- carboxamide was used in place of 3-bromo N- [4-chloro-2- (N,N' -dimethylhydra zinocarbonyl) -6 methylphenyl] -1- (3-chloro-2-pyridinyl) -1H-pyrazole-5 carboxamide to obtain the present compound (144) of the 15 formula: Br

H

3 C CN 'N N

CH

3 (144) H - N OCH 3

H

3 C O The present compound (144) H-NMR(DMSO-ds, TMS) 6 (ppm) :2. 14-2.29 (3H,m), 2. 64- 2

.

87

(

3 H,m) , 404 2.87-3.15(3H,m),3.42-3.73(3H,m),7.30-7.45(1H,m),7.54-7.81 (2H,m),7.83-8.01(1H,m),8.15-8.24(1H,m),8.50(lH,brs),10.20 10.68 (1H,m) Preparation Example 145 5 A mixture of 0.25'g of 3-bromo-N-[1-bromo-3 (hydrazinocarbonyl)-2-naphthyl)-1-(3-chloro-2-pyridinyl) 1H-pyrazole-5-carboxamide, 0.22 g of N,N-dimethylcarbamoyl chloride, 4 ml of acetonitrile and 1 ml of pyridine was stirred at room temperature for 2 hours, and allowed to stand at room 10 temperature overnight. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under 15 reduced pressure to obtain 0.20 g of the present compound (145) of the formula: Br\ 0 Br NNH NN N H (145) H -N

N(CH

3

)

2 N H o The present compound (145) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.88(6H,s),7.54(1H,s), 7 .5 9 (1H,dd, 20 J=8Hz,5Hz),7.72(1H,t,J=7Hz),7.79(1H,t,J=7Hz),8.0 9 (lH,d, J=7Hz),8.15(1H,dd,J=8Hz,1Hz),8.19-8.26(2H,m),8.50(1H,dd, -405 J=5, 1Hz) ,8.54 (lH,brs) ,9.90 (1H,brs) ,10.57 (lH,brs) Preparation Example 146 According to the same manner as that of Preparation Example 145, 4-bromo-N- [1-bromo-3- (hydrazinocarbonyl) 5 2-naphthyl]-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2 carboxamide was used in place of 3-bromo-N-[1-bromo-3 (hydrazinocarbonyl) -2-naphthyll -1- (3-chloro-2-pyridinyl) -lH -pyrazole-5- carboxamide to obtain the present compound (146) of the formula: Br NN H '(146) N H N N(CH 3

)

2 0 N 'r 10 The present compound (146) 'H -NMR(DMSO.- d,, TMS)5(ppm):2.88 (6H, s), 7

.

37

-

7

.

4 4 (lH,m), 7.44-7.51(2H,m),7.69(1H,t, J=7Hz),7.77(lH, t, J=7Hz),8.01-8.10 (2H,m),8.19-8.25(2H,m),8.43(1H,dd,J=5Hz,1Hz),8.55(lH,brs), 15 9.84(1H,brs),10.05(1H,brs) Preparation Example 147 A mixture of 0.26 g of 4-bromo-N-[4-chloro-2-(N,N' dimethylhydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2 pyridinyl)-1H-pyrrole-2- carboxamide, 0.05 g of methyl 20 chloroformate, 0.09 ml of pyridine and 5 ml of N,N-dimethylformamide was stirred at room temperature for 3 .406 hours. The reaction mixture was poured into water, and extracted with ethyl acetate three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous 5 sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.20 g of the present compound (147) of the formula:

H

3 C CI Br O / N

CH

3 (147) H , N OCH3 C N OT

H

3 C 0 10 The present compound (147) 1H-NMR(CDC 3 ,TMS)(ppm):2.18(3H,s), 2

.

8 8- 2

.

9 8( 3 H,m), 3 .13-3.22(3H,m),3.63-3.82(3H,m),7.01-7.12(3H,m), 7 .20(lH,s), 7.30(1H,d,J=5Hz),7.79-7.80(lH,m),8.37-8.

38 (lH,m), 8.45-8.58 (1H,brm) 15 Preparation Example 148 According to the same manner as that of Preparation Example 93, N-[4,6-dibromo-2-(hydrazinocarbonyl)phenyl] 4, 5-dichloro-1- (3-chloro-2-pyridinyl) -lH-pyrrole-2 carboxamide was used in place of 4-bromo-N-[4-chloro-2 20 (hydrazinocarbonyl) -6-methylphenyl] -l- (3-chloro-2 pyridinyl)-lH-pyrrole-2-carboxamide to obtain the present compound (148) of the formula: 407 Br Br CI O N H (148) N H -N

OCH

3 CI 0 N N H 0 The present compound (148) H-NMR(DMSO-d 6 ,TMS)6(ppm):3.62(3H,s),7.45(1H,s), 7

.

58 (lH,dd, J=8Hz,5Hz),7.63(1H,s),8.10(lH,s),8.15(H,dd,J=8Hz, 2 Hz), 8 .51 5 (lH,dd,J=5Hz,2Hz),9.34(1H,brs),10.00(lH,brs),10.15(lHbrs) Preparation Example 149 A mixture of 0.50 g of 3-bromo-N-[4-chloro-2-(N methylhydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro-2 pyridinyl)-1H-pyrazole-5- carboxamide, 0.09 g of acetyl 10 chloride, 0.09 g of pyridine and 10 ml of tetrahydrofuran was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced 15 pressure. The resulting residue was washed with methylt-butyl ether and hexane to obtain 0.48 g of the present compound (149) of the formula:

H

3 C C1 Br, 0 7 N N H N N H (149) C0 H N CH3 N

CH

3

O

408 The present compound (149) 'H-NMR(CDCl 3 ,TMS)5(ppm):1.56(3H,s),2.01(3H,s), 3

.

2 4

(

3 H,s), 6.97(2H,d,J=2Hz),7.39-7.42(2H,m),7.88(1H,dd,J=8Hz,1Hz), 8.39(1H,s),8.47(1H,dd,J=5Hz,1Hz),10.12(1H,brs) 5 Preparation Example 150 A mixture of 0.50 g of 3-bromo-N-[4-chloro-2 (N-methylhydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2 pyridinyl)-1H-pyrazole-5-carboxamide, 0.12 g of methyl chlorothiol formate, 0.09 g of pyridine and 10 ml of 10 tetrahydrofuran was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was 15 washed with methyl t-butyl ether and hexane to obtain 0.50 g of the present compound (150) of the formula: Br H 3 C Ci 0 N'N, N H (150) H N

SCH

3 C' IN O Y

CH

3 0 The present compound (150) 'H-NMR(CDCl 3 ,TMS)5 (ppm) :2.06(3H,brs) ,2.25 (3H,brs) , 3

.

2 0 ( 3 H, 20 brs),6.99-7.29(3H,m),7.41(lH,dd,J=8Hz,5Hz),7.88(lH,dd, J=8Hz,1Hz),8.01-8.23(1H,brm),8.46(lH,d,J=5Hz),9.

49

-

9

.

79 (1H, 409 brm) Preparation Example 151 A mixture of 0.49 g of 2-[3-bromo-1-(3-chloro-2 pyridinyl)-1H-pyrazol-5-yl]-10-chloro-4H-naphtho[ 2 ,3-d] [1,3' 5 ]oxazine-4-one, 0.90 g of methyl carbazate and 5 ml of N,N-dimethylformamide was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed successively with water 10 and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 0.31 g of the present compound (151) of the formula: CI Br O / N H H N'N H H CH (151) H ,N OCH3 C N 0 N r N H 0 15 The present compound (151) 1H-NMR(DMSO-d,TMS)(ppm):3.59-3.68( 3 H,m), 7

.

47 (1H,s), 7 .56-7.62(lH,m),7.74(H,d,J=7Hz),7.80(1H,d,J=7Hz), 8 .12-8.18 (3H,m),8.25(lH,d,J=7Hz),8.50(lH,d,J=5Hz),9.35(1H,brs),10.

3 0 (1H,brs),10.60(1H,brs) 20 Preparation Example 152 According to the same manner as that of Preparation 410 Example 151, 2-[4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrol 2-yl]-10- chloro-4H-naphtho[2,3-d] [1,3] oxazine-4-one was used in place of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H pyrazol-5-yl)-10-chloro-4H-naphtho[ 2 ,3-d] [1,3]oxazine-4-one' 5 to obtain the present compound (152) of the formula: Br\ CI N N H (152) ClH 0 N NyOCH3 N H O The present compound (152) H-NMR(DMSO-d 6 ,TMS)5(ppm):3.55-3.70(3H,m),7.35(1H,s), 7

.

4 3 7 .51( 2 H,m),7.71(1H,t,J=8Hz),7.79(1H,t,J=8Hz),8.04(1H,d, 10 J=8Hz),8.12(2H,d,J=8Hz),8.23(1H,d,J=BHz),8.43(1H,d,J=5Hz), 9.35(lH,brs),10.06(1H,brs),10.24(1H,brs) Preparation Example 153 According to the same manner as that of Preparation Example 93, 4-chloro-N-[4-chloro-2-(hydrazinocarbonyl) 15 6-methylphenyl) -1- (3-chloro-2-pyridinyl) ) -1H-pyrrole-2 carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2-pyridinyl )-1H-pyrrole-2-carboxamide to obtain the present compound (153) of the formula: .411

H

3 C C1 N H (153) NN Cj'tH -N OCH3 'N H 6 The present compound (153) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.17(3H,s),3.63(3H,s), 7 .1 8 (lH,d, J=2Hz),7.35(1H,d,J=2Hz),7.39(lH,s),7.47(1H,s),7.49(1H,dd, 5 J=8Hz,5Hz),8.03(H,dd,J=8Hz,2Hz),8.42(1H,dd,J=5Hz,2Hz), 9.31(1H,brs),9.76(1H,brs),10.12(1H,brs) Preparation Example 154 A mixture of 0.52 g of 3-bromo-N-[4,6-dichloro-2 (N-methylhydrazinocarbonyl)phenyl] -1- (3-chloro-2-pyridinyl) 10 -1H-pyrazole-5-carboxamide, 0.10 g of methyl chloroformate, 0.09 g of pyridine and 7 ml of tetrahydrofuran was stirred at room temperature for 1 hour. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous 15 magnesium sulfate, and concentrated under reduced pressure. The resulting residue was washed with methyl t-butyl ether and hexane to obtain 0.49 g of the present compound (154) of the formula: CI CI N, N H (154) N H - .N OCHa C N N C 1H 3 C O .412 The present compound (154) 'H-NMR(CDC1 3 ,TMS)5(ppm) :3.12-3.18(3H,brm),3.60-3.84(3H,brm), 7.21-7.22(2H,m),7.34(1H,brs),7.41(1H,dd,J=8Hz,5Hz), 7.51(lH,brs),7.88(lH,dd,J=8Hz,lHz),8.48(lH,dd,J=5Hz,1Hz), 5 9.85(lH,brs) Preparation Example 155 According to the same manner as that of Preparation Example 154, ethyl chloroformate was used in place of methyl chloroformate to obtain the present compound (155) of the 10 formula: CI C1 N H N'N H '(155) N H -. "N

OCH

2

CH

3 CI 0 N

H

3 C 0 The present compound (155) H -NMR (C DCl13, TMS) 5 (ppm) : 1. 11 -1. 3 9 (3 H, m) , 3. 12 -3. 18 (3 H, b rm) , 4 .06-4.25(2H,brm),7.08-7.22(2H,m),7.34(1H,brs),7.41(1H,dd, 15 J=8Hz,5Hz),7.43(1H,brs),7.88(1H,dd,J=8Hz,1Hz),8.49(1H,dd, J=5Hz,1Hz),9.87(1H,brs) Preparation Example 156 A mixture of 0.50 g of 3-bromo-N-(4-chloro-2-(N-methylhydrazinocarbonyl)-6 20 methylphenyl] -1- (3-chloro-2-pyridinyl) -1H-pyrazole-5 carboxamide and 5 ml of formic acid was stirred at 50*C for 1 hour. Water was poured into the reaction mixture, and the .413 mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was washed with t-butyl ether and hexane to obtain 0.40 g of' 5 the present compound (156) of the formula:

H

3 C Br O / CI N'N N H (156) N H N H ..N IrH (16 C " N OH 3 O CH3 0 The present compound (156) 1H-NMR(CDCl 3 ,TMS)6(ppm):2.02(3H,s),3.25(3H,s), 6

.

9 9

(

2 H,d, J-4Hz),7.35(lH,s),7.41(1H,dd,J=8Hz,5Hz),7.64(lH,s), 7 .88(lH, 10 dd,J=8Hz,2Hz),8.47(lH,dd,J=5Hz,2Hz),8.58(lH,s),10.08(lH,s) Preparation Example 157 According to the same manner as that of Preparation Example 93, 5-bromo-N- [4-chloro-2- (hydrazinocarbonyl) 6-methylphenyll -1- (3-chloro-2-pyridinyl) -1H-pyrrole-2 15 carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro-2-pyridinyl )-lH-pyrrole-2- carboxamide to obtain the present compound (157)of the formula: A 14

H

3 C CI Br N H (157) Br N ; H N OCH 3 Ci O N N H 0 The present compound 157 1H-NMR (DMSO-dr, ,TMS) 5(ppm) :2.11 (3H,s ) ,3. 63(3H, s),6. 54 (1H, d, J=3Hz),7.24(1H,d,J=3Hz),7.39(1H,s),7.46(1H,s),7.54(lH,dd, 5 J=8Hz,4Hz),8.09(1H,d,J=BHz),8.28(1H,d,J=4Hz),9.

3 0(lH,brs), 9.74(1H,brs),l0.13(1H,brs) Preparation Example 158 Under ice-cooling, 0.14 ml of methyl chloroformate was added to a mixture of 0.50 g of the present compound (93), 0.26 10 ml of triethylamine and 15 ml of tetrahydrofuran. The mixture was stirred at room temperature for 5 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium 15 chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.21 g of the present compound (158) of the formula: .415

H

3 C C1 N H _-OCH, (158) C1 OQ N-N IN H OCHs The present compound (158) 'H-NMR(CDC1 3 ,TMS)6(ppm):2.22(3H,s),3.79(6H,s), 7 .01(lH,d, J=2Hz),7.07(1H,d,J=2Hz),7.30(1H,dd,J=8Hz,5Hz),7.32(lH,s), 5 7.39(lH,s),7.82(1H,d,J=8Hz),8.33(1H,d,J=5Hz),8.45(1H,brs), 8.88 (1H, brs) Preparation Example 159 According to the same manner as that of Preparation Example (158), the present compound (153) was used in place of 10 the present compound (93) to obtain the present compound (159) of the formula: C1 H3C CI 00 H _ 0CH 3 (159) CI O N-N N H _ The present compound (159) 'H-NMR(CDC1 3 ,TMS)5(ppm):2.18(3H,s),3.

7 3

(

6 H,s), 7 .00- 7 .01 15 (2H,m),7.24-7.28(3H,m),7.79(lH,d,J=8Hz),8.29(1H,d,J=4Hz), 8.82(1H,brs),9.06(1H,brs) Preparation Example 160 Under ice-cooling, 0.50 g of 3-bromo-N-[4-chloro-2-(N methylhydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro-2- 416 pyridinyl)-1H-pyrazole-5-carboxamide, 0.12 g of N,N-dimethylcarbamoyl chloride, 0.09 g of pyridine and 20 ml of tetrahydrofuran were mixed, and the mixture was stirred at 50 0 C for 14 hours. To the mixture were further added 0.12 g' 5 of N,N-dimethylcarbamoyl chloride and 0.09 g of pyridine. The mixture was stirred at 50*C for 9 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced 10 pressure. The resulting residue was washed with methyl t-butyl ether, and hexane to obtain 0.15 g of the present compound (160) of the formula:

H

3 C Cl N'N N H (160) N'N H H -N N(CH 3

)

2 C1 0 N ' "NIY

CH

3 O The present compound (160) 15 H-NMR(CDCl 3 ,TMS)5(ppm):1.98(3H,s),2.46(6H,s), 3 .30( 3 H,s), 6 .95(lH,d,J=2Hz),7.05(1H,d,J=2Hz),7.37(lH,dd,J=8Hz,5Hz), 7 .51(lH,s),7.81(lH,s),7.85(1H,dd,J=8Hz,2Hz),8.45(1H,dd, J=5Hz,2Hz),10.34(1H,brs). Preparation Example 161 20 According to the same manner as that of Preparation Example 93, 5-bromo-N-[4-chloro-2-(hydrazinocarbonyl)- A17 6-methylphenyl]-1-(2-pyrimidinyl)-1H-pyrrole-2-carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro-2-pyridinyl )-1H-pyrrole-2- carboxamide to obtain the present compound 5 (161) of the formula:

H

3 C 0 -' Br f3N H(1) H N

OCH

3 NNN, 0 N H N The present compound (161) 1H-NMR(DMSO-d 6 ,TMS)5(ppm) :2.14 (3H,s) , 3

.

46

-

3

.

67

(

3 H,m), 6.08-6.50(1H,m),7.08-7.29(1H,m),7.38(1H,s),7.51(1H,s), 10 7.58-7.65(1H,m),8.89-8.95(2H,m),9.09-9.39(1H,m), 9.74-9.90(1H,m),10.11(1H,brs) Preparation Example 162 According to the same manner as that of Preparation Example 93, 4-bromo-N- [4-chloro-2- (hydrazinocarbonyl) 15 6-methylphenyl]-1-(2,6-dichlorophenyl)-1H-pyrrole-2 carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyridinyl )-1H-pyrrole-2- carboxamide to obtain the present compound (162) of the formula: ,418

H

3 C Br O /. CI N N H (162) N H -N

OCH

3 CI ~CI O N H O The present compound (162) 1 H-NMR(DMSO-d 6 ,TMS)6(ppm) :2.11(3H,s),3.46- 3

.

6 8

(

3 H,m) , 7.27(lH,s),7.30-7.47(3H,m),7.50(lH,s),7.53-7.65(2H,m), 5 9.02-9.38(1H,m),9.71(1H,brs),10.13(1H,brs) Preparation Example 163 According to the same manner as that of Preparation Example 93, 4-bromo-N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl] -1- (3, 5-dichloro-4-pyridinyl) -lH-pyrrole-2 10 carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl]-1- (3-chloro-2-pyrldinyl )-lH-pyrrole-2- carboxamide to obtain the present compound (163) of the formula: Br

H

3 C CI N N H (163) N H N H -N OCH 3 Ci ~CI O N H O N 15 The present compound (163) 'H-NMR(DMSO-d 6 ,TMS)6(ppm)):2.12(3H,s),3.

4 8-3.6 7

(

3 H,m), 7.33-7.40(2H,m),7.46(lH,d,J=2Hz),7.51(1H,d,J=2Hz), .419 8.76(2H,s),9.31(lH,brs),9.82(lH,brs),10.14(lH,brs) Preparation Example 164 According to the same manner as that of Preparation Example 137, 4, 5-dichloro-N-[4-chloro-2- (hydrazinocarbonyl) 5 6-methylphenyl] -1- (3-chloro-2-pyridinyl) -1H-pyrrole-2 carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro-2-pyridinyl )-lH-pyrrole-2-carboxamide to obtain the present compound (164)of the formula: C1

H

3 C CI CI NN H (164) H N HO 10 The present compound (164) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.09-2.19(3H,s),7.34-7.53(3H,m), 7.59(lH,dd,J=8Hz,5Hz),8.06(lH,s),8.16(lH,d,J=8Hz), 8.52(lH,d,J=5Hz),9.87(lH,brs),10.13(lH,brs)10.38(lH,brs) 15 Preparation Example 165 Under ice-cooling, 0.43 g of N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (2, 6-dichlorophenyl) 1H-pyrrole-3-carboxamide, 0.15 g of methyl chloroformate, 2 ml of pyridine and 10 ml of acetonitrile were mixed, and the 20 mixture was stirred for 1 hour under ice-cooling. Water was poured into a reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were ,420 combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 0.16 g of the present compound (165) of the formula:'

H

3 C Ci 0 N H (165) C N 1 H -N OCH 3 O N ,Y CIH 0 The present compound (165) 'H-NMR (DMSO-d 6 , TMS) 6 (ppm) :2. 24 (3H, s) , 3. 38-3. 65 (3H, m) , 6.81(lH,brs),6.96(1H,brs),7.33-7.61(4H,m),7.

6 8- 7

.

74

(

2 H,m), 9.37(1H,brs),9.52(lH,brs),10..21(lH,brs) 10 Preparation Example 166 A mixture of 0.56 g of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-lH-pyrazol-5-yl]-6,8 dibromo-4H-3,1-benzoxazine-4-one, 0.47 g of 2,4,4-trimethylsemicarbazide and 15 ml of 15 1-methyl-2-pyrrolidone was stirred at room temperature for 22 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue 20 was washed with ethyl acetate to obtain 0.11 g of the present compound (166) of the formula: ,421 BBr Br NNA N CH3(16 N N N(CH 3

)

2 Cl,, 0 N ' ) I N H 0 The present compound (166) 1 H-NMR (DMSO-d 6 , TMS) 6 (ppm) :2. 66 (6H, s) ,2. 68

(

3 H, s) , 7.45(1H,brs),7.59-7.63(2H,m),8.15-8.17(2H,m), 5 8.49(1H,d,J=4Hz), 10.50(lH,brs),10.55(1H,brs). Preparation Example 167 According to the same manner as that of Preparation Example 158, the present compound (132) was used in place of the present compound (93) to obtain the present compound (167) 10 of the formula:

H

3 C C1 NC CI N N

-OCH

3 (167) C N 0 N-N I 1N H 0 OCH3 The present compound (167) lH-NMR(CDC1 3 ,TMS)5(ppm):2.18(3H,s),3.82(6H,s),7.00(lH,s), 7.32(1H,d,J=2Hz),7.36-7.39(2H,m),7.86(1H,dd,J=8Hz,2Hz), 15 8.12(1H,s),8.43(1H,dd,J=5Hz,2Hz),8.85(1H,brs) Preparation Example 168 According to the same manner as that of Preparation Example 134, 4,5-dichloro-N-[4-chloro-2-(N- .422 methylhydrazinocarbonyl)-6-methylphenyl)-1-(3-chloro-2 pyridinyl)-1H-pyrrole- 2 - carboxamide was used in place of 4-bromo-N-[4-chloro-2-(N-methylhydrazinocarbonyl)-6 methylphenyl]-1-(3-chloro-2-pyridinyl)-lH-pyrrole-2 5 carboxamide to obtain the present compound (168) of the formula:

H

3 C C1 CI N N H (168) H -N

OCH

3 CI 0 N

H

3 C 0 The present compound (168) 'H.-NMR(CDCl 3 ,TMS)5(ppm):2.02-2.11(3H,m), 3 .02- 3

.

28

(

3 H,m), 10 3.54-3.89(3H,m),6.95-7.15(1H,m),7.22-7.31(2H,m),7.39(lH,dd, J=8Hz,5Hz),7.70(1H,brs),7.87(lH,dd,J=8Hz,2Hz),8.47(lH,dd, J=5Hz,2Hz),9.23(lH,brs) Preparation Example 169 According to the same manner as that of Preparation 15 Example 5, N-(4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl] -1-[(2-fluoro-3-pyridinyl)methyl)-3-trifluoromethyl-1H pyrazole-5- carboxamide was used in place of N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyridinyl )-3-trifluoromethyl-1H-pyrazole-5-carboxamide to obtain the 20 present compound (169) of the formula: .423

H

3 C CI F3C 0 N N F H H 3 (169) N CH 2 O N 0 The present compound (169) H-NMR (DMSO-d 6 , TMS) 6 (ppm) : 2. 14 (3H, s) , 3. 52-3. 62 ( 3 H, m), 5. 8 5 (2H, s) ,7.30-7.36 (1H,m),7.39 (1H, s),7.51(1H, s) ,7.59 (1H,d, 5 J=2Hz),7.61-7.71(1H,m),8.19(lH,d,J=5Hz),9.26(1H,brs), 10.20(1H,brs) ,10.25(lH,brs) Preparation Example 170 Under ice-cooling, 0.08 g of N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- [ (3-chloro-2 10 pyridinyl)methyl]-5-trifluoromethyl-lH-pyrazole-3 carboxamide, 0.05 g of methyl chloroformate, 1 ml of pyridine and 10 ml of acetonitrile were mixed, and the mixture was stirred for 1 hour under ice-cooling. Water was poured into the reaction mixture, and the mixture was extracted with ethyl 15 acetate three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 0.06 g of the present compound (170) of the formula: .424

H

3 C CI

F

3 C N H (170) N N-N H N OCH 3

CH

2 H CI The present compound (170) 1H-NMR(DMSO-d6,TMS)(ppm) :2.20(3H,s) , 3 .53- 3

.

64

(

3 H,m) , 5 .8 6

(

2 H,s),7.41-7.49(3H,m),7.59(1H,s),8.03(1H,d,J=7Hz), 5 8.44(1H,d,J=4Hz),9.32(1H,brs),9.96(1H,brs),10.25(1H,brs) Preparation Example 171 According to the same manner as that of Preparation Example 93, N- [4-chloro-2- (hydrazinocarbonyl) -6 methylphenyl] -1- (3-chloro-2-pyridinyl) -4-iodo-1H-pyrrole- 2 10 carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2-pyridinyl )-1H-pyrrole-2- carboxamide to obtain the present compound (171) of the formula:

H

3 C CI NA N H(1) H N OCH 3 CI N O N H 0 15 The present compound (171) 1H-NMR(DMSO-d6,TMS) (ppm):2.15(3H,s),3.63( 3 H,s), 7

.

2 5(lH,s), 7

.

38 (1H,s),7.40(lH,s),7.49(1H,dd,J=8Hz,5Hz),7.51(lH,s), , 425 8.05(1H,dd,J=8HZ,2Hz),8.43(1H,dd,J=5Hz,2Hz),9.33(lH,brs), 9.72(lH,brs),10.12(1H,brs) Preparation Example 172 According to the same manner as that of Preparation 5 Example 158, the present compound (171) was used in place of the present compound (93) to obtain the present compound (172) of the formula: H3C CI I Oc/ H ___-OCH 3 C1 O N-N N H 0-OCH 3 The present compound (172) 10 1 H-NMR(CDCl3 ,TMS) 6 (ppm) :2.19 (3H, s),3.73 (6H, s) ,7.10 (1H,d, J=lHz),7.14(lH,d,J=1Hz),7.25-7.31(3H,m),7.79(lH,ddJ= 8 Hz, 2Hz),8.31(lH,dd,J=5Hz,2Hz),9.20(lH,s),9.23(lH,brs) Preparation Example 173 According to the same manner as that of Preparation 15 Example 151, 10-chloro-2-[4, 5-dichloro-l-(3-chloro-2 pyridinyl)-1H-pyrrol-2-yl]-4H-naphtho[ 2 ,3-d] [1,3] oxazine-4 one was used in place of 2-[3-bromo-l-(3-chloro-2 pyridinyl)-lH-pyrazol-5-yl] -10-chloro-4H-naphtho[2,3-d] (1,3 ]oxazine-4-one to obtain the present compound (173) of the 20 formula: 426 CI CI ' N H (173) N H -N

OCH

3 C1 O N - ' N H O The present compound (173) H-NMR(CDC1 3 ,TMS)6(ppm):3.60(3H,s),7.

4 6- 7 .59( 2 H,m), 7.69-7.81(2H,m),8.11-8.23(4H,m),8.48-8.52(lH,m), 5 9.32(1H,brs),10.09(lH,brs),10.22(1H,brs) Preparation Example 174 ,According to the same manner as that of Preparation Example 93, 4-bromo-N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl] -1- (2-chloro-3-pyridinyl) -lH-pyrrole-2 10 carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyridinyl )-1H-pyrrole-2- carboxamide to obtain the present compound (174) of the formula: Br

H

3 C C1 N 'P, H N HH (174) \CN H - ,N OCH3 0I N ON H 0 N 15 The present compound (174) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.15( 3 H,s), 3

.

4 5

-

3

.

6 7

(

3 H,m), 7.27(1H,s),7.36(1H,s),7.42(lH,d,J=lHz),7.48-7.54(2H,m), .427 7.94(1H,dd,J=8Hz,lHz),8.42(1H,dd,J=5Hz,1Hz),9.29(1H,brs), 9.73(1H,brs),10.12(1H,brs) Preparation Example 175 According to the same manner as that of Preparation 5 Example 151, 7-bromo-2- [3-bromo-1- (3-chloro-2-pyridinyl) -H-pyrazol-5-yl]-10-chloro-4H-naphtho[2, 3-d[1, 3]oxazine-4 -one was used in place of 2-[(3-bromo-1-(3-chloro-2-pyridinyl) -1H-pyrazol-5-yl)-10-chloro-4H-naphtho[ 2 ,3-d] [1,3]oxazine-4 -one to obtain the present compound (175)of the formula: Br C1 Br , CI 'N H H '(175) ON H .... Ny OCH3 C N H O 10 The present compound (175) 'H-NMR(DMSO-dr>,TMS)5(ppm):3.58-3.70(3H,m),7.46(1H,s), 7 .5 9 (lH,dd,J=8Hz,5Hz),7.93(1H,d,J=9Hz),8.08-8.21(3H,m),8.46 8.53(2H,m),9.36(lH,brs),10.33(lH,brs),10.6 2 (lH,brs) 15 Preparation Example 176 According to the same manner as that of Preparation Example 151, 7, 10-dibromo-2- [3-bromo-1- (3-chloro 2-pyridinyl)-1H-pyrazol-5-yl]-4H-naphtho[ 2 ,3-d] [1, 3]oxazine -4-one was used in place of 2-[3-bromo-1-(3-chloro-2 20 pyridinyl)-1H-pyrazol-5-yl]-10-chloro-4H-naphtho[2, 3-d] [1, 3]oxazine-4-one to obtain the present compound (176) of the .428 formula: Br Br 'N H N H (176) HN OCH3 C N H 0 The present compound (176) 1 H-NMR (DMSO-d 6 , TMS) 5 (ppm) :3. 59-3. 69 (3H,m) ,7 .47 (lH, s) , 5 7.56-7.62(1H,m),7.92(1H,d,J=9Hz),8.10-8.20(3H,m),8.45-8.54 (2H,m),9.35(1H,brs),10.29(1H,brs),10.66(1H,brs) Preparation Example 177 According to the same manner as that of Preparation Example 93, 5-chloro-N-[4-chloro-2-(hydrazinocarbonyl) 10 6-methylphenyll-1-(2-pyridinyl)-1H-pyrrole-2-carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyridinyl )-1H-pyrrole-2-carboxamide to obtain the present compound (177) of the formula:

H

3 C C1 0 /p C N H (177) H q. ,N OCH3 6 ON' H06 15 The present compound (177) 1 H-NMR(DMSO-d 6 ,TMS)5(ppm):2.13(3H,s),3.63(3H,s),6.4 2 (lH,d, ,429 J=4HZ),7.13(1H,d,J=4Hz),7.37(1H,S),7.42-7.47(2H,m),7.50 (1H,d,J=2Hz),7.94(1H,td,J=8Hz,2Hz),8.50(1H,dd,J=5Hz, 2 Hz), 9.33(1H,brs),9.69(1H,brs),10.12(1H,brs) Preparation Example 178 5 According to the same manner as that of Preparation Example 134, 4-bromo-N- [6-bromo-4-chloro-2-

(N

methylhydrazinocarbonyl)phenyl) -1- (3-chloro-2-pyridinyl) -lH-pyrrole-2-carboxamide was used in place of 4-bromo N-[4-chloro-2-(N-methylhydrazinocarbonyl)-6-methylphenyl] 10 1- (3-chloro-2-pyridinyl) -1H-pyrrole-2-carboxamide to obtain the present compound (178) of the formula: Br Br CI N O N N , H (178) H -N OCH3 C"' N O N"'

H

3 C 0 The present compound (178) 1H-NMR(CDCl 3 ,TMS)5(ppm):3.15'(3H,s),3.58(3H,s), 7 .0 4 (1H,d, 15 J=2Hz),7.26(1H,s),7.35(lH,dd,J=8Hz,5Hz),7.46(1H,d,J= 2 Hz), 7 .70(lH,s),7.82(lH,dd,J=8Hz,2Hz),8.43(1H,dd,J=5Hz, 2 Hz), 8.55(lH,brs),8.80(1H,brs) Preparation Example 179 According to the same manner as that of Preparation 20 Example 158, the present compound (173) was used in place of the present compound (93) to obtain the present compound (179) of the formula: 430 CI N H I(OCH3 CI O N-N N H 0r-OCH 3 The present compound (179) H-NMR(CDC1,TMS)5(ppm):3.81(6H,s),7.15(lH,s), 7

.

35 (lH,dd, J=8Hz,5Hz),7.52-7.63(2H,m),7.84(lH,d,J=8Hz), 7 .85(1H,d, 5 J= 8 Hz),8.04(1H,s),8.15(lH,dd,J=8Hz,2Hz),8.41(lH,dd,J=5Hz, 2Hz),8.46(1H,brs),8.68(1H,brs) Preparation Example 180 According to the same manner as that of Preparation Example 122, 6, 8-dibromo-2-[4-bromo-1-(3-cyano-2-pyridinyl) 10 -1H-pyrrol-2- yll-4H-3,1-benzoxazine-4-one was used in place of 6, 8-dibromo-2- [4-bromo-l- (3-chloro-2-pyridinyl) -1H pyrrol-2-yl]- 4 H-3,1- benzoxazine-4-one to obtain the present compound (180) of the formula: Br B Br O Br N N H (180) H N OCH3 NC 0 N N H 0 15 The present compound (180) 1H-NMR(DMSO-d,,TMS)5(ppm):3.62(3H,s),7.36(H,d,J= 2 Hz), 7

.

64 (lH,d,J=2Hz),7.64(1H,s),7.67(H,dd,J=8Hz,5Hz),8.11(lHs), 431 8.47 (1H,dd,J=8Hz, 2Hz) 8.74 (1H,dd,J=5Hz,2Hz) ,9.24 (lH,brs), 10.03(1H,brs),10.14(1H,brs) Preparation Example 181 According to the same manner as that of Preparation 5 Example 122, 6, 8-dibromo-2-[4-bromo-1-(3-trifluoromethyl 2-pyridinyl)-1H-pyrrol-2-yl)- 4

H-

3 , 1- benzoxazine-4-one was used in pla6e of 6,8-dibromo-2-[4-bromo-1-(3-chloro- 2 pyridinyl)-lH-pyrrol-2-yl]- 4

H-

3 ,1- benzoxazine-4-one to obtain the present compound (181) of the formula: Br Br Br o N H (181) F N AH N-N OCH3

F

3 C N 0 N N H 0 10 The present compound (181) 1H-NMR(DMSO-dr>,TMS)(ppm):3.62(3H,s),7.33(1H,s), 7

.

5 0(1H,s), 7

.

63 (lH,s),7.72(1H,dd,J=8Hz,5Hz),8.08(1H,s),8.

3 3 (lH,d, J=8Hz),8.74(1H,d,J=5Hz),9.35(1H,brs),9.88(lH,brs), 15 10.11 (1H, brs) Preparation Example 182 According to the same manner as that of Preparation Example 93, N-[4-chloro-2-(hydrazinocarbonyl)-6 methylphenyl) -- (3-chloro-2-pyridinyl) -5-iodo-lH-pyrrole-2 20 carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2-pyridinyl 432 )-1H-pyrrole-2-carboxamide to obtain the present compound (182) of the formula:

H

3 C CI SN H (182) N H -.. N OCH3 C 0 N )r N H 6 The present compound (182) 5 1H-NMR(DMSO-d 6 ,TMS)5(ppm):2.11(3H,s),3.63( 3 H,s), 6

.

63 (lH,d, J=4Hz),7.19(1H,d,J=4Hz),7.40(1H,s),7.43(1H,s), 7

.

52 (lH,dd, J=8Hz,5Hz),8.06(1H,dd,J=8Hz,2Hz),8.48(1H,dd,J=5Hz, 2 Hz), 9.28(1H,brs),9.71(1H,brs),10.13(lH,brs) Preparation Example 183 10 According to the same manner as that of Preparation Example 72, 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol 5-yl]-8-methyl-6-nitro- 4 H-3,1-benzoxazine-4-one was used in place of 2-[3-bromo-l- (3-chl'oro-2-pyridinyl) -1H-pyrazol-5 yl)-8-chloro-4H-3,1-benzoxazine-4-one to obtain the present 15 compound (183) of the formula: Br H 3 C NO 2 'N H H (183) H -NA OCH3 0 N H 0 The present compound (183) 'H-NMR(DMSO-d6,TMS)6(ppm):2.29(3H,s),3.51- 3

.

68

(

3 H,m), 7

.

37

-

,433 7.42(1H,m),7.58-7.65(1H,m),8.14-8.22(2H,m),8.32-8.39(lH,m), 8.48-8.54(lH,m),9.39(1H,brs),10.41(1H,brs),10.58(1H,brs) Preparation Example 184 To a mixture of 0.26 g of N,N'-dimethylhydrazine 5 dihydrochloride, 2 ml of water, 0.5 g of potassium carbonate and 10 ml of N,N-dimethylformamide was added 0.20 g of 2- [3-bromo-1-(3-chloro-2-pyridinyl) - 1H-pyrazol-5-yl)-8 methyl-6-nitro-4H-3,1-benzoxazine-4-one. The resulting mixture was stirred at room temperature for 2 hours. The 10 reaction mixture was poured into water, and extracted with ethyl, acetate three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 15 3-bromo-1-(3-chloro-2-pyridinyl)-N-[ 2

-(N,N'

dimethylhydrazinocarbonyl)-6-methyl-4-nitrophenyl]-1H pyrazole-5-carboxamide of the formula: Br

H

3 C

NO

2 0 -~ N, N CH 3 N H NH C1 0 N

H

3 C Under ice-cooling, 0.1 g of methyl chloroformate was added 20 to a mixture of 3-bromo-1-(3-chloro-2-pyridinyl)-N [2-(N,N'-dimethylhydrazinocarbonyl)-6-methyl-4 nitrophenyl)-1H-pyrazole-5-carboxamide, 1 ml of pyridine and .434 10 ml of acetonitrile, and the mixture was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate two times. The organic layers were combined, washed successively 5 with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0. 07 g of the present compound (184) of the formula: Br, H 3 C NO 2 N N CH 3 H N OCH 3 (184) CI NN |

H

3 C 0 10 The present compound (184) 1H-NMR(DMSO-d 6 ,TMS)56(ppm):2.27-2.37(3H,m),2.70- 2 .88( 3 Hm), 2.88- 3 .11( 3 H,m),3.45-3.74(3H,m),7.38-7.46(1H,m), 7 .6 3 (lH,dd, J=8Hz,5Hz),7.92-8.04(1H,m),8.21(lH,dd,J=8Hz,1Hz),8.24-8.34 15 (1H,m),8.51(1H,dd,J=5Hz,lHz),10.40-10.75(lH,m) Preparation Example 185 According to the same manner as that of Preparation Example 122, 6,8-dibromo-2-[4-bromo-l (3-nitro-2 pyridinyl) -1H-pyrrol-2-yl] -4H-3, 1-benzoxazine-4-one was used 20 in place of 6, 8-dibromo-2- [4-bromo-1- (3-chloro-2-pyridinyl) 1H-pyrrol-2-yl]-4H-3,1-benzoxazine-4-one to obtain the present compound (185) of the formula: ,435 Br Br Br N N H (185) H .-N OCH 3 0 2 N N N O N 02N 0 The present compound (185) H-NMR(DMSO-d6,TMS)5(ppm):3.61(3H,s),7.36(1H,s),7.57(1H,d,

J=

2 Hz),7.62(1H,s),7.78(H,dd,J=8Hz,5Hz),8.lO(lH,d,J= 2 Hz), 5 8.61(lH,dd,J=8Hz,2Hz),8.79(1H,dd,J=5Hz,2Hz),9.

24 (lH,brs), 9.95(1H,brs),10.12(lH,brs) Preparation Example 186 According to the same manner as that of Preparation Example 122, 6,8-dibromo-2-[4-bromo-1-(3-bromo-2 10 pyridinyl)-1H-pyrrol-2-yl]-4H-3,1-benzoxazine-4-one was used in place of 6,8-dibromo-2- [4-bromo-l- (3-chloro-2-pyridinyl) 1H-pyrrol-2-yl) -4H-3, 1-benzoxazine-4-one to obtain the present compound (186) of the formula: Br B Br\ B Br NH H(18 N H A -N OCH 3 Br N N 0 H 0 15 The present compound (186) 1H-NMR(DMSO-dG,TMS)5(ppm):3.61(3H,s),7.32(1H,s), 7

.

4 0(lH,dd, J=8Hz,5Hz),7.42 (1H,s) ,7. 63(1H,s) ,8.10 (1H,s) ,8.17 (lH,d, 436 J=8Hz),8.46(lH,d,J=5Hz),9.36(lH,brs),9.90(lH,brs),10.1 6 (lH, brs) Preparation Example 187 According to the same manner as that of Preparation 5 Example 93, 4-bromo-N-[4-chloro-2-(hydrazinocarbonyl)-6 methylphenyl) -1- (3-chloro-4-pyridinyl) -lH-pyrrole-2 carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyridinyl )-1H-pyrrole-2-carboxamide to obtain the present compound 10 (187) of the formula:

H

3 C C1 Br / N N H (187) H ... N OCH3 CI 0 N H O N The present compound (187) 1H-NMR(DMSO-ddTMS) (ppm) :2.16(3H,s) ,3.41-3. 68 ( 3 H,m), 7.

29 (1H,brs),7.33-7.40(1H,m),7.43(lH,d,J=2Hz),7.52(1H,d,J=2Hz), 15 7

.

5 5(1H,d,J=5Hz),8.59(1H,d,J=5Hz),8.72(lH,brs),9.30(lH,brs), 9.78(lH,brs),10.15(1H,brs) Preparation Example 188 According to the same manner as that of Preparation Example 72, 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol 20 5-yl]-6-chloro-4H-3,1-benzoxazine-4-one was used in place of 2- [3-bromo-l- (3-chloro-2-pyridinyl) -lH-pyrazol-5-yl] -8- ,437 chloro-4H-3,1-benzoxazine-4-one to obtain the present compound (188) of the formula: Br. C1 'N H H OCH 3 (188) CI O N ( N H O The present compound (188) 5 H-NMR(DMSO-dE,TMS) 6(ppm) :3.68 (3H,brs) ,7.23(1H,brs)

,

7

.

62 (lH,dd,J=9Hz,2Hz), 7.67 (1H,dd,J=8Hz, 5Hz) ,7.88 (1H,s) ,8.18 (lH,d,J=9Hz),8.25(lH,dd,J=8Hz,1Hz),8.54(1H,dd,J=5Hz,lHz), 9.49(1H,brs),10.78 (1H,brs),11.77(1H,brs) Preparation Example 189 10 According to the same manner as that of Preparation Example 115, 3-bromo-N-[4-chloro-2-(N methylhydrazinocarbonyl)phenyl]-1-(3-chloro-2-pyridinyl) 1H-pyrazole-5-carboxamide was used in place of 3-bromo N- [4-chloro-2- (N-methylhydrazinocarbonyl) -6-methylphenyl) 15 1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide to obtain the present compound (189) of the formula: Br / CI N N H (189) N H -N OCH3

H

3 C 0 The present compound (189) 1H-NMR(DMSO-d 6 ,TMS)6(ppm):3.07(3H,s),3.51(3H,brs), 7

.

29 ,438 (2H,brs),7.47-7.54(2H,m),7.65(1H,dd,J=8Hz,5Hz),8.2 2 (lH,dd, J=8Hz,1Hz),8.52(1H,dd,J=5Hz,1Hz),9.55(1H,brs),10.14(1H,brs) Preparation Example 190 According to the same manner as that of Preparation 5 Example 119, 3-bromo-N-[4-chloro-2-(N,N' dimethylhydrazinocarbonyl)phenyl]-1-(3-chloro-2-pyridinyl) 1H-pyrazole-5-carboxamide was used in place of 3-bromo-N [4-chloro-2-(N,N'-dimethylhydrazinocarbonyl)-6-methylphenyl ]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5- carboxamide to 10 obtain the present compound (190) of the formula: Br, O CI 'N 'N CH 3 H N OCH 3 (190) Clt O N "N OH

H

3 C 0 The present compound (190) 1H-.NMR(DMSO-d 6 ,TMS)5(ppm)):2.83-3.07(6H,m),3.52- 3

.

7 0( 3 H,m), 7

.

29 -7.60(4H,m),7.64(1H,dd,J=8Hz,5Hz),8.22(lH,dd,J=8Hz, 2 Hz), 15 8.51(1H,dd,J=5Hz,2Hz),10.53-10.68(1H,brm). Preparation Example 191 According to the same manner as that of Preparation Example 93, 4,5-dichloro-N-[4-chloro-2-(hydrazinocarbonyl) 6-methylphenyl]-1-(2-pyridinyl)-1H- pyrrole-2-carboxamide 20 was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyridinyl )-1H-pyrrole-2-carboxamide to obtain the present compound ,439 (191) of the formula:

H

3 C CI C1 N H N H -N

OCH

3 N H 0 The present compound (191) 1 H-NMR(DMSO-d 6 ,TMS)5(ppm):2.13(3H,s),3.63(3H,s),7.24(1H,s), 5 7.35(1H,s),7.49-7.51(3H,m),7.97(1H,td,J=8Hz,2Hz),8.52(1H,dd, J=6Hz,2Hz),9.31(1H,brs),9.78(1H,brs),10.12(lH,brs) Preparation Example 192 According to the same manner as that of Preparation Example 93, 3,5-dichloro7N-[4-chloro-2-(hydrazinocarbonyl) 10 -6-methylphenyl] -1- (2-pyridinyl) -lH- pyrrole-2-carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2-pyridinyl )-1H-pyrrole-2-carboxamide t6 obtain the present compound (192) of the formula: C1 H 3 C C1 N H (192) CI N H O -N

OCH

3 N H 0 15 The present compound (192) 1H-NMR(DMSO-dTMS)(ppm):2.09(3H,s),3.

68

(

3 H,s), 6

.

69 (lH,s), 1 440 7.42(1H,s),7.48-7.60(3H,m),7.94-8.01(1H,m),8.51(1H,d, J=5Hz),9.37(1H,brs),9.71(lH,brs),10.33(lH,brs) Preparation Example 193 According to the same manner as that of Preparation 5 Example 93, 4-bromo-N-1[4, 6-dibromo-2- (hydrazinocarbonyl) phenyl]-5-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2 carboxamide was used in place of 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro-2-pyridinyl )-1H-pyrrole-2-carboxamide to obtain the present compound 10 (193) of the formula: , Br B Br Br CI N N H (193) H -N OCH 3 ( N 0 H The present compound (193) 1 H-NMR(DMSO-d 6 ,TMS)6(ppm):3.62(3H,s),7.47(1H,s),7.58(1H,dd,

J=

8 Hz,5Hz),7.63(lH,s),8.10(1H,s),8.15(1H,d,J=8Hz),8.51(lH,d, 15 J=5Hz),9.34(1H,brs),10.00(1H,brs),10.15(lH,brs) Preparation Example 194 According to the same manner as that of Preparation Example 128, 4-bromo-N-[4, 6-dibromo-2- (hydrazinocarbonyl) phenyl] -5-chloro-1- (3-chloro-2-pyridinyl) -lH-pyrrole-2 20 carboxamide was used in place of 4,5-dibromo-N-[4-chloro 2- (hydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2- 441 pyridinyl)-1H-pyrrole-2- carboxamide to obtain the present compound (194) of the formula: Br 0Br Br Cl N N H (194) H .,..N N(CH 3

)

2 N H O The present compound (194) 5 lH-NMR(DMSO-d,TMS)6(ppm):2.85(6H,s),7.53(lH,s), 7 .5 9 (lH,dd, J=8Hz,5Hz),7.70(lH,s),8.06(lH,s),8.16(lH,d,J=8Hz),8.51(lH,d, J=5Hz,),8.56(lH,brs),9.82(lH,brs),9.97(lH,brs) Preparation Example 195 A mixture of 0.59 gof 3-bromo-N-[4,6-dibromo-2 10 (hydrazinocarbonyl)phenyl]-1-(3-chloro-2-pyridinyl)-lH pyrazole-5-carboxamide, 0.23 g of propargyl chloroformate, 0.16 g of pyridine and 2 ml of acetonitrile was stirred at room temperature for 1 hour. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The 15 organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was washed with ethyl acetate to obtain 0.22 g of the present compound (195) of the formula: ,442 Br B Br B Br N' NH (195) 'N H -N OCH 2 C CH CI 0 N N H o 71 The present compound (195) 1H-NMR(DMSO-d 6 ,TMS) 5(ppm) :3. 56 (1H, s) ,4.71 (2H, s) ,7. 41(1H,s) 7.60(1H,dd,J=8Hz,5Hz),7.66(1H,s),8.14-8.16(2H,m),8.50(lH,dd, 5 J=5Hz,lHz),9.60(lH,brs),10.29(1H,brs),10.50(1H,brs). Preparation Example 196 ,According to the same manner as that of Preparation Example 34, propargyl chloroformate was used in place of methyl chloroformate to obtain the present compound (196) of the 10 formula:

.

H

3 C CI Br O N, N H (196) N H -N OCH 2 C=CH CI O 0 N N H O The present compound (196) 1H-NMR (DMSO-de, TMS) ) (ppm) :2.15 (3H, s) , 3. 5 6 (1H, brs) , 4. 7 2

(

2 H, s), 7 .35(lH,s),7.39(1H,brs),7.55(1H,s),7.61(1H,dd,J=8Hz,5Hz), 15 8.17(1H,dd,J=BHz,1Hz),8.50(lH,dd,J=5Hz,1Hz),9.55(lH,s), 10.23-10.26(2H,brm). Preparation Example 197 443 According to the same manner as that of Preparation Example 10, 3-bromo-N- (4-chloro-2- (hydrazinocarbonyl) 6-methylphenyl] -1- (3-chloro-2-pyridinyl) -1H-pyrazole-5 carboxamide was used in place of N-[4-chloro-2 5 (hydrazinocarbonyl)-6-methylphenyl)-1-(3-chloro-2-pyridinyl )-3-trifluoromethyl-1H-pyrazole-5-carboxamide to obtain the present compound (197) of the formula: 'Br OHA N'N N H (197) N H -N

N(CH

3

)

2 Ci 0 N 'N H o The present compound (197) 10 H-NMR(DMSO-drTMS)6(ppm):2.20(3H,s),2.93(6H,s), 7 .50- 7

.

5 2 (2H,m),7.58(1H,brs),7.67(lH,dd,J=8Hz,5Hz),8.24(lH,d,J=8Hz), 8.56(lH,d,J=5Hz),8.60(1H,s),9.89(1H,brs),10.23(lH,brs) Preparation Example 198 To a mixture of 0.20 g of the present compound (197), 0.10 15 ml of triethylamine and 5 ml of tetrahydrofuran was added dropwise 0.040 ml of methyl chloroformate under ice-cooling. The mixture was stirred at room temperature for 2.5 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers 20 were combined, washed with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium ,444 sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to 0.13 g of the present compound (198) of the formula: Br

H

3 C CI Br 00 N N (~'198)0 N H _-N(CH 3

)

2 C1 O N-N C0 H -OCH 3 5 The present compound (198) H-NMR(CDCl 3 ,TMS) 5 (ppm) :2.22 (3H, s) , 3. 05 (3H,brs) , 3.15 (3H, brs),,3.76(3H,s),6.99(lH,s),7.35-7.38(2H,m), 7

.

44 (lH,s), 7.86(1H,d,J=8Hz),8.39(1H,s),8.46(1H,d,J=5Hz),9.40(lH,s) 10 Preparation Example 199 A mixture of 1.0 g of 2-[3-bromo-l-(3-chloro-2 pyridinyl) -lH-pyrazol-5-yl] -6-chloro-8-methyl-4H-3, 1 benzoxazine-4-one, 1.33 g of formic hydrazide and 40 ml of N,N-dimethylformamide was stirred at 50*C for 3.5 hours, and 15 at 70*C for 7 hours. The reaction mixture was allowed to cool to room temperature, and thereto water was poured. The mixture was extracted with methyl tert-butyl ether. The organic layer was washed with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and 20 concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.36 g of the present compound (199) of the formula: '445

H

3 C C1 0 Br O N N H (199) H N H 0 N' N H 0 The present compound (199) H -NMR(DMSO-d6,TMS)6(ppm) :2.10-2.21 (3.0H,m),7.25-7.62 (4.7H, m),7.79-7.81(0.2H,m),8.05(0.3H,s),8.16(1.0H,d,J=8Hz), 5 8.49(1.OH,d,J=5Hz),9.48-9.55(0.7H,m),10.05-10.45(2.1H,m) Preparation Example 200 ,To a mixture of 0.20 g of the present compound (115), 0.14 ml of triethylamine and 10 ml. of acetonitrile was added 0.12 ml of methyl chloroformate at room temperature. The resulting 10 mixture was stirred at room temperature for 18 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous 15 magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.010 g of the present compound (200) of the formula: 446

H

3 C Ci Br O N'N OCH3 (200) N H __ -OCH 3 C1 O N-N N H 3 C I -OCH 3 The present compound ('200) 1H-NMR(CDClaTMS)6(ppm) :2.21(3H,s) ,3.23( 3 H,s) , 3 .8 9

(

6 H,brs) , 6.

46 (lH,s),7.08(1H,s),7.30(1H,s),7.43(lH,dd,J=8Hz,5Hz), 5 8.92(1H,d,J=8Hz),8.51(1H,d,J=5Hz),9.21(lH,s) Preparation Example 201 According to the same manner as that of Preparation Example 158, that the present compound (122) was used in place of the present compound (93) to obtain the present compound 10 (201) of the formula: Br Br Br N H21OCH 3 ) CI 0 N-N N H 0-OCH 3 The present compound (201) 'H-NMR(CDCl 3 ,TMS)6(ppm) :3.74 (6H,s) ,7.08 (2H,s) , 7 .30(H,dd, J=8Hz,5Hz),7.66(1H,s),7.82(1H,d,J=8Hz), 7

.

86 (lH,s), 15 8.28(1H,brs),8.32(1H,d,J=5Hz),8.60(lH,brs) Preparation Example 202 According to the same manner as that of Preparation Example 134, 4-bromo-N-[4,6-dibromo-2-(N methylhydrazinocarbonyl)phenyl] -1- (3-chloro-3-pyridinyl)

-

-447 1H-pyrrole-2-cabroxamide was used in place of 4-bromo N-[4-chloro-2-(N-methylhydrazinocarbonyl)-6-methylphenyll 1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxamide to obtain the present compound (202) of the formula: B Br Br . N H N HH (202) C1H 0 - N OCH3

H

3 C 0 5 The present compound (202) H-NMR(CDCl 3 ,TMS)5(ppm):3.05(0.5H,brs),3.13(2.5H,s),3.

5 9 (2.51{,s),3.82(0.5H,brs),7.05(1.0H,d,J=2Hz),7.21(1.0H,s), 7.35(1.3H,dd,J=8Hz,5Hz),7.42(1.OH,s),7.65(2.OH,s),7.82(1.OH, 10 d,J=8Hz),8.43(1.OH,dd,J=5H,2Hz),8.57(0.7H,s) Preparation Example 203 According to the same manner as that of Preparation Example 115, 3-bromo-N-[4,6-dibromo-2-(N methylhydrazinocarbonyl)phenyl)-1-(3-chloro-2-pyridinyl) 15 1H-pyrazole-5-carboxamide was used in place of 3-bromo N-[4-chloro-2-(N-methylhydrazinocarbonyl)-6-methylphenyl] 1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide to obtain the present compound (203) of the formula: BBr Br 'N N H (203) NIH N OCH3 C1 N 0 N' 'I H3C 0 448 The present compound (203) 'H-NMR(100*C,DMSO-d 6 ,TMS)6(ppm) :2.96(3H,S),3.04(3H,brs), 7.30 (lH, s) ,7.38 (1H, s) ,7.58 (lH,dd, J=8Hz, 5Hz), 7.96(lH,s) ,8.11 (lH,d,J=8Hz),8.47(lH,d,J=5Hz),8.68(lH,brs),10.08(lH,brs) 5 Preparation Example 20-4 A mixture of 0.30 g of 3-bromo-N-[4,6-dibromo- 2 (N,N' -dimethylhydrazinocarbonyl)phenyl] -1- (3-chloro-2 pyridinyl)-lH-pyrazole-5-carboxamide, 0.15 ml of methyl chloroformate and 3 ml of pyridine was stirred at room 10 temperature for 2.5 hours. Then, 0.08 ml of methyl chloroformate was added thereto, and the mixture was stirred for 1 hour. Then, 0.08 ml of methyl chloroformate was added thereto, and the mixture was further stirred for 0.5 hour. Water was poured into the reaction mixture, and the mixture was 15 extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.24 g of the present compound (204) of the formula: Br 0Br Br N N

CH

3 (204) H N OCH 3 Ci O N N

H

3 C 0 20 The present compound (204) 1H-NMR (DMSO-d 6 , TMS) 6 (ppm) :2. 71 (1. 4H, s) , 2 .83 (1. 6H, s) , 449 2.94(1.5H,s),3.06(l.5H,s),3.35-3.70(3.OH,m),7.41(0.5H,S), 7.45(0.6H,s),7.47(0.6H,s),7.60-7.64(1.3H,m),8.07(0.5H,d, J=2Hz),8.13(0.5H,s),8.18(1.OH,d,J=8HZ),8.50(1.OH,m), 10.52(0.5H,s), 10.67(0.5H,s) 5 Preparation Example 205 According to the same manner as that of Preparation Example 147, 4-bromo-N-[4,6-dibromo-2-(N,N' dimethylhydrazinocarbonyl)phenyl] -1- (3-chloro-2-pyridinyl) 1H-pyrrole-2-carboxamide was used in place of 10 4-bromo-N-[4-chloro-2-(N,N'-dimethylhydrazinocarbonyl)-6 methylphenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2 carboxamide to obtain the present compound (205) of the formula: Br Br Br Br N Cs (205) N N OCH3 CI 0 N ''i'

H

3 C 0 15 The present compound (205) 1 H-NMR(DMSO-d 6 ,TMS)6(ppm):2.73(1.4H,s), 2

.

8 2 (1.8H,s), 2.89(1.3H,s),3.06(1.5H,s),3.35-3.70(3.OH,m),7.32(0.5H,s), 7.34-7.38(0.6H,m),7.43(0.5H,s),7.48-7.53(2.4H,m),8.0 3 (0.

4 H, d,J=2Hz),8.07-8.10(1.6H,m),8.43-8.45(1.0H,m),9.

93 (0.5H,s), 20 10.07(0.5H,s) Preparation Example 206 According to the same manner as that of Preparation *450 Example 136, 4-bromo-N-(4,6-dibromo-2-(N methylhydrazinocarbonyl) phenyl] -1- (3-chloro-2-pyridinyl) 1H-pyrrole-2-carboxamide was used in place of 4-bromo-N [4-chloro-2-(N-methylhydrazinocarbonyl)-6-methylphenyl]-1 5 (3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxamide to obtain the present compound (206) of the formula: Br, Br Br N N H (206) HY . -N N(CH3)2 CI0 N~ CI"1N H3C O The present compound (206) 'H-NMR (CDC13,TMS) 6(ppm) :2.47 (6H, s) ,3.29 (3H, s) ,7.04 (lH,d, 10 J=2Hz),7.31(1H,dd,J=8Hz,5Hz),7.43(1H,d,J=2Hz),7.51(1H,d, J=2Hz),7.53 (lH,d, J=2Hz),7.80 (1H,dd, J=8Hz,2Hz),8.09 (lH,s), 8.41(lH,dd,J=5Hz,2Hz),9.67(lH,s) Preparation Example 207 According to the same manner as that of Preparation 15 Example 199, 6,8-dibromo-2-[4-bromo-1-(3-chloro-2-pyridinyl) -lH-pyrrol-2-yl]-4H-3,1-benzoxazine- 4-one was used in place of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-H-pyrazol-5-yl]-6 chloro-8-methyl-4H-3,1- benzoxazine-4-one to obtain the present compound (207) of the formula: 451 Br 0Br Br N H N N H (207) C N O N H C1 NZ 0 N N H O The present compound (207) 1 H-NMR(DMSO-d 6 ,TMS)6(ppm):7.31(0.6H,S),7.

3 8 (0.

3 H,s), 7.44(0.6H,d,J=2Hz),7.47-7.52(1.5H,m),7.65-7.75(1.3H,m), 5 8.03-8.12(2.7H,m),8.43(1.OH,dd,J=5Hz,2Hz),9.49-9.52(0.3H,m), 9.94-9.99(0.4H,m),10.17(1.OH,s),10.39-10.44(1.OH,m) Preparation Example 208 According to the same manner as that of Preparation Example 199, 2-[3-bromo-1- (3-,chloro-2-pyridinyl) -1H-pyrazol 10 5-yl) -6, 8-dibromo-4H-3, 1-benzoxazine-4-one was used in place of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5 yl)-6-chloro-8-methyl-4H-3,1-benzoxazine-4-one to obtain the present compound (208) of the formula: B Br Br NN H (208) Cl HI O NN H 0 N "N H O 15 The present compound (208) 1 H-NMR(DMSO-d, TMS)(ppm):7.41(0.7H,s),7.

4 5 (0.

3 H,s ), 7.58-7.63(1.0H,m),7.69-7.73(1.0H,m),7.77-7.79(0.4H,m), 8.04(0.6H,s),8.13-8.18(2.OH,m),8.49-8.51(1.OH,m), 9.55-9.58(0.4H,m),10.18(0.6H,s),10.45-10.60(2.OH,m) .452 Preparation Example 209 A mixture of 0.30 g of 6,8-dibromo-2-[4-bromo-1-(3-chloro -2-pyridinyl) -lH-pyrrol- 2-yl)-4H-3,1-benzoxazine-4-one, 0.28 g of N-methyl-N- methoxycarbonylhydrazine and 15 ml of 5 N,N-dimethylformamide was stirred at 80*C for 35 hours, and then allowed to cool to room temperature. Water was poured into the reaction mixture, and the mixture was extracted with methyl tert-butyl ether. The organic layer was washed successively with water and an aqueous saturated sodium chloride solution, 10 dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0. 18 g of the present compound (209) of the formula: Br Br Br / N CH (209) H ..N OCH 3 CI N

N

N H 0 15 The present compound (209) H-NMR (DMSO-d, TMS) 5 (ppm) :2.8 4 (3H, s) , 3. 45- 3 .70 ( 3 H, brm) , 7.38(lH,brs),7.47(lH,d,J=2Hz),7.50(1H,dd,J=8Hz,5Hz), 7.54(1H,d,J=2Hz),8.05(1H,dd,J=8Hz,2Hz),8.12(lH,d,J= 2 Hz), 8.41(lH,dd,J=5Hz,2Hz),9.95(lH,s),10.50(1H,s) 20 Preparation Example 210 A mixture of 0.16 g of 4-bromo-N-[4,6-dibromo-2-(N,N' dimethylhydrazinocarbonyl)phenyl]-1-(3-chloro-2-pyridinyl)- 453 1H-pyrrole-2-carboxamide, 0.12 ml of N,N-dimethylcarbamoyl chloride and 0.2 ml of pyridine was stirred at 80*C for 5 hours and then allowed to cool to room temperature. Water was poured into the reaction mixture, and the mixture was extracted with 5 ethyl acetate. The organic layer was washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0. 15 g of the present 10 compound (210) of the formula: Br. Br Br N CH 3 (210) H N N(CH 3

)

2 C0 N

H

3 C 0 The present compound (210) 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.44 (4.5H, s), 2 .58 ( 3 .OH, s), 2 .74(1.5H,brs),2.78(1.OH,s),'3.12(2.OH,s),7.14(0.

7 H,d,J= 2 Hz), 15 7.32(0.7H,d,J=2Hz),7.38(0.3H,s),7.47-7.54(2.3H,m), 8.00(0.7H,d,J=2Hz),8.07-8.10(l.3H,m),8.42-8.45(1.OH,m), 9.95(0.7H,brs),10.08 (0.3H,brs) Preparation Example 211 A mixture of 0.16 g of 3-bromo-N-[4,6-dibromo-2-(N,N' 20 dimethylhydrazinocarbonyl)phenyl) -1- (3-chloro-2-pyridinyl) 1H-pyrazole-5-carboxamide, 0.12 ml of N,N-dimethylcarbamoyl chloride and 2 ml of pyridine was stirred at 80 0 C for 5 hours, 454 and then allowed to cool to room temperature. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and an aqueous saturated sodium chloride solution, dried 5 over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0. 12 g of the present compound (211) of the formula: ' Br Br Br 0

SCH

3 (211) H .N N(CH 3

)

2 ci 0 N'

H

3 C 0 10 The present compound (211) IH-NMR(DMSO-d 6 ,TMS)5(ppm):2.35(4.5H,s), 2

.

4 9 (2.OH,s), 2 .57(1.0H,brs),2.67(l.5H,brs),2.73(1.0H,s), 3 .05( 2 .OH,s), 7 .10(0.

7 H,s),7.34(0.7H,s),7.39(0.3H,s),7.52-7.5 7 (1.

3 Hm), 7.97(0.7H,d,J=2Hz),8.06(0.3H,s),8.11(1.OH,dd,J=8Hz,2Hz), 15 8.41-8.45(1.OH,m),10.49(0.7H,s),10.62(0.3H,s) Preparation Example 212 According to the same manner as that of Preparation Example 160, 3-bromo-N-[4,6-dibromo-2-(N methylhydrazinocarbonyl)phenyll-1-(3-chloro-2-pyridinyl) 20 1H-pyrazole-5-carboxamide was used in place of 3-bromo-N [4-chloro-2-(N-methylhydrazinocarbonyl)-6-methylphenyl]-1 (3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxamide to obtain 455 the present compound (212) of the formula: Br 0Br Br N'N .N H (212) H -N

N(CH

3

)

2 CI N O N

H

3 C O The present compound (212) IH-NMR (CDCl, TMS) 5 (ppm) :2.50 (6H, s) , 3.28 (3H, S) , 7 .

3 l8 (1H, dd, 5 J=8Hz,5Hz),7.46(1H,d,J=2Hz),7.50(lH,s), 7 .55(lH,d,J= 2 Hz), 7. 78 (1H, s) ,7. 86 (1H, d, J=8Hz) , 8. 46 (1H, d, J=5Hz) ,10.20 (lH, s) . Preparation Example 213 ,According to the same manner as that of Preparation Example 114, 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol 10 5-yl]-6,8-dibromo-4H-3,1-benzoxazine- 4 -one was used in place of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5 yl]-6-chloro-8-methyl-4H-3,1-benzoxazine- 4 -one to obtain the present compound (213) of the formula: Br Br Br O N' N

CH

3 (213) H -' 'N

OCH

3 N H 15 The present compound (213) H-NMR(DMSO-d,)6(ppm):2.87(3H,s),3.4 6

-

3

.

66

(

3 H,brm), 7.46(1H, s),7.58- 7

.

6 1(2H,m),8.13-8.18 (2H,m),8.47 (1H,dd, J=5Hz, 2Hz),10.54(1H,s),10.61(1H,s) Preparation Example 214 456 According to the same manner as that of Preparation Example 34, 2-methoxyethyl chloroformate was used in place of methyl chloroformate to obtain the present compound (214) of the formula: Br.

H

3 C CI r O / N N H (214) H .- N OCH 2

CH

2 0CH 3 C N 0 N y N H O 5 The present compound (214) 'H-NMR(CDCl 3 ,TMS)6(ppm) :2.21(3H,s) 3.39 (3H,brs), 3.61(2H,brs),4.31(2H,brs),6.96(lH,brs),7.01(1H,s), 7 .32-7.39(3H,m),7.85(1H,dd,J=8Hz,2Hz),8.03(lH,brs), 10 8.41(1H,d,J=5Hz),9.47(lH,s) Preparation Example 215 According to the same manner as that of Preparation Example 95, the present compound (214) was used in place of the present compound (34) to obtain the present compound (215) of 15 the formula:

H

3 C CI Br O / 0 N N" H q _ >-OCH 2

CH

2 0CH 3 (215) C1 O N-N N H , -OCH 3 The present compound (215) ,457 'H-NMR(CDC1 3 ,TMS)6(ppm):2.24(3H,s),3.31( 3 H,s), 3.58(2H,t,J=5Hz),3.83(3H,s),4.32(2H,brs),6.98(1H,s), 7.32-7.37(2H,m),7.46(1H,d,J=2Hz),7.88(1H,d,J=8Hz), 8.34 (lH,d,J=5Hz),8.70(1H,s),9.33(1H,s) 5 Preparation Example 216 According to the same manner as that of Preparation Example 34, 2,2,2-trichloroethyl chloroformate was used in place of methyl chloroformate to obtain the present compound (216) of the formula: Br\

H

3 C 5 CI H -N OCH 2 CCf3 CI ON N N H O 10 The present compound (216) 'H-NMR(DMSO-d 6 ,TMS)(ppm):2.22(3.OH,s), 4

.

8 9 (0.

4 H,s), 4

.

97 (1.6H,s),7.41(1.OH,s),7.46(0.8H,s),7.53(0.2H,s), 7.62(1.OH,s),7.67(1.0H,dd,J=8Hz,5Hz),8.24(1.OH,dd,J=8Hz, 15 2Hz),8.56(1.OH,dd,J=5Hz,2Hz),9.52(0.2H,s),10.00(0.8H,s), 10.31-10.36(1.0H,brm),10.41(0.8H,s),10.50(0.2H,s) Preparation Example 217 According to the same manner as that of Preparation Example 195, 2,2,2-trichloroethyl chloroformate was used in 20 place of propargyl chloroformate to obtain the present compound (217) of the formula: 458 Br Br Br O Br N N H 'N H N OCH 2 CCl 3 (217) "N H . The present compound (217) 1H-NMR(DMSO-d6,TMS)6(ppm):4.83-4.90(2.H,brm), 7

.

4 0(1.OH,s), 7. 60 (1.OH, dd, J=8Hz, 5Hz) ,7. 67 (0.7H, s) ,7.74 (0.3H, s) ,8. 14-8.18 5 (2.OH,m) ,8.50(1.OH,d,J=5Hz) ,9.51(0.3H,s) ,9.99(0.7H,s), 10.41(0.7H,s),10.48-10.54(1.3H,m) Preparation Example 218 According to the same manner as that of Preparation Example 34, butyl chloroformate was used in place of methyl 10 chloroformate to obtain the present compound (218) of the formula: Br 0 H 3 C Ci N' N N H (218) H N OCH 2

CH

2

CH

2

CH

3 C0 0 N N H O The present compound (218) 'H-NMR(DMSO-d6,TMS)6(ppm):0.90(3H,brs),1.36(2H,brs),1.56(2H, 15 brs),2.15(3H,s),3.92-4.06(2H,brm),7.34-7.39(2H,brm), 7 .55(lH, d,J=2Hz),7.61(1H,dd,J=8Hz,5Hz),8.17(lH,dd,J=8Hz, 2 Hz), 8.49(1H,dd,J=5Hz,2Hz),9.26(lH,s),10.13(1H,s),10.23(1H,s) 459 Preparation Example 219 According to the same manner as that of Preparation Example 95, the present compound (218) was used in place of the present compound (34) to obtain the present compound (219) o/ 5 the formula:

H

3 C Br O -' CI N/ NO N H _ -OCH 2

CH

2

CH

2

CH

3 (219) CI O' N-N N H ,>-OCH 3 The present compound (219) 'H-NMR(CDCl 3 ,TMS)5(ppm):0.93(3H,t,J=7Hz),1.38(2H,qt,J=7Hz, 7Hz),1.65(2H,tt,J=7Hz,7Hz),2.23(3H,s),3.81(3H,s),4.24(2H,t, 10 J=7Hz),6.97(lH,s),7.34-7.38(2H,m),7.44(1H,d,J=2Hz),7.88(lH, dd,J=8Hz,2Hz),8.35(lH,s),8.38(lH,dd,J=5Hz,2Hz),9.24(1H,s) Preparation Example 220 A mixture of 0.30 g of 3-bromo-N-(4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyridinyl 15 )-1H-pyrazole-5-carboxamide, 0.10 g of methoxyacetyl chloride and 3 ml of pyridine was stirred at room temperature for 2.5 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, and was washed with an aqueous 20 saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.

. 460 The resulting residue was sub-ected to silica gel column chromatography to obtain 0.21 g of the present compound (220) of the formula: Br, H3C I" C1 Br O C N H N CH 2

OCH

3 (220) CI N N < 5 The present compound (220) 'H-NMR(CDCl 3 ,TMS)6(ppm):2.21(3H,s),3.50(3H,s), 4 .08( 2 H,s), 7 .02(lH,s),7.34-7.40(3H,m),7.86(lH,dd,J=8Hz,2Hz),8.44(lHdd, J=5Hz,2Hz),8.57(lH, d,J=5Hz),8.85(lH,d,J=5Hz),9.58(lH,s). Preparation Example 221 10 According to the same manner as that of Preparation Example 34, 2-fluoroethyl chloroformate was used in place of methyl chloroformate to obtain the present compound (221) of the formula: Br 0 H 3 C CI NH NN N H (221) H -N OCH 2

CH

2 F CI 0 N r N H 0 15 The present compound (221) H-NMR(DMSO-d6,TMS)5(ppm):2.13(3H,s),4.20-4.

3 4( 2 H,m), 4 .5 3 4

.

7 0(2H,m),7.35(lH,s),7.39(lH,s),7.55(1H,s),7.61(lH,dd, 461 J=8Hz,5Hz),8.17(lH,dd,J=8Hz,2Hz),8.50(1H,dd,J=5Hz, 2 Hz), 9.49(lH,s),10.19(1H,brs),10.24(1H,brs) Preparation Example 222 According to the same manner as that of Preparation 5 Example 122, 6,8-dibromo-2-[1-(3-chloro-2-pyridinyl)- 5 thiocyanato-1H-pyrrol-2-yl]-4H-3,1-benzoxazine-4-one was used in place of 6,8-dibromo-2-[4-bromo-1-(3-chloro-2 pyridinyl)-1H-pyrrol-2-yl]-4H-3,1-benzoxazine-4-one to obtain the present compound (222) of the formula: Br Br NC\ A N H (222) H ,.N

OCH

3 ( N H O 10 The present compound (222) 'H-NMR(DMSO-d 6 ,TMS)6(ppm):3.61(3H,s),7.10(1H,d,J= 4 Hz), 7

.

3 8 (1H,d,J=4Hz),7.59(lH,dd,J=BHz,5Hz),7.64(1H,brs),8.11(lH,d, J=2Hz),8.15(1H,dd,J=8Hz,1Hz),8.54(lH,dd,J=5Hz,1Hz), 15 9.35(1H,brs),10.14(2H,brs) Preparation Example 223 According to the same manner as that of Preparation Example 93, 4-bromo-N-[4,6-dibromo-2-(hydrazinocarbonyl) phenyl) -1- (3-chloro-2-pyridinyl) -1H-pyrrole-2-carboxamide 20 and propargyl chloroformate were used in place of 4-bromo-N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl)-1 ,462 -(3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxamide and methyl chloroformate respectively to obtain the present compound (223) of the formula: Br B Br o B Br \A N N N H (223) H -N OCH 2 C=CH C I N H O 5 The present compound (223) H-NMR(DMSO-dsdTMS)5(ppm):3.55(1H,s),4.70( 2 H,s), 7

.

30 (lH,s), 7. 4 4 (lH, d, J=1H z) , 7. 4 9 (1H, dd, J=8H z, 5H z) , 7. 64 (1H, s) , 8. 05 (1H, d, J=8Hz) ,8.11 (1H, s) ,8.43 (1H, dd, J=5Hz, 1Hz), 9.60 (1H, brs) 9.94 (1H,brs) ,10.22 (1H,brs) 10 Preparation Example 224 According to the same manner as that of Preparation Example 93, N- [4, 6-dibromo-2- (hydrazinocarbonyl) phenyl]-4, 5-dichloro-1- (3-chloro-2-pyridinyl) -1H-pyrrole-2 carboxamide and propargyl chloroformate were used in place of 15 4-bromo-N-- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl) -1 - (3-chloro-2-pyridinyl) -1H-pyrrole-2-carboxamide and methyl chloroformate respectively to obtain the present compound (224) of the formula: ,463 Br Br C1 N N H (224) CI N H -N OCH 2 C=CH N H The present compound (224) 1H-NMR(DMSO-d 6 ,TMS)5(ppm):3.55(lH,s),4.

7 1( 2 H,s), 7

.

4 4 (1H,s), 7.56-7.64(2H,m),8.10(1H,s),8.15(1H,dd,J=8Hz,1Hz),8.51(1H,dd, 5 J=5Hz,lHz),9.58(lH,brs),10.02(1H,brs),10.

23 (lH,brs) Preparation Example 225 ,A mixture of 0.10 g of 6,8-dibromo-2-{4-bromo-1-(3-chloro -2-pyridinyl)-1H-imidazol-2-yl]-4H-3,1-benzoxazine-4-one, 0.16 g of methyl carbazate and 10 ml of N,N-dimethylformamide 10 was stirred at room temperature for 1 day. The reaction mixture was poured into water, and extracted with ethyl acetate three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under 15 reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.080 g of the present compound (125) of the formula: ,464 Br Br BrBr NN N H H (225) N H -eN yOCH3 H O The present compound (225) 1H-NMR(DMSO-d,TMS)(ppm):3.63(3H,s),7.59(1H,dd,J= 8 Hz,5Hz), 7 .90(lH,s),8.04(lH,d,J=2Hz),8.11(1H,d,J=8Hz),8.

24 (lH,s), 5 8.49 (lH,d, J=5Hz),9.36(1H,brs),10.17 (lH,brs),10.27 (1H,brs) Preparation Example 226 ,According to the same manner as that of Preparation Example 122, 6,8-dibromo-2- [l-(3-chloro-2-pyridinyl)-5 methylsulfonyl-H-pyrrol-2-yl] -4H-3, 1- benzoxazine-4-one was 10 used in place of 6,8-dibromo-2-[4-bromo-l-(3-chloro-2 pyridinyl)-lH-pyrrol-2-yl)- 4 H-3,1- benzoxazine-4-one to obtain the present compound (226) of the formula: Br Br O OB H 3 C ~ N H ( 2 2 6 ) 0 N H N OCH 3 (226) C N N H O The present compound (226) 15 'H-NMR(DMSO-d 6 ,TMS)5(ppm):3.27(3H,s),3.61(3H,s),7.11(1H,d,

J=

4 Hz),7.36(1H,d,J=4Hz),7.53(1H,dd,J=8Hz,5Hz), 7 .65(lH,brs), 8 .0 4 (lH,dd,J=8Hz,2Hz),8.12(1H,d,J=2Hz),8.46(1H,dd,J=5Hz, ,465 2Hz),9.36(1H,brs),10.16(1H,brs),10.22(lH,brs) Preparation Example 227 According to the same manner as that of Preparation Example 122, 6, 8-dibromo-2- [1- (3-chloro-2-pyridinyl) -5 5 methylthio-lH-pyrrol-2-yl]-4H-3,1-benzoxazine- 4-one was used in place of 6,8-dibromo-2-[4-bromo-l-(3-chloro- 2 pyridinyl) -lH-pyrrol-2-yl] -4H-3, 1-benzoxazine-4-one to obtain the present compound (227) of the formula: Br Br O / r

H

3 CS ,N N H (227) C1 N H N I OCH3 H 6 10 The present compound (227) 1 H-NMR(DMSO-d,TMS)5(ppm) :2.25(3H,s),3.60(3H,s),6.52(1H,d, J=4Hz),7.27(1H,d,J=4Hz),7.49(1H,dd,J=8Hz,5Hz),7.

6 2 (lH,brs), 8.04(1H,dd,J=8Hz,1Hz),8.07(1H,d,J=2Hz),8.45(1H,dd,J=5Hz, 1Hz),9.34 (1H,brs),9.77 (1H,brs),10.10 (lH,brs) 15 Preparation Example 228 According to the same manner as that of Preparation Example 72, 6-chloro-2-{1-(3-chloro-2-pyridinyl)-3-1 [1,2 trifluoro-2-(trifluoromethoxy)ethoxy]-lH-pyrazol-5-yl)-8 methyl-4H-3,1-benzoxazine-4-one was used in place of 20 2-[3-bromo-l-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-8 chloro-4H-3,1-benzoxazine-4-one to obtain the present ,466 compound (228) of the formula:

F

3 C,0 HF

H

3 C F0 O O FF / N HN N H H (228) H .. -N OCH3 CI 0 ,N N H 0 The present compound (228) 'H-NMR(DMSO-ds,TMS)5(ppm):2.16(3H,s), 3

.

62

(

3 H,brs), 5 7.20 (1H, s) ,7.37 (1H, dt, J=51Hz, 4Hz) , 7.38 (1H, s) ,7.55 (1 , s) , 7.61(lH,dd,J=BHz,5Hz),8.17(1H,d,J=8Hz),8.50(1H,d,J=5Hz), 9.32(1H,s),10.16(lH,s),10.30(lH,s) Preparation Example 229 According to the same manner as that of Preparation 10 Example 114, 6-chloro-2-{1- (3-chloro-2-pyridinyl)-3-[,1,2 trifluoro-2-(trifluoromethoxy)ethoxy]-1H-pyrazol-5-yl)-8 methyl-4H-3,1-benzoxazine-4-one was used in place of 2-[3 bromo-l-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl)-6-chloro-8 -methyl-4H-3,1-benzoxazine-4-one to obtain the present 15 compound (229) of the formula:

F

3 C, HF

H

3 C 0 0 FF N'N N CH 3 H(29) H -N OCH3 C1, 0 N N Hy H p The present compound (229) 467 'H-NMR(DMSO-d6,TMS))6(ppm):2.22(3H,),2.91(3H,s),3.47- 3

.

68 (3H,brm),7.24(1H,s),7.31(1H,s),7.37(1H,dt,J*51Hz,4Hz),7.

57 (lH,d,J=2Hz),7.61(lH,dd,J=8Hz,5Hz),8.17(1H,dd,J=8Hz,lHz), 8.48(1H,dd,J=5Hz,lHz),10.32(lH,s),10.

53 (lH,s) 5 Preparation Example 230 According to the same manner as that of Preparation Example 72, 6-chloro-2-[-(3-chloro-2-pyridinyl)-3 (trifluoromethylthio)-lH-pyrazol-5-yl)-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 2- [3-bromo-1- (3-chloro 10 2-pyridinyl)-1H-pyrazol-5-yl]-8-chloro-4H-3,1-benzoxazine 4-one to obtain the present compound (230) of the formula:

H

3 C C1

F

3 C-S o 'N N H (230) H N OCH 3 N H O The present compound (230) 1H-NMR(DMSO-d 6 ,TMS)(ppm):2.15(3H,s),3.62(3H,brs), 7

.

39 (1H, 15 brs), 7 .55(lH,s),7.62-7.68(2H,m),8.20(lH,dd,J=8Hz,2Hz),8.52 (lH,dd,J=5Hz,2Hz),9.32(1H,brs),10.16(lH,brs),10.36(1H,brs) Preparation Example 231 A mixture of 0.50 g of 3-bromo-N [4,6-dichloro-2-(N,N'-dimethylhydrazinocarbonyl)phenyl]-1 20 (3-chloro-2- pyridinyl)-1H-pyrazole-5-carboxamide, 0.18 g of methyl chloroformate, 0.16 g of pyridine and 10 ml of 468 acetonitrile were mixed under ice-cooling, and the mixture was stirred for 3.5 hours under ice-cooling. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water' 5 and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was washed with a mixture of methyl tert-butyl ether and hexane to obtain 0.47 g of the present compound (231) of the formula: Br 0C1 C1 Br O 'N N

CH

3 (231) H -N OCH 3 C1 O N" N H 3 C 0 10 The present compound (231) 1H-NMR(DMSO-dd 6 ,TMS)5(ppm):2.73(1.4H,s),2.83(1.

6 H,s), 2

.

95 (1.6H,s),3.07(1.4H,s),3.49-3.68(3.0H,m),7.32-7.4 4

(

2 .OH,m), 7.62(1.OH,dd,J=8Hz,5Hz),7.85(0.5H,d,J=2Hz'), 7

.

92 (0.5H,s), 15 8.19(1.OH,dd,J=8Hz,1Hz),8.49-8.52(1.OH,m),10.53(0.5H,s), 10.71 (0.5H,s) Then, examples of preparation methods for intermediate compounds used in Preparation Examples will be shown in 20 Reference Preparation Examples. Reference Preparation Example 1 A mixture of 0.44 g of 6-chloro-2-[1-(3-chloro-2- .469 pyridinyl)-3-trifluoromethyl-1H-pyrazol- 5 -yl]-8-methyl-4H-3 ,1-benzoxazine-4-one, 0.05 g of hydrazine monohydrate and 10 ml of tetrahydrofuran was stirred at room temperature for 2 hours. After the reaction mixture was mixed with water and 5 ethyl acetate, layers were separated. The organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.10 g of N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl) -1- (3 10 chloro-2-pyridinyl)-3-trifluoromethyl-lH-pyrazole-5 carboxamide of the formula:

H

3 C C1

F

3 C N I N N H

-NH

2 Ci O N N H N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyll -1- (3-chlo ro-2-pyridinyl) -3-trifluoromethyl-1H-pyrazole-5-carboxamide 15 1 H-NMR (DMSO-dr>,TMS) 5 (ppm): 2.16 (3H, s), 4.36 (2H, s), 7.32 (1H, s), 7.48 (1H, s), 7.66 (1H, dd, J=4Hz, 8Hz), 7.74 (lH, s), 8.22 (lH, d, J=8Hz), 8.54 (lH, d, J=4Hz), 9.56 (1H, brs), 10.39 (lH, brs). Reference Preparation Example 2 20 A mixture of 0.44 g of 6-chloro-2-[l-(3-chloro-2 pyridinyl)-3-trifluoromethyl-H-pyrazol-5-yl]-8-methyl-4H-3 .470 ,1-benzoxazine-4-one, 0.05 g of methylhydrazine and 10 ml of tetrahydrofuran was stirred at room temperature for 2 hours. After the reaction mixture was mixed with water and ethyl acetate, layers were separated. The organic layer was washed 5 with water, dried over 'sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.40 g of N-[4-chloro-2-(N-methylhydrazinocarbonyl)-6-methylphenyl]-1 - (3-chloro-2-pyridinyl) -3-trifluoromethyl-1H-pyrazole-5 10 carboxamide of the formula:

H

3 C C1

F

3 C O /C NSI N, %N H

,NH

2 Ci O N "N CH 3 N- [4-chloro-2- (N-methylhydrazinocarbonyl) -6-methylphenyl] -1 - (3-chloro-2-pyridinyl) -3-trifluoromethyl-lH-pyrazole-5 carboxamide 15 'H-NMR (DMSO-d 6 ,TMS) & (ppm): 2.17 (1.8H, s), 2.30 (1.2H, s), 2.76 (1.2H, s), 3.05 (1.8H, s), 4.54 (1.2H, brs), 4.99 (0.8H, brs), 7.16-7.23 (lH, m), 7.36 (0.6H, s), 7.46 (0.4H, s), 7.66-7.70 (2H, m), 8.24 (1H, d, J=8Hz), 8.54 (1H, d, J=4Hz), 10.25 (0.6H, brs), 10.51 (0.4H, brs). 20 Reference Preparation Example 3 A mixture of 0.40 g of 2-[1-(3-chloro-2-pyridinyl)-3- 471 trifluoromethyl-1H-pyrazol-5-yl]-8-methyl-4H-3,1 benzoxazine-4-one, 0.09 ml of hydrazine monohydrate and 20 ml of tetrahydrofuran was stirred at room temperature for 3 hours. Water was poured into the reaction mixture, and the mixture was' 5 extracted with ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 0.26 g of 1-(3-chloro-2-pyridinyl)-N-[2-(hydrazinocarbonyl)-6 10 methylphenyl)-3-trifluoromethyl-1H-pyrazole-5-carboxamide of the formula:

H

3 C

F

3 C N N H

-NH

2 CI 0 N 'N H 1-(3-Chloro-2-pyridinyl)-N-[2-(hydrazinocarbonyl)-6 methylphenyl]-3-trifluoromethyl-1H-pyrazole-5-carboxamide 15 1 H-NMR (CDCl 3 ,TMS) 6 (ppm): 2.22 (3H, s), 4.05 (2H, s), 7.18-7.40 (5H, m), 7.42 (1H, dd, J=8Hz, 4Hz), 7.89 (1H, dd, J=8Hz, 1Hz), 8.48 (1H, dd, J=4Hz, 1Hz), 10.04 (1H, s). Reference Preparation Example 4 A mixture of 0.27 g of 8-chloro-2-[1-(3-chloro-2 20 pyridinyl)-3-trifluoromethyl-1H-pyrazol-5-yl]- 4 H-3,1 benzoxazine-4-one, 0.025 ml of hydrazine monohydrate and 10 ml .472 N of tetrahydrofuran was stirred at room temperature for 3 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride 5 solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was washed with a mixed solvent of chloroform and methyl t-butyl ether to obtain 0.21 g of N-[2-chloro-6-(hydrazinocarbonyl) phenyl] -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl-lH 10 pyrazole-5-carboxamide of the formula: CI

F

3 C N Cl N N HH CI NN 0 N N- [2-chloro-6- (hydrazinocarbonyl) phenyl] -l- (3-chloro-2 pyridinyl) -3-trifluoromethyl-1H-pyrazole-5-carboxamide 'H-NMR (DMSO-d 6 ) 5 (ppm): 4.35 (2H, brs), 7.38-7.39 (2H, m), 15 7.61-7.66 (2H, m), 7.79 (lH, s), 8.20 (1H, d, J=8Hz), 8.53 (1H, d, J=4Hz), 9.52 (1H, s), 10.04 (1H, s). Reference Preparation Example 5 A mixture of 0.40 g of 2-[3-bromo-1-(3-chloro-2 pyridinyl)-1H-pyrazol-5-yl]-6-chloro-8-methyl-4H- 3 ,1 20 benzoxazine-4-one, 0.08 ml of hydrazine monohydrate and 10 ml of tetrahydrofuran was stirred at room temperature for 3 hours.

473 The reaction mixture was poured into water and then filtered. The resulting filter cake was washed with water and methyl tert-butyl ether. The filter cake was dissolved in ethyl acetate, dried over anhydrous magnesium sulfate, and 5 concentrated under reduced pressure to obtain 0.35 g of 3-bromo-N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl] -1 -(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide of the formula:

H

3 C C1 BrN N N H -NH2 C1 O N N H 10 3-Bromo-N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl]-1 -(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide 'H-NMR (DMSO-d 6 ) 6 (ppm): 2.14 (3H, s), 4.37 (2H, brs), 7.31 (1H, s), 7.38 (1H, s), 7.47 (1H, s), 7.61 (1H, dd, J=8Hz, 4Hz), 8.17 (1H, dd, J=8Hz, 1Hz), 8.50 (1H, dd, J=4Hz, 1Hz), 9.55 (1H, 15 brs), 10.26 (1H, brs). Reference Preparation Example 6 A mixture of 0.88 g of 6-chloro-2-[1-(2-chlorophenyl)-3 trifluoromethyl-1H-pyrazol-5-yl)-8-methyl-4H-3,1 benzoxazine-4-one, 0.19 ml of hydrazine monohydrate and 3 ml 20 of tetrahydrofuran was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and the mixture was 474 extracted with ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 0.94 g of 5 N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl]-l-( 2 chlorophenyl) -3-trifluoromethyl-1H-pyrazole-5-carboxamide of the formula: F ~H3C ' 1

F

3 C O / C 'N N N H9 , NH2 H

I.-.

N- [4-chloro-2- (hydrazinocarbonyl) -6-methyiphenyll --(2 10 chlorophenyl) -3-trifluoromethyl-1H-pyrazole-5-carboxamide 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 2.18 (3H, s), 4.03 (2H, brs), 7.19-7.54 (8H, m), 9.74 (1H, s). Reference Preparation Example 7 A mixture of 0.50 g of 6-chloro-2-[1-(3-chloro-2 15 pyridinyl)-1H-pyrazol-5-yl]-8-methyl- 4 H-3,1-benzoxazine-4 one, 0.13 ml of hydrazine monohydrate and 20 ml of tetrahydrofuran was stirred at room temperature for 4 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate two times. The organic layers were 20 combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and ,475 concentrated under reduced pressure. The resulting residue was washed with a mixed solvent of ethyl acetate and hexane to obtain 0.44 g of N-[4-chloro-2-(hydrazinocarbonyl)-6 methylphenyl) -1- (3-chloro-2-pyridinyl) -1H-pyrazole-5- 5 carboxamide of the formula:

H

3 C C1 0 / N N N H ,NH2 C N H N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl) -1- (3 chloro-2-pyridinyl) -lH-pyrazole-5-carboxamide 'H-NMR (CDCl,TMS) 6 (ppm): 2.19 (3H, s), 4.03 (2H, brs), 7.05 10 (1H, d, J=2Hz), 7.19 (1H, d, J=2Hz), 7.36 (1H, dd, J=8Hz, 4Hz), 7.50 (1H, s), 7.83-7.86 (2H, m), 8.46 (1H, dd, J=4Hz, 1Hz), 9.64 (1H, s). Reference Preparation Example 8 To a solution of 3.1 g of 1-(3-chloro-2-pyridinyl)- 3 15 trifluoromethyl-lH-pyrazole-5-carbonyl chloride in 100 ml of acetonitrile, 1.9 g of 2-amino-5-chloro-3-methylbenzoic acid was added. The mixture was stirred at room temperature for 10 minutes and then, 1.0 g of triethylamine was added thereto. The mixture was stirred at room temperature for 20 minutes and then, 20 2.0 g of triethylamine was further added thereto. After the mixture was stirred at room temperature for 20 minutes, 1.2 g ,476 of methanesulfonyl chloride was added and the mixture was stirred at room temperature for 3 hours. After the reaction mixture was concentrated under reduced pressure, ethyl acetate and water were poured into the residue to separate layers. The' 5 organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressured. The resulting residue was subjected to silica gel column chromatography to obtain 4.2 g of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-lH-pyrazol-5-yl -8-methyl-4H-3, 1 10 benzoxazine-4-one of the formula:

F

3 C ' N, 0 0 Cl N / ;\ ci N

H

3 C 6-Chloro-2- [1- (3-chloro-2-pyridinyl) -3-trifluoromethyl-1H pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine-4-one 1 H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.73 (3H, s), 7.80 (lH, s), 7.82 15 (1H, dd, J=4Hz, 8Hz), 7.90 (1H, s), 7.91 (1H, s), 8.39 (1H, d, J=8Hz), 8.66 (1H, d, J=4Hz). Reference Preparation Example 9 To a solution of 2.0 g of 1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-1H-pyrazole-5-carbonyl chloride in 50 ml of 20 acetonitrile, 0.98 g of 2-amino-3-methylbenzoic acid was added. The mixture was stirred at room temperature for 10 minutes and .477 then, 0.9 ml of triethylamine was added thereto. The mixture was stirred at room temperature for 20 minutes and then, 1.8 ml of triethylamine was further added thereto. After the mixture was stirred at room temperature for 20 minutes, 0.56 5 ml of methanesulfonyl chloride was added and the mixture was stirred at room temperature for 3 hours. Water was poured into the reaction'mixture, and the mixture was extracted with ethyl acetate two times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over 10 anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 1.17 g of 2-[l-(3-chloro-2 pyridinyl)-3-trifluoromethyl-1H-pyrazol-5-yl]-8-methyl-4H-3 ,1-benzoxazine-4-one of the formula:

F

3 C N, C1 N - 15

H

3 C 2-[1-(3-Chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazol- 5 yl]-8-methyl-4H-3,1-benzoxazine-4-one 1 H-NMR (CDC1 3 ,TMS) 6 (ppm): 1.84 (3H, s), 7.39 (1H, t, J=8Hz), 7.50-7.55 (3H, m), 7.99 (1H, dd, J=8Hz, 1Hz), 8.01 (lH, d, 20 J=8Hz), 8.59 (1H, dd, J=4.5Hz, 1Hz). Reference Preparation Example 10 .478 To a solution of 0.80 g of 1-(3-chloro-2-pyridinyl)- 3 trifluoromethyl-1H-pyrazole-5-carbonyl chloride in 20 ml of acetonitrile, 0.44 g of 2-amino-3-chlorobenzoic acid was added. The mixture was stirred at room temperature for 10 minutes-and 5 then, 0.36 ml of triethylamine was added thereto. The mixture was stirred at room temperature for 20 minutes and then, 0.72 ml of triethylamine was further added thereto. After the mixture was stirred at room temperature for 20 minutes, 0.22 ml of methanesulfonyl chloride was added and the mixture was 10 stirred at room temperature for 20 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate two times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced 15 pressure. The resulting residue was subjected to silica gel column chromatography to obtain 1.17 g of 8-chloro-2-(1-(3 chloro-2-pyridinyl) -3-trifluoromethyl-1H-pyrazol-5-yl) -4H-3 ,1-benzoxazine-4-one of the formula:

F

3 C C , N / Ct ~N C. 20 8-Chloro-2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H pyrazol-5-yl]-4H-3,1-benzoxazine-4-one 1 H-NMR (CDCl 3 ,TMS) 6 (ppm): 7.43 (1H, t, J=8Hz), 7.52 (1H, dd, ,479 J=8Hz, 4Hz), 7.53 (1H, s), 7.75 (1H, dd, J=8Hz, 1Hz), 8.00 (1H, dd, J=8Hz, 1Hz), 8.11 (1H, dd, J=8Hz, 1Hz), 8.57 (1H, dd, J=4Hz, 1Hz) Reference Preparation Example 11 5 To a mixture of 0,.44 g of 3-bromo-1-(3-chloro-2 pyridinyl)-1H-pyrazole-5-carboxylic acid, 6 ml of acetonitrile and 0.20 g of triethylamine was added 0.125 ml of methanesulfonyl chloride. After the resulting mixture was stirred at room temperature for 15 minutes, 0.27 g of 10 2-amino-5-chloro-3-methylbenzoic acid was added and the mixture was stirred at room temperature for 20 minutes. To the mixture, 0.40 ml of triethylamine was added. After the mixture was stirred at room temperature for 20 minutes, 0.13 ml of methanesulfonyl chloride was added and the mixture was stirred 15 at room temperature for 16 hours. The reaction mixture was filtered and the filter cake was washed with methyl tert-butyl ether. The resulting filter cake was dissolved in ethyl acetate, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and 20 concentrated under reduced pressure to obtain 0.098 g of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl)-6-chlo ro-8-methyl-4H-3,1-benzoxazine-4-one. In addition, the filtrate was concentrated under reduced pressure, and the resulting residue was subjected to silica gel column 25 chromatography to obtain 0.093 g of ,480 2-[3-bromo-1-(3-chloro-2-pyridinyl) 1H-pyrazol-5-yl)-6-chloro-8-methyl-4H-3,1-benzoxazine-4-one of the formula: Br N O O 'N C1 NN c

H

3 C 5 2-[3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6 chloro-8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.81 (3H, s), 7.25 (1H, s), 7.48-7.51 (2H, m), 7.95-7.98 (2H, m), 8.56 (1H, dd, J=4Hz, 1Hz) Reference Preparation Example 12 10 To a mixture of 1.0 g of 1-(2-chlorophenyl)-3 trifluoromethyl-1H-pyrazole-5-carbonyl chloride and 10 ml of acetonitrile was added 0.60 g of 2-amino-5-chloro-3 methylbenzoic acid, and the resulting mixture was stirred at room temperature for 10 minutes. To the mixture, 0.46 ml of 15 triethylamine was added. After the mixture was stirred at room temperature for 20 minutes, 0.92 ml of triethylamine was further added thereto. After the mixture was stirred at room temperature for 20 minutes, 0.28 ml of methanesulfonyl chloride was added thereto and the mixture was stirred at room 20 temperature for 3 hours. The reaction mixture was filtered, and the resulting filtrate was concentrated under reduced pressure. The resulting residue was subjected to silica gel ,481 column chromatography to obtain 0.98 g of 6-chloro-2--[l-( 2 chlorophenyl)-3-trifluoromethyl-1H-pyrazol-5-yl]-8-methyl-4 H-3,1-benzoxazine-4-one of the formula:

F

3 C N, 0 0 'N CI N

H

3 C 5 6-chloro-2-[1-(2-chlorophenyl)-3-trifluoromethyl-1H pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine-4-one H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.82 (3H, s), 7.45-7.60 (6H, m), 7.99 (1H, s). Reference Preparation Example 13 10 A mixture of 1.22 g of 1-(3-chloro-2-pyridinyl)-1H pyrazole-5-carboxylic acid and 1.15 ml of thionyl chloride was heated to reflux for 2 hours. The reaction mixture was allowed to cool to room temperature and then concentrated under reduced pressure. The resulting residue was dissolved in 15 ml of 15 acetonitrile, and 0.27 g of 2-amino-5-chloro-3-methylbenzoic acid was added thereto. The mixture was stirred at room temperature for 10 minutes. To the mixture was added 0.73 ml of triethylamine, and the mixture was stirred at room temperature for 20 minutes. Thereto 1.45 ml of triethylamine 20 was further added, and the mixture was stirred at room temperature for 20 minutes. Then 0.44 ml of methanesulfonyl .482 chloride was added, and the mixture was stirred at room temperature for 3 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate two times. The organic layers were combined, washed with an aqueous 5 saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was washed with methyl tert-butyl ether to obtain 0.68 g of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-1H pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine- 4 -one of the 10 formula: 'N

H

3 C CI 6-Chloro-2-[1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-8 methyl-4H-3,1-benzoxazine-4-one 'H-NMR (CDC1 3 ,TMS) 6 (ppm): 1.82 (3H, s), 7.28 (1H, d, J=2Hz), 15 7.46-7.49 (2H, m), 7.91 (1H, d, J=2Hz), 7.95-7.99 (2H, m), 8.57 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 14 A mixture of 15.30 g of 3-trifluoromethyl-1H-pyrazole, 16.64 g of 2,3-dichloropyridine, 26.42 g of potassium carbonate 20 and 100 ml of N,N-dimethylformamide was stirred at 130*C for 14 hours. The reaction mixture was allowed to cool to room temperature and then water was poured thereto. The mixture was .483 extracted with ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The 5 resulting residue was .subjected to silica gel column chromatography to obtain 22.88 g of 3-chloro-2-(3-trifluoromethyl-1H-pyrazol -1-yl)pyridine of the formula:

F

3 C N 'N Cl N 10 3-Chloro-2- (3-trifluoromethyl-lH-pyrazol-1-yl)pyridine 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 6.75 (lH, d, J=2Hz), 7.37 (1H, dd, J=8Hz, 4Hz), 7.95 (lH, dd, J=8Hz, 1Hz), 8.14 (1H, d, J=lHz), 8.49 (lH, dd, J=4Hz, 1Hz). Reference Preparation Example 15 15 To a mixture of 15 g of 3-chloro-2-(3-trifluoromethyl 1H-pyrazol-1-yl)pyridine and 150 ml of tetrahydrofuran was added dropwise 39 ml of a 2.0 mol/L lithium diisopropylamide solution in heptane/tetrahydrofuran/ethylbenzene at -78*C, and then stirred at -78*C for 15 minutes. Carbon dioxide was 20 introduced into the mixture at such a rate that the inner temperature was retained at -60 0 C or lower. After the mixture turned yellow, it was further stirred at -78*C for 10 minutes.

484 After the temperature of the reaction mixture was allowed to rise to room temperature, 200 ml of water and 200 ml of hexane were poured. The aqueous layer was adjusted to pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution and then' 5 layers were separated. The organic layer was extracted with a 0.5N aqueous sodium hydroxide solution. The aqueous layers were combined, washed with diethyl ether, adjusted to around pH 3 by an addition of 2N hydrochloric acid, and then extracted with methyl tert-butyl ether three times. The organic layers 10 were combined, washed with an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 16.08 g of 1-(3-chloro-2-pyridinyl) -3-trifluoromethyl-1H-pyrazole-5-carboxylic acid of the formula:

F

3 C ClN 15 1- (3-Chloro-2-pyridinyl) -3-trifluoromethyl-lH-pyrazole-5 carboxylic acid 'H-NMR (DMSO-d 6 ) 5 (ppm): 7.60 (1H, s), 7.74 (lH, dd, J=8Hz, 4Hz), 8.30 (lH, dd, J=8Hz, 1Hz), 8.60 (lH, dd, J=4Hz, 1Hz). 20 Reference Preparation Example 16 A mixture of 16.08 g of 1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-lH-pyrazole-5-carboxylic acid and 12 ml of 485 , thionyl chloride was heated to reflux for 2 hours. The reaction mixture was allowed to cool to room temperature and subjected to distillation under reduced pressure (125*C/3mmHg) to obtain 14.2 g of 1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-lH 5 pyrazole-5-carbonyl chloride of the formula:

F

3 C N'N COCI CIN 1- (3-Chloro-2-pyridinyl) -3-trifluoromethyl-lH-pyrazole-5 carbonyl chloride 'H-NMR (CDCl 3 ,TMS) 5 (ppm): 7.,52 (1H, s), 7.52 (1H, dd, J=8Hz, 10 4Hz), 7.97 (1H, dd, J=8Hz, 1Hz), 8.53 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 17 To a mixture of 18 g of 4-ethoxy-1, 1, 1-trifluoro-3-butene -2-one and 50 ml of methanol was added 5.7 ml of methylhydrazine, and the mixture was heated to 'reflux for 4 hours. The reaction 15 mixture was allowed to cool to room temperature, concentrated under reduced pressure, and subjected to distillation under reduced pressure (60*C/15 mmHg) to obtain 8.71 g of 1-methyl-3-trifluoromethyl-1H-pyrazole of the formula:

F

3 C N

CH

3 . 20 1-Methyl-3-trifluoromethyl-1H-pyrazole 486 1H-NMR (CDCl 3 ,TMS) 5 (ppm): 3.97 (3H, s), 6.51 (1H, d, J=2Hz), 7.40 (1H, d, J=2Hz). Reference Preparation Example 18 To a mixture of 8.71 g of 1-methyl-3-trifluoromethyl-1H-' 5 pyrazole and 130 ml of tetrahydrofuran was added dropwise 32 ml of a 2.0 mol/L lithium diisopropylamide solution in heptane/tetrahydrofuran/ethylbenzene at -78*C. The mixture of stirred at -78 0 C for 2 hours and then poured into a mixture was dry ice and 50 ml of tetrahydrofuran. The mixture was stirred 10 for 2 hours while allowing it to rise to around room temperature. Water, and diethyl ether were poured into the reaction mixture. The aqueous layer was adjusted to pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution, and then layers were separated. The resulting aqueous layer was washed with diethyl 15 ether two times, adjusted to around pH 3 by an addition of 2N hydrochloric acid, and then extracted with methyl tert-butyl ether three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to 20 obtain 8.19 g of 1-methyl-3 trifluoromethyl-1H-pyrazole-5-carboxylic acid of the formula:

F

3 C 'N CO 2 H CH3 1-Methyl-3-trifluoromethyl-lH-pyrazole-5-carboxylic acid .487 1 H-NMR (CDCl 3 ,TMS) 6 (ppm): 4.13 (3H, s), 7.22 (1H, s). Reference Preparation Example 19 To a mixture of 15 g of pyrazole and 200 ml of toluene was added dropwise 23.7 ml of dimethylsulfamoyl chloride at rooni 5 temperature. Then, 40 ml of triethylamine was added to the mixture, and the mixture was stirred at room temperature for 18 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 10 17.6 g of N,N-dimethyl-lH-pyrazole-l-sulfonamide of the formula: N

SO

2

N(CH

3

)

2 . N,N-dimethyl-lH-pyrazole-1-sulfonamide H-NMR (CDCl 3 ,TMS) 6 (ppm): 2.95 (6H, s), 6.40 (1H, dd, J=2Hz, 15 J=lHz), 7.75 (1H, d, J=lHz), 7.95 (1H, d, J=2Hz,). Reference Preparation Example 20 To a mixture of 17.6 g of N,N-dimethyl-lH-pyrazole-l sulfonamide and 200 ml of tetrahydrofuran was added dropwise 80 ml of a 1.3M solution of n-butyl lithium in hexane at -78 0 C, 20 and the resulting mixture was stirred at -78 0 C for 15 minutes. To the mixture, a solution of 35.8 g of 1,2-dibromo-1,1,2,2 tetrachloroethane in 60 ml of tetrahydrofuran was added dropwise, and the resulting mixture was stirred at -78 0 C for , 488 15 minutes. The reaction mixture was returned to room temperature, and stirred for 1 hour. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed 5 with an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 21.3 g of 5-bromo-N,N-dimethyl-lH pyrazole-1-sulfonamide of the formula: N75 Br S'N 10 SO 2

N(CH

3

)

2 . 5-Bromo-N,N-dimethyl-1H-pyrazole-l-sulfonamide 'H-NMR (CDCl,,TMS) 5 (ppm): 3.08 (6H, s), 6.43 (1H, m), 7.61 (lH, m). Reference Preparation Example 21 15 A mixture of 21.3 g of 5-bromo-N,N-dimethyl-1H-pyrazole 1-sulfonamide and 30 ml of trifluoroacetic acid was stirred at room temperature for 2 hours. After hexane was poured into the reaction mixture, the mixture was filtered. After methyl tert-butyl ether was added to the resulting filtrate, the 20 mixture was washed successively with an aqueous saturated sodium hydrogen carbonate solution, water and an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 10.7 ,489 g of 3-bromo-1H-pyrazole of the formula: Br N H. 3-Bromo-lH-pyrazole 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 6.37 (1H, d, J=2Hz), 7.55 (1H, d, 5 J=2Hz), 12.6 (lH, brs). Reference Preparation Example 22 A mixture of 10.7 g of 3-bromo-1H-pyrazole, 11.8 g of 2, 3-dichloropyridine, 57.3 g of cesium carbonate and 80 ml of N,N-dimethylformamide was stirred at 100*C for 8 hours. The 10 reaction mixture was allowed to cool to room temperature, and water was poured thereto. The mixture was extracted with methyl tert-butyl ether two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and 15 concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 12.9 g of 2-(3-bromo-1H-pyrazol-1-yl)-3-chloropyridine of the formula: Br 'N 20 2-(3-Bromo-lH-pyrazole-1-yl)-3-chloropyridine .490 1 H-NMR (CDCl 3 ,TMS) 5 (ppm): 6.51 (1H, d, J=2Hz), 7.331 (1H, dd, J=8Hz, 4Hz), 7.91 (1H, dd, J=8Hz, 1Hz), 8.04 (1H, d, J=2Hz), 8.45 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 23 5 To a mixture of 9.,2 g of 2-(3-bromo-1H-pyrazol-1-yl)- 3 chloropyridine and 80 ml of tetrahydrofuran was added dropwise 21.3 ml of a 2.OM lithium diisopropylamide solution in heptane/tetrahydrofuran/ethylbenzene at -78*C. The resulting mixture was stirred at -78*C for 15 minutes, poured to a mixture 10 of dry ice and 50 ml of tetrahydrofuran, and stirred for 1 hour with allowing it to rise to around room temperature. After water and diethyl ether were poured into the reaction mixture, the aqueous layer was adjusted to pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution and layers were 15 separated. The resulting aqueous layer was washed with diethyl ether two times, adjusted to around pH 3 by an addition of 2N hydrochloric acid, and extracted with methyl tert-butyl ether three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over 20 magnesium sulfate, and concentrated under reduced pressure to obtain 7.96 g of 3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole -5-carboxylic acid of the formula: 491 Br N'N CO 2 H C1 N. N 3-Bromo-1-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid 1 H-NMR (DMSO-d 6 ) 6 (ppm): 7.25 (1H, s), 7.68 (1H, dd, J=8Hz, 5 4Hz), 8.24 (1H, dd, J=8Hz, J=lHz), 8.56 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 24 To a mixture of 12.96 g of 4,4,4-trifluoro-1-(2-furyl) 1,3-butanedione, 8.56 g of sodium acetate and 40 ml of acetic acid was added 11.26 g of 2-chlorophenylhydrazine 10 hydrochloride at room temperature. The mixture was stirred at 60*C for 1 hour, and concentrated under reduced pressure. After the reaction mixture was concentrated under reduced pressure and water was poured into the residue, the mixture was extracted with chloroform three times. The organic layers were combined, 15 washed with an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 18.43 g of 1- (2-chlorophenyl) -5 20 (2-furyl)-3-trifluoromethyl-1H-pyrazole of the formula: -492

F

3 C 0 'N \ / .CI 1- (2-Chlorophenyl) -5- (-2-furyl) -3-trifluoromethyl-1H pyrazole 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 5.76 (1H, d, J=3Hz), 6.31 (1H, dd, 5 J=3Hz, 2Hz), 6.95 (1H, s), 7.40 (1H, d, J=2Hz), 7.43-7.59 (4H, M). Reference Preparation Example 25 ,An aqueous solution of 27.94 g of potassium permanganate in 100 ml of water was added dropwise to a mixture of 18.43 g 10 of 1-(2-chlorophenyl) -5- (2-furyl)-3-trifluoromethyl-lH pyrazole and 250 ml of acetone with being kept at 40 0 C or lower. Then, the mixture was stirred at room temperature for 20 hours. The reaction mixture was filtered through Celite (registered trademark) to obtain a filtrate. The filtrate was adjusted to 15 pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution, and then extracted with ethyl acetate two times. The aqueous layer was adjusted to around pH 3 by an addition of 2 N hydrochloric acid, and then extracted with methyl tert-butyl ether three times. The organic layers were combined, washed 20 with an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 10.65 g of 1-(2-chlorophenyl)-3-trifluoromethyl-lH- .493 pyrazole-5-carboxylic acid of the formula:

F

3 C N5 'N CO 2 H CI 1-(2-Chlorophenyl)-3-trifluoromethyl-lH-pyrazole-5 carboxylic acid 5 1 H-NMR (CDC1 3 ,TMS) 5 (ppm): 7.33 (1H, s), 7.42-7.54 (4H, m). Reference Preparation Example 26 A mixture of 10.65 g of 1-(2-chlorophenyl)-3 trifluoromethyl-lH-pyrazole-5-carboxylic acid and 8 ml of thionyl chloride heated to reflux for 2 hours. The reaction 10 mixture was allowed to cool to room temperature, concentrated under reduced pressure, and subjected to distillation under reduced pressure (110*C/5 mmHg) to obtain 8.39 g of 1-(2-chlorophenyl)-3-trifluoromethyl-1H-pyrazole-5-carbonyl chloride of the formula:

F

3 C 'N COCI C1 15 1- (2-Chlorophenyl) -3-trifluoromethyl-lH-pyrazole-5-carbonyl chloride 1 H-NMR (CDCl 3 ,TMS) 5 (ppm): 7.42-7.57 (5H, m). Reference Preparation Example 27 -494 A mixture of 2 g of pyrazole, 4.34 g of 2,3-dichloropyridine, 9.58 g of cesium carbonate and 40 ml N,N-dimethylformamide was stirred at 100 0 C for 8 hours. The reaction mixture was allowed to cool to room temperature, and 5 water was added thereto. The mixture was extracted with methyl tert-butyl ether three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was 10 subjected to silica gel column chromatography to obtain 3.57 g of ,3-chloro-2-(1H-pyrazol-1-yl)pyridine of the formula: N N N C1 3-Chloro-2-(1H-pyrazole-1-yl)pyridine 1 H-NMR (CDCl 3 , TMS) 6 (ppm): 6.50 (1H, dd, J=2Hz, 1Hz), 7.28 (1H, 15 dd, J=8Hz, 4Hz) , 7.83 (1H, d, J=lHz) , 7.92 (1H, dd, J=8Hz, 1Hz) , 8.17 (lH, d, J=2Hz), 8.46 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 28 To a mixture of 2.0 g of 3-chloro-2-(lH-pyrazol-1-yl) pyridine and 100 ml of tetrahydrofuran was added dropwise 6.7 20 ml of a 2.0 mol/L lithium diisopropylamide solution in heptane/tetrahydrofuran/ethylbenzene at -78*C. The mixture was stirred at -78"C for 10 minutes, poured into a mixture of 495 dry ice and 50 ml of tetrahydrofuran, and stirred for 0.5 hour with allowing it to rise to around room temperature. After water and diethyl ether were added to the reaction mixture, the aqueous layer was adjusted to pH 10-12 by an addition of a 2N 5 aqueous sodium hydroxide solution and layers were separated. After the aqueous layer was washed with diethyl ether two times, the aqueous layer was adjusted to around pH 3 by an addition of 2N hydrochloric acid, and the mixture was extracted with methyl tert-butyl ether three times. The organic layers were 10 combined, washed with an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 1. 22 g of 1- (3-chloro-2-pyridinyl)-lH- pyrazole-5-carboxylic acid of the formula: IN HO2C N' N C 15 1-(3-Chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid H-NMR (CDC1 3 ,TMS) 5 (ppm): 7.10 (lH, d, J=2Hz), 7.42 (1H, dd, J=8Hz, 4Hz), 7.82 (lH, d, J=2Hz), 7.91 (lH, dd, J=8Hz, 1Hz), 8.51 (lH, dd, J=4Hz, 1Hz). 20 Reference Preparation Example 29 A mixture of 16.3 g of isatoic anhydride, 10.4 g of ethyl carbazate and 50 ml of ethanol was heated to reflux for 3 hours.

496 After the reaction mixture was allowed to cool to around room temperature, ethyl acetate was added thereto and the mixture was washed with water two times. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced 5 pressure. The resulting residue was washed with methyl tert-butyl ether to obtain 14.9 g of N-(2-aminobenzoyl) N'-ethoxycarbonylhydrazine of the formula:

H

2 N

CONHNHCO

2

CH

2

CH

3 N- (2-aminobenzoyl) -N' -ethoxycarbonylhydrazine 10 1H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.28 (3H, t, J=8Hz), 4.22 (2H, q, J=8Hz), 5.45 (2H, brs), 6.63-6.68 (2H, m), 6.85 (1H, brs), 7.22 (lH, brs), 7.43 (1H, d, J=8Hz), 7.95 (1H, brs). Reference Preparation Example 30 A mixture of 8.86 g of N-methylisatoic anhydride, 5.73 g 15 of ethyl carbazate and 25 ml of ethanol was heated to reflux for 2 hours. After the reaction mixture was allowed to around room temperature, ethyl acetate was added thereto and the mixture was washed with water two times. The organic layer was dried over anhydrous sodium sulfate, and concentrated under 20 reduced pressure. The resulting residue was washed with methyl tert-butyl ether to obtain 5. 99 g of N- (2-methylaminobenzoyl) N'-ethoxycarbonylhydrazine of the formula: 497

H

3C'N H CONHNHCO 2

CH

2

CH

3 N-(2-methylaminobenzoyl)-N'-ethoxycarbonylhydrazine 1 H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.28 (3H, t, J=7Hz), 2.85 (3H, d, J=5Hz), 4.21 (2H, q, J=7Hz), 6.55-6.59 (1H, m), 6.66 (1H, d, 5 J=8Hz), 6.78'(1H, brs), 7.29-7.37 (2H, m), 7.43 (1H, dd, J=8Hz, 1Hz), 7.91 (1H,, brs). Reference Preparation Example 31-(1) A mixture of 1.0 g of 1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-lH-pyrazole-5-carboxylic acid and 2 ml of 10 thionyl chloride was heated to ref lux for 2 hours. The reaction mixture was allowed to cool to room temperature, and concentrated under reduced pressure. The resulting residue was dissolved in 15 ml of acetonitrile, and 0.49 g of 2-amino 3,5-dimethylbenzoic acid was added thereto. The mixture was 15 stirred at room temperature for 30 minutes. To the mixture, 0.7 ml of triethylamine was added, and the mixture was, stirred at room temperature for 30 minutes. Further 1.4 ml of triethylamine was added, and the mixture was stirred at room temperature for 30 minutes. Then 0.5 ml of methanesulfonyl 20 chloride was added, and the mixture was stirred at room temperature for 5 hours. Water was poured into the reaction mixture, and the mixture was concentrated under reduced pressure. The resulting residue was washed with water and 498 ' methyl tert-butyl ether to obtain 0.71 g of 2-[1-(3-chloro-2 pyridinyl)-3-trifluoromethyl-1H-pyrazol-5-yl)-6,8-dimethyl 4H-3,1-benzoxazine-4-one of the formula:

F

3 0 CIN N 3 C CH 3 . 5 2-[l-(3-Chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazole-5 -yl]-6,8-dimethyl-4H-3,1-benzoxazine-4-one 1H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 1.72 (3H, s), 2.37 (3H, s), 7.54 (1H, s), 7.77 (1H, s), 7.78-7.85 (2H, m), 8.39 (1H, d, J=8Hz), 8.66 (1H, d, J=4Hz). 10 Reference Preparation Example 31-(2) According to the same manner as that of Reference Preparation Example 1, 2- [1- (3-chloro-2-pyridinyl) -3 trifluoromethyl-1H-pyrazol-5-yl]-6,8-dimethyl-4H-3,1-benzox azine-4-one was used in place of 6-chloro-2-[l-(3-chloro-2 15 pyridinyl)-3-trifluoromethyl-1H-pyrazol-5-yl)-8-methyl-4H-3 ,1-benzoxazine-4-one to obtain N-[4,6-dimethyl-2 (hydrazinocarbonyl)phenyl]-1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-lH-pyrazole-5-carboxamide of the formula:

F

3 C 8 3 C . CH 3 N, N N H H Ci 0 N0 N H 499 N-[4,6-dimethyl-2-(hydrazinocarbonyl)phenyl]-1-(3-chloro-2 pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carboxamide 'H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 2.11 (3H, s), 2.27 (3H, s), 4.34 (2H, brs), 7.11 (1H, s), 7.17 (1H, s), 7.66 (1H, dd, J=8Hz, 4Hz), 5 7.74 (1H, s), 8.21 (1H,; d, J=8Hz), 8.53 (1H, d, J=4Hz), 9.37 (1H, brs), 10.26 (1H, brs). Reference Preparation Example 32-(1) According to the same manner as that of Reference Preparation Example 31- (1), 2-amino-3-bromo-5-methylbenzoic 10 acid was used in place of 2-amino-3,5-dimethylbenzoic acid to obtain 8-bromo-2-[1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-1H-pyrazol-5-yl) -6-methyl-4H-3, 1 benzoxazine-4-one of the formula:

F

3 C N 0 0 N cI N Br

CH

3 . 15 8-Bromo-2-[l-(3-chloro-2-pyrydinyl)-3-trifluoromethyl-lH pyrazol-5-yl]-6-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (DMSO-ds,TMS) 5 (ppm): 2.41 (3H, s), 7.77 (1H, dd, J=8Hz, 4Hz), 7.87 (1H, s), 7.93 (1H, s), 7.98 (1H, s), 8.36 (1H, d, J=8Hz), 8.63 (1H, d, J=4Hz). 20 Reference Preparation Example 32-(2) According to the same manner as that of Reference Preparation Example 1, 8-bromo-2-[l-(3-chloro-2-pyridinyl)-3 500 -trifluoromethyl-1H-pyrazol-5-yl]-6-methyl-4H-3,1 benzoxazine-4-one was used in place of 6-chloro-2- [1- (3-chloro -2-pyridinyl) -3-trifluoromethyl-lH-pyrazol-5-yl] -8-methyl-4 H-3,1-benzoxazine-4-one to obtain N-[6-bromo-2 5 (hydrazinocarbonyl)-4-methylphenyl]-1-(3-chloro-2-pyridinyl )-3-trifluoromethyl-1H-pyrazole-5-carboxamide of the formula:

F

3 C 0 Br CH 3 N,7 NY N H CYrO N'NH2 N H N-[6-bromo-2-(hydrazinocarbonyl)4-methylphenyl)-1-(3 10 chloro-2-pyridinyl)-3-trifluoromethyl-lH-pyrazole-5 carboxamide 1 H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 2.31 (3H, s), 4.33 (2H, brs), 7.24 (1H, s), 7.43 (1H, s), 7.57-7.65 (2H, m), 8.15 (1H, d, J=8Hz), 8.49 (1H, d, J=4Hz), 9.38 (1H, brs), 10.31 (1H, brs). 15 Reference Preparation Example 33-(1) According to the same manner as that of Reference Preparation Example 31-(1), 2-amino-6-chlorobenzoic acid was used in place of 2-amino-3,5-dimethylbenzoic acid to obtain 5-chloro-2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H 20 pyrazol-5-yl)-4H-3,1-benzoxazine-4-one of the formula: 501

F

3 C C1 N N CI N 5-Chloro-2- [1- (3-chloro-2-pyridinyl) -3-trifluoromethyl-1H pyrazole-5-yl)-4H-3,1-benzoxazine-4-one H-NMR (DMSO-d, , TMS) 6 (ppm): 6. 91 (1H, d, J=8Hz) , 7.68 (1H, 5 d, J=8Hz), 7.77 (18, t, J=8Hz), 7.83 (1H, dd, J=8Hz, 4Hz), 7.91 (1H, s), 8.37 (1H, d, J=8Hz), 8.64 (1H, d, J=4Hz). Reference Preparation Example 33-(2) ,According to the same manner as that of Reference Preparation Example 1, 5-chloro-2- [1- (3-chloro-2-pyridinyl) 10 3-trifluoromethyl-1H-pyrazol-5-yl)-4H- 3 , 1-benzoxazine-4-one was used in place of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-lH-pyrazol-5-yl]-8-methyl-4H- 3 ,1 benzoxazine-4-one to obtain N-[3-chloro-2 (hydrazinocarbonyl) phenyl] -1- (3-chloro-2-pyridinyl) -3 15 trifluoromethyl-lH-pyrazole-5-carboxamide of the formula:

F

3 C 0 NY HC NN 0 NH2 N- (3-chloro-2- (hydrazinocarbonyl)phenyl] -1- (3-chloro-2 pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carboxamide H-NMR (DMSO-d, , TMS) 5 (ppm) : 4. 47 (2H, brs) , 7. 32-7. 50 (3H, -502 m), 7.65-7.75 (2H, m), 8.25 (lH, d, J=8Hz), 8.56 (1H, d, J=4Hz), 9.58 (1H, brs), 10.29 (1H, brs). Reference Preparation Example 34-(1) According to the same manner as that of Reference 5 Preparation Example 31-(1), 2-amino-5-chlorobenzoic acid was used in place of 2-amino-3,5-dimethylbenzoic acid to obtain 6-chloro-2- [1- (3-chloro-2-pyridinyl) -3-trifluoromethyl-lH pyrazol-5-yl]-4H-3,1-benzoxazine-4-one of the formula:

F

3 C

N

1 CI N 10 6-Chloro-2-(1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H pyrazol-5-yl)-4H-3,1-benzoxazine-4-one 'H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 7.02 (1H, d, J=8Hz), 7.83 (lH, dd, J=8Hz, 4Hz), 7.87-7.92 (2H, m), 8.08 (1H, s), 8.37 (1H, d, J=8Hz), 8.64 (1H, d, J=4Hz).' 15 Reference Preparation Example 34-(2) According to the same manner as that of Reference Preparation Example 1, 6-chloro-2- [1- (3-chloro-2-pyridinyl) 3-trifluoromethyl-lH-pyrazol-5-yl)-4H-3,1-benzoxazine-4-one was used in place of 6-chloro-2-[l-(3-chloro-2-pyridinyl)-3 20 trifluoromethyl-1H-pyrazol-5-yl]-8-methyl-4H-3,1 benzoxazine-4-one to obtain N-[4-chloro-2 (hydrazinocarbonyl)phenyl)-1-(3-chloro-2-pyridinyl)-3- 503 trifluoromethyl-1H-pyrazole-5-carboxamide of the formula:

F

3 C 0 Cl N, N

.,NH

2 Ci ,O N "N H N- (4-chloro-2- (hydrazinocarbonyl) phenyl] -1- (3-chloro-2 pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carboxamide 5 'H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 7.52-7.56 (2H, m), 7.73 (1H, dd, J=8Hz, 4Hz), 7.85 (1H, s), 8.19 (1H, d, J=8Hz), 8.29 (1H, d, J=8Hz), 8.58 (1H, d, J=4Hz), 10.30 (1H, brs), 12.52 (1H, brs). Reference Preparation Example 35-(1) According to the same manner as that of Reference 10 Preparation Example 31-(1), 2-amino-3,5-dibromobenzoic acid was used in'place of 2-amino-3, 5-dimethylbenzoic acid to obtain 2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazol-5 yl]-6,8-dibromo-4H-3,1-benzoxazine-4-one of the formula:

F

3 C N 0 0 N CI N N Br Br. 15 2-[1-(3-Chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazol-5 yl]-6,8-dibromo-4H-3,1-benzoxazine-4-one H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 7.77 (1H, dd, J=8Hz, 4Hz), 7.94 (1H, s), 8.19-8.21 (1H, m), 8.35-8.39 (2H, m), 8.63 (1H, d, J=4Hz).

-504 Reference Preparation Example 35-(2) According to the same manner as that of Reference Preparation Example 1, 2-[1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-1H-pyrazol-5-yl]-6,8-dibromo-4H-3,1 5 benzoxazine-4-one was used in place of 6-chloro-2-[1-(3-chloro -2-pyridinyl)-3-trifluoromethyl-1H-pyrazol-5-yl]-8-methyl-4 H-3,1-benzoxazine-4-one to obtain N-[4,6-dibromo-2 (hydrazinocarbonyl)phenyll-1-(3-chloro-2-pyridinyl)- 3 trifluoromethyl-1H-pyrazole-5-carboxamide of the formula:

F

3 C 0 Br . Br NJ1% N ' N H0 ,H2 CN H 10 N-[4,6-dibromo-2-(hydrazinocarbonyl)phenyll-1-(3-chloro-2 pyridinyl) -3-trifluoromethyl-lH-pyrazole-5-carboxamide IH-NMR (DMSO-d 6 , TMS) 6 (ppm) : 4.40 (2H, brs), 7.61 (1H, s), 7.66 (1H, dd, J=8Hz, 4Hz), 7.79 (1H, s), 8.08 (1H, s), 8.21 (1H, d, 15 J=8Hz), 8.54 (1H, d, J=4Hz), 9.60 (1H, brs), 10.62 (1H, brs). Reference Preparation Example 36-(1) According to the same manner as that of Reference Preparation Example 31-(1), 2-amino-3,5-diiodobenzoic acid was used in place of 2-amino-3, 5-dimethylbenzoic acid to obtain 20 2-[l-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazol-5 yl]-6,8-diiodo-4H-3,1-benzoxazine-4-one of the formula: 505

F

3 C N, 0 0 N C1 N . 2-[1-(3-Chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazol-5 yl]-6,8-diiodo-4H-3,1-benzoxazine-4-one H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 7.74 (1H, dd, J=8Hz, 4Hz), 7.89 5 (1H, s), 8.31-8.35 (2H, m), 8.59-8.63 (2H, m). Reference Preparation Example 36-(2) According to the same manner as that of Reference Preparation Example 1, 2-[1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-1H-pyrazol-5-yl]-6,8-diiodo-4H-3,1 10 benzoxazine-4-one was used in place of 6-chloro-2-[1-(3 chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazol-5-yl]-8 methyl-4H-3,1-benzoxazine-4-one to obtain N-[4, 6-diiodo-2 (hydrazinocarbonyl)phenyl]-1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-1H-pyrazole-5-carboxamide of the formula:

F

3 C 0 N H , NH2 N H 15 N-[4, 6-diiodo-2- (hydrazinocarbonyl) phenyl] -1- (3-chloro-2 pyridinyl)-3-trifluoromethyl-lH-pyrazole-5-carboxamide 1 H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 4.39 (2H, brs), 7.66 (1H, dd, J=8Hz, 4Hz), 7.71 (1H, s), 7.79 (1H, s), 8.20 (1H, d, J=8Hz), ,506 8.33 (1H, s), 8.53 (1H, d, J=4Hz), 9.51 (1H, brs), 10.58 (1H, brs). Reference Preparation Example 37-(1) According to the same manner as that of Reference 5 Preparation Example 31-(1), 2-amino-4-chlorobenzoic acid was used in place of 2-amino-3,5-dimethylbenzoic acid to obtain 7-chloro-2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-lH pyrazol-5-yl)-4H-3,l-benzoxazine-4-one of the formula:

F

3 C

N

1 N CI 10 7-Chloro-2-[I-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H pyrazol-5-yl]-4H-3,1-benzoxazine-4-one 1H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 7.02 (1H, s), 7.68 (1H, d, J=8Hz), 7.84 (1H, dd, J=8Hz, 4Hz), 7.91 (lH, s), 8.10 (1H, d, J=8Hz), 8.38 (1H, d, J=8Hz), 8.64 (1H, d, J=4Hz). 15 Reference Preparation Example 37-(2) According to the same manner as that of Reference Preparation Example 1, 7-chloro-2-[1- (3-chloro-2-pyridinyl) 3-trifluoromethyl-1H-pyrazol-5-yl]-4H-3,1-benzoxazine-4-one was used in place of 6-chloro-2-[l-(3-chloro-2-pyridinyl) 20 3-trifluoromethyl-lH-pyrazol-5-yl]-8-methyl-4H-3,1 benzoxazine-4-one to obtain N-[5-chloro-2- ,507 (hydrazinocarbonyl)phenyl)-1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-1H-pyrazole-5-carboxamide of the formula: CI

F

3 C N N H H NNH Ci O N N H N-[5-chloro-2-(hydrazinocarbonyl)phenyl]-1-(3-chloro-2 5 pyridinyl) -3-trifluoromethyl-lH-pyrazole-5-carboxamide 1 H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 7.31 (1H, d, J=8Hz), 7.55 (1H, s), 7,.75 (1H, dd, J=8Hz, 4Hz), 7.82 (1H, d, J=8Hz), 8.27 (lH, s), 8.31 (1H, d, J=8Hz), 8.59 ,(1H, d, J=4Hz), 10.32 (1H, brs), 12.86 (1H, brs). 10 Reference Preparation Example 38-(1) According to the same manner as that of Reference Preparation Example 31-(l), 2-amino-5-methylbenzoic acid was used in place of 2-amino-3,5-dimethylbenzoic acid to obtain 2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazol-5 15 yl]-6-methyl-4H-3,1-benzoxazine-4-one of the formula:

F

3 C N., 00 ClN / N

CH

3 . 2-[l-(3-Chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazole-5 -yl]-6-methyl-4H-3,1-benzoxazine-4-one 508 'H-NMR (DMSO-d 6 ,TMS) & (ppm): 2.43 (3H, s), 6.94 (iH, d, J=8Hz), 7.69 (1H, d, J=8Hz), 7.80-7.85 (2H, m), 7.92 (1H, s), 8.36 (1H, d, J=8Hz), 8.63 (1H, d, J=4Hz). Reference Preparation Example 38-(2) 5 According to the same manner as that of Reference Preparation Example 1, 2-[1-(3-chloro-2-pyridinyl)- 3 trifluoromethyl-1H-pyrazol-5-yl) -6-methyl-4H-3, 1 benzoxazine-4-one was used in place of 6-chloro-2- [1- (3-chloro -2-pyridinyl)-3-trifluoromethyl-lH-pyrazol-5-yl]-8-methyl-4 10 H-3,1-benzoxazine-4-one to obtain N-[2-(hydrazinocarbonyl) 4-met.hylphenyll -1- (3-chloro-2-pyridinyl) -3-trifluoromethyl 1H-pyrazole-5-carboxamide of the formula:

F

3 C N CH 3 N H i .,NH2 Cl0 N N N H N-[2-(hydrazinocarbonyl)-4-methylphenyl]-1-(3-chloro-2 15 pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carboxamide H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 2.29 (3H, s), 4.71 (2H, brs), 7.29 (1H, d, J=8Hz), 7.51-7.54 (1H, m), 7.61-7.63 (1H, m), 7.72-7.74 (1H, m), 8.07 (lH, d, J=8Hz), 8.29 (1H, d, J=8Hz), 8.56-8.59 (1H, m), 10.13 (1H, brs), 12.52 (1H, brs). 20 Reference Preparation Example 39-(1) According to the same manner as that of Reference Preparation Example 31-(1), 2-amino-6-methylbenzoic acid was 509 used in place of 2-amino-3,5-dimethylbenzoic acid to obtain 2-[l-(3-chloro-2-pyridinyl)-3-trifluoromethyl-lH-pyrazol-5 yl]-5-methyl-4H-3,1-benzoxazine-4-one of the formula:

F

3 C NCN 0 0CH N t- CH 3 1 3 5 2-[1-(3-Chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazole-5 -yl)-5-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 2.68 (3H, s), 6.82 (1H, d, J=8Hz), 7.44 ,(lH, d, J=8Hz), 7.70 (1H, t, J=8Hz), 7.82 (lH, dd, J=8Hz, 4Hz), 7.85 (i, s), 8.36 (1H, d, J=8Hz), 8.64 (1H, d, J=4Hz). 10 Reference Preparation Example 39-(2) According to the same manner as that of Reference Preparation Example 1, 2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 1H-pyrazol-5-yl]-5-methyl-4H-3,l-benzoxazine-4-one was used in place of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3 15 trifluoromethyl-lH-pyrazol-5-yl]-8-methyl-4H-3,1 benzoxazine-4-one to obtain N-[2-(hydrazinocarbonyl)- 3 methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-lH -pyrazole-5-carboxamide of the formula:

F

3 C 0 N, N CH 3 N H Ci N 0

NH

510 N- [2- (hydrazinocarbonyl) -3-methylphenyl] -1- (3-chloro-2 pyridinyl) -3-trifluoromethyl-1H-pyrazole-5-carboxamide H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 2.27 (3H, s), 4.48 (2H, brs), 7.11 (1H, d, J=8Hz), 7.24-7.35 (2H, m), 7.65-7.72 (2H, m), 8.25 (1H, 5 d, J=8Hz), 8.55 (1H, d, 'J=4Hz), 9.35 (1H, brs), 10.15 (1H, brs) . Reference Preparation Example 40-(1) According to the same manner as that of Reference Preparation Example 31-(1), 2-amino-3,5-dichlorobenzoic acid was used in place of 2-amino-3,5-dimethylbenozoic acid to 10 obtain 2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H pyrazol-5-yl)-6,8-dichloro-4H-3,1-benzooxazine-4-one of the formula:

F

3 C N 0 0 NI CI CI. 2-[1- (3-Chloro-2-pyridinyl) -3-trifluoromethyl-1H-pyrazole 15 5-yl]-6,8-dichloro-4H-3, 1-benzooxazine-4-one 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 7.78 (1H, dd, J=8Hz, 4Hz), 7.95 (1H, s), 8.06 (1H, s), 8.14 (1H, s), 8.37 (1H, d, J=8Hz), 8.63 (1H, d, J=4Hz). Reference Preparation Example 40-(2) 20 According to the same manner as that of Reference Preparation Example 1, 2-[l-(3-chloro-2-pyridinyl)-3 trifluoromethyl-1H-pyrazol-5-yl) -6, 8-dichloro-4H-3, 1-benzox -511 azine-4-one was used in place of 6-chloro-2-[1-(3-chloro 2-pyridinyl) -3-trifluoromethyl-lH-pyrazol-5-yl] -8-methyl-4H -3,1-benzoxazine-4-one to obtain N-[4, 6-dichloro-2 (hydrazinocarbonyl)phenyl] -1- (3-chloro-2-pyridinyl) -3 5 trifluoromethyl-1H-pyrazole-5-carboxamide of the formula: C1 C1

F

3 C O C NI 0 N H ,NH2 CI"1N H N- [ 4, 6-dichloro-2- (hydrazinocarbonyl) phenyl] -1- (3-chloro-2 -pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carboxamide 1 H-NMR (DMSO-d 6 , TMS) 6 (ppm) : 4. 38 (2H, brs) , 7. 47 (1H, s) , 7. 66 10 (lH, dd, J=8Hz, 4Hz), 7.79 (18, s), 7.86 (1H, s), 8.21 (1H, d, J=8Hz), 8.53 (1H, d, J=4Hz), 9.64 (1H, brs), 10.63 (1H, brs). Reference Preparation Example 41-(1) To a mixture of 1.7g of 2-amino-5-chlorobenzoic acid and 100 ml of N,N-dimethylformamide was added 1.8g of 15 N-bromosuccinimide at room temperature, and the mixture was stirred at room temperature for 10 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 1.lg of 2-amino-3-bromo-5 chlorobenzoic acid of the formula: HO 0

H

2 N 20 Br C1.

512 2-Amino-3-bromo-5-chlorobenzoic acid 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 6.87 (2H, brs), 7.74 (1H, d, J=2Hz), 7.76 (1H, d, J=2Hz). Reference Preparation Example 41-(2) 5 According to the same manner as that of Reference Preparation Example 31- (1), 2-amino-3-bromo-5-chlorobenzoic acid was used in place of 2-amino-3,5-dimethylbenzoic acid to obtain 8-bromo-6-chloro-2-[1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-lH-pyrazol-5-yl]-4H-3,1-benzoxazine-4-one 10 of the formula:

F

3 C N 0 0 N CIt ~N Br CI. 8-Bromo-6-chloro-2-[1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-1H-pyrazol-5-yl]-4H-3,1-benzoxazine-4-one 1 H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 7.77 (lH, dd, J=8,5Hz), 7.94 (lH, 15 s), 8.10 (lH, d, J=2Hz), 8.27 (1H, d, J=2Hz), 8.37 (1H, d, J=8Hz), 8.63 (1H, d, J=4Hz). Reference Preparation Example 41-(3) According to the same manner as that of Reference Preparation Example 1, 8-bromo-6-chloro-2-[1- (3-chloro-2 20 pyridinyl) -3-trifluoromethyl-1H-pyrazol-5-yl] -4H-3, 1 benzoxazine-4-one was used in place of 6-chloro-2- [1- (3-chloro -2-pyridinyl) -3-trifluoromethyl-1H-pyrazol-5-yl] -8-methyl-4 -513 H-3,1-benzoxazine-4-one to obtain N-(6-bromo-4-chloro- 2 (hydrazinocarbonyl) phenyl) -1- (3-chloro-2-pyridinyl) -3 trifluoromethyl-1H-pyrazole-5-carboxamide of the formula:

F

3 C Br CI Fci 0 H Kr N, N C', N H . 1'NH2 N H 5 N-[6-bromo-4-chloro-2-(hydrazinocarbonyl)phenyl]-1-(3 chloro-2-pyridinyl)-3-trifluoromethyl-H-pyrazole-5 carboxamide 1 H-NMR (DMSO-d 6 , TMS) 5 (ppm): 4.35 (2H, brs), 7.50 (1H, s), 7.66 (1H, dd, J=8Hz, 4Hz), 7.79 (1H, s), 7.98 (1H, s), 8.21 (1H, d, 10 J=8Hz), 8.53 (lH, d, J=4Hz), 9.60 (1H, brs), 10.63 (lH, brs). Reference Preparation Example 42-(1) According to the same manner as that of Reference Preparation Example 31- (1) , 2-amino-4-methylbenozic acid was used in place of 2-amino-3,5-dimethylbenzoic acid to obtain 15 2-[l-(3-chloro-2-pyridinyl)-3-trifluoromethyl-lH-pyrazol-5 yl]-7-methyl-4H-3,1-benzoxazine-4-one of the formula:

F

3 C N) 0 0 N C N

CH

3 . 2-[1-(3-Chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazole-5 514 -yl]-7-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 2.41 (3H, s), 6.84 (1H, s), 7.46 (1H, d, J=8Hz), 7.82-7.85 (2H, m), 8.00 (1H, d, J=8Hz), 8.37 (1H, d, J=8Hz), 8.64 (1H, d, J=4Hz). 5 Reference Preparation Example 42-(2) According to the same manner as that of Reference Preparation Example 1, 2-[1-(3-chloro-2-pyridinyl)-3 trifluoromethyl-1H-pyrazol-5-yl]-7-methyl-4H-3,1 benzoxazine-4-one was used in place of 6-chloro-2- [1- (3-chloro 10 -2-pyridinyl) -3-trifluoromethyl-H-pyrazol-5-yll -8-methyl-4 H-3,1,-benzoxazine-4-one to obtain N-[2- (hydrazinocarbonyl) 5-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 1H-pyrazole-5-carboxiamide of the formula:

CH

3

F

3 C N N H ,NH2 N H 15 Reference Preparation Example 43-(1) A mixture of 1.85g of 2-amino-5-chloro-3-methylbenzoic acid, 0.90g of triphosgene and 10 ml of tetrahydrofuran was stirred at room temperature for 5 hours. The reaction mixture was concentrated under reduced pressure, and a precipitated 20 crystal was washed with water to obtain 1.20 g of 6-chloro-8-methyl-1H-benzo[d)-1,3-oxazine-2,4-dione of the 515 formula:

H

3 C CI HN 0 0 6-Chloro-8-methyl-1H-benzo[d] -1, 3-.oxazine-2, 4-dione H-NMR (DMSO-d,TMS) 6 (ppm): 2.33 (3H, s), 7.69 (lH, d, J=2Hz), 5 7.73 (1H, d, J=2Hz), 11.18 (1H, s). Reference Preparation Example 43-(2) A mixture of 1.05 g of 6-chloro-8-methyl-1H-benzo [d]-1, 3 oxazine-2,4-dione, 0.46 g of methyl carbazate and 20 ml of methanol was heated to reflux for 3 hours. After the reaction 10 mixture was allowed to cool to around room temperature, water was poured thereto and the mixture was extracted with ethyl acetate three times. The resulting organic layer was concentrated under reduced pressure, and the residue was washed with toluene to obtain 0.77 g of N-(2-amino-5-chloro-3 15 methylbenzoyl)-N'-methoxycarbonylhydrazine of the formula:

H

3 C C1

H

2 N H ,N OCH3 O N ' H . 0 N- (2-amino-5-chloro-3-methylbenzoyl) -N' ethoxycarbonylhydrazine 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 2.10 (3H, s), 3.63 (3H, s), 6.32 20 (2H, brs), 7.19 (lH, d, J=2Hz), 7.45 (1H, d, J=2Hz), 9.14 (lH, 516. brs), 10.12 (lH, brs). Reference Preparation Example. 44- (1) To a mixture of 1.9 g of 3-amino-2-naphthoic acid and 100 ml of N,N-dimethylformamide was added 1.3 g of 5 N-chlorosuccinimde at room temperature, and the mixture was stirred at room temperature-for 10 hours. After water was added to the reaction mixture, a deposited precipitate was collected by filtration to obtain 1.3 g of 3-amino-4-chloro-2-naphthoic acid of the formula: HO 0

H

2 N CI 10 3-Amino-4-chloro-2-naphthoic acid H-NMR (DMSO-dr,TMS) 6 (ppm): 7.27-7.31 -(1H, m), 7.60-7.64 (1H, m), 7.88 (1H, d, J=8Hz), 7.93 (1H, d, J=8Hz), 8.53 (1H, s). Reference Preparation Example 44-(2) 15 According to the same manner as that of Reference Preparation Example 31-(1) , 3-amino-4-chloro-2-naphthoic acid was used in place of 2-amino-3, 5-dimethylbenzoic acid to obtain 10-chloro-2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H pyrazol-5-yl)-4H-naphtho(2,3-d][1,3]oxazine-4-one of the 20 formula: 517

F

3 C N, 0 0 N N CI 10-Chloro-2-[1-(3-chloro-2--pyridinyl)-3-trifluoromethyl-1H pyrazole-5-yl]-.4H-naphtho[2,3-d] [1, 3]oxazine-4-one H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 7.77 (1H, t, J=7Hz), 7.84 (lH, 5 dd, J=8Hz, 4Hz), 7.87-7.94 (2H, m), 8.24 (1H, d, J=8Hz), 8.35 (1H, d, J=8Hz), 8.42 (1H, d, J=8Hz), 8.67 (1H, d, J=4Hz), 8.91 (1H, s). Reference Preparation Example 44-(3) According to the same manner as that of Reference 10 Preparation Example 1, 10-chloro-2-[1-(3-chloro-2-pyridinyl) -3-trifluoromethyl-lH-pyrazol-5-yl]-4H-naphtho[2,3-d] [1,3] oxazine-4-one was used in place of 6-chloro-2-[1-(3-chloro 2-pyridinyl) -3-triffluoromethyl-1H-pyrazol-5-yl],8-methyl-4H -3,1-benzoxazine-4-one to obtain N-[1-dhloro-3 15 (hydrazinocarbonyl)-2-nsphthyl]-l-(3-chloro-2-pyridinyl)-3 trifluoromethyl-1H-pyrazole-5-carboxiamide of the formula:

F

3 C OCI N N ' N H 518 N-[1-chloro-3-(hydrazinocarbonyl)-2-naphthyl]-1-(3-chloro 2-pyridinyl) -3-trifluoromethyl-1H-pyra zole-5-carboxiamide 'H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 4.39 (2H, brs), 7.65 (1H, dd, J=8Hz, 4Hz), 7.70 (lH, t, J=8Hz), 7.78 (1H, t, J=8Hz), 7.86 (lH,' 5 s), 8.05-8.11 (2H, m), 8.18-8.24 (2H, m), 8.53 (1H, d, J=4Hz), -9.70 (1H, brs-), 10.77 (lH, brs). Reference Preparation Example 45-(l) According .to the same manner as that of Reference Preparation Example 44-(l), N-bromosuccinimide was used in 10 place of N-chlorosuccinimide to obtain 3-amino-4-bromo 2-naphthoic acid of the formula: HO 0

H

2 N Br 3-Amino-4-bromo-2-naphthoic acid H-NMR (DMSO-d 6 ,TMS) 5 (ppm) : 7.28 (1H, t, J=8Hz), 7.61 (lH, 15 t, J=BHz), 7.86 (1H, d, J=8Hz), 7.92 (1H, d, J=8Hz), 8.57 (1H, s). Reference Preparation Example 45-(2) According to the same manner as that of Reference Preparation Example 31-(1), 3-amino-4-bromo-2-naphthoic acid 20 was used in place of 2-amino-3, 5-dimethylbenzoic acid to obtain 10-bromo-2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H pyrazol-5-yl]-4H-naphtho[2,3-d] [1,3]oxazine-4-one of the 519 formula:

F

3 C N Br 10-Bromo-2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H pyrazol-5-yl)-4.H-naphtho[2,3-d] [1, 3)oxazine-4-one 5 1H-NMR (DMSO-d 6 ,TMS) .5 (ppm): 7.76 (1H, t, J=8Hz), 7.82 (1H, dd, J=8Hz, 4Hz), 7.87-7.94 (2H, m), 8.24 (1H, d, J=8Hz), 8.34 (1H, d, J=8Hz), 8.42 (1H, d, J=8Hz), 8.67 (lH, d, J=4Hz), 8.95 (lH, s) Reference Preparation Example 45-(3) 10 According to the same manner as that of Reference Preparation Example 1, 10-bromo-2-(1-(3-chloro-2-pyridinyl) 3-trif-luoromethyl-1H-pyrazol-5-yl)-4H-naphtho[2,3-d] [1,3] oxazine-4-one was used in place of 6-chloro-2-[1.-(3-chloro 2-pyridinyl)-3-trifluoromethyl-1H-pyrazol-5-yl]-8-methyl-4H 15 -3,1-benzoxazine-4-one to obtain N-[1-bromo-3 (hydrazinocarbonyl) -2-naphthyl) -1- (3-chloro-2-pyridinyl) -3 trifluoromethyl-1H-pyrazole-5-carboxiamide of the formula: . 520

F

3 CN Br CI 0 N NH2 CIt'N - H N-[l-bromo-3-(hydrazinolcarbonyl)-2-naphthyl]-1-(3-chloro-2 -pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carboxiamide 'H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 4.37 (2H, brs), 7.64 (1H, dd, 5 J=8Hz, 4Hz), 7.70 (lH, d, J=8Hz), 7.77 (1H, t, J=BHz), 7.87 (lH, s), 8.05-8.10 (2H, m), 8.17-8.24 (2H, m), 8.53 (1H, d, J=4Hz), 9.66 (1H, brs), 10.80 (I, brs). Reference Preparation Example 46-(1) A mixture of 1.0g of 3-bromo-l-(3-chloro-2-pyridinyl) 10 1H-pyrazole-5-carboxylic acid and 2 ml of thionyl chloride was heated to reflux for 2 hours. The reaction mixture was allowed to cool to room temperature, and concentrated under reduced pressure. The resulting residue was dissolved in 15 ml of acetonitrile, and 0.88g of 2-amino-3, 5-dibromobenzoic acid was 15 added. The mixture was stirred at room temperature for 30 minutes. To the mixture, 0.7 ml of triethylamine was added. After the mixture was stirred at room temperature for 30 minutes, 1.4 ml of triethylamine was further added. After the mixture was stirred at room temperature for 30 minutes, 0.5 ml of 20 methanesulfonyl chloride was added, and the mixture was stirred at room temperature for 5 hours. Water was poured into the 521 reaction mixture, and the mixture was concentrated under reduced pressure. The resulting residue was washed with water and methyl tert-butyl ether to obtain 0.80 g of 2-[3-bromo 1-(3-chloro-2-pyridinyl)-lH-pyrazol-5-yl]-6,8-dibromo-4H-3, 5 1-benzoxazine-4-one of' the formula: Br 0 0 N O O ClN CI N Br Br. 2-[3-5romo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6,8 dibromo-4H-3,1-benzoxazine-4-one H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 7.56 (1H, s), 7.71 (1H, dd, J=8Hz, 10 4Hz), 8.18 (1H, d, J=2Hz)., 8.32 (l H, d, J=8 H z), 8.35 (lH, d, J=2Hz), 8.59 (1H, d, J=4Hz). Reference Preparation Example 47-(1) According to the same manner as that of Reference Preparation Example 14, 2-chloropyridine was used in place of 15 2,3-dichloropyridine to obtain 2-(3-trifluoromethyl-1H pyrazol-1-yl)pyridine of the formula:

F

3 C N "N 2-(3-Trifluoromethyl-lH-pyrazol-1-yl)pyridine 1 H-NMR (CDCl 3 ,TMS) 5 (ppm): 6.71 (1H, d, J=2Hz), 7.27-7.28 (1k, 522 m), 7.86 (1H, t, J=8Hz), 8.04 (1H, d, J=8Hz), 8.44 (1H, d, J=4Hz), 8.63 (lH, d, J=2Hz). Reference Preparation Example 47-(2) According to the same manner as that of Reference 5 Preparation Example 15, 2-(3-trifluoromethyl-1H-pyrazol-l yl)pyridine was used in place of 3-chloro-2-(3 trifluoromethyl-1H-pyrazol-1-yl)pyridine to obtain 1-(2-pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carboxylic acid of the formula:

F

3 C N N C0 2 H 10 1- (2-Pyridinyl) -3-trifluoromethyl-lH-pyrazole-5-carboxylic acid H-NMR (DMSO-dr>) 6 (ppm): 7.47 (1H, s), 7.59 (1H, dd, J=8Hz, 5Hz), 7.78 (1H, d, J=8Hz), 8.09 (1H, t, J=8Hz), 8.55 (1H, d, 15 J=5Hz). Reference Preparation Example 47-(3) According to the same manner as that of Reference Preparation Example 13, 1- (2-pyridinyl) -3-trifluoromethyl 1H-pyrazole-5-carboxylic acid was used in place of 20 1-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid to obtain 6-chloro-2-[1-(2-pyridinyl)-3-trifluoromethyl-1H pyrazol-5-yl)-8-methyl-4H-3,1-benzoxazine-4-one of the - 523 formula:

F

3 C / N / . ' N..

H

3 C 6-Chloro-2-(1-(2-pyridinyl)-3-trifluoromethyl-1H-pyrazol- 5 yl3-8-methyl-4H-3,1-benzoxazine-4-one 5 1 H-NMR (CDCl 3 ,TMS) 5 (ppm): 2.15 (3H, s), 7.26 (1H, s), 7.42 (1H, dd, J=8Hz, 4Hz), 7.58 (1H, s), 7.79 (lH, d, J=8Hz), 7.96-8.00 (2H, m), 8.43 (1H, d, J=4Hz). Reference Preparation Example 47-(4) According to the same manner as that of Reference 10 Preparation Example 1, 6-chloro-2-[l-(2-pyridinyl)-3 trifluoromethyl-lH-pyrazol-5-yl)-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 6-chloro-2-[1-(3 chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazol-5-yl]-8 methyl-4H-3,1-benzoxazine-4-one to obtain N-[4-chloro-2 15 (hydrazinocarbonyl)-6-methylphenyl)-l-(2-pyridinyl)-3 trifluoromethyl-1H-pyrazole-5-carboxamide of the formula:

F

3 C

H

3 C CI bON N H N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl)-1-(2 pyridinyl)-3-trifluoromethyl-1H-pyrazole-5-carboxamide - 524 'H-NMR (DMSO-d 6 ,TMS) 5 (ppm): 2.31 (3H, s), 4.44 (2H, s), 7.34-7.35 (2H, m), 7.50-7.55 (2H, m), 7.81 (1H, d, J=8Hz), 8.07 (1H, t, J=8Hz), 8.48 (1H, d, J=4Hz), 9.55 (1H, brs), 10.39 (1H, brs). 5 Reference Preparation Example 48-(1) According to the same manner as that of Reference Preparation Example 46-(1), 2-amino-3-bromo-5-chlorobenzoic acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 8-bromo-2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H 10 pyrazol-5-yl]-6-chloro-4H-3,1-benzoxazine-4-one of the formula: Br N, N 0 0 C N N N Br CI. 8-Bromo-2-(3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl ]-6-chloro-4H-3,1-benzoxazine-4-one 15 'H-NMR (DMSO-dr,TMS) 6 (ppm): 7.56 (1H, s), 7.72 (1H, dd, J=8Hz, 4Hz), 8.08 (1H, d, J=2Hz), 8.25 (1H, d, J=2Hz), 8.32 (1H, dd, J=8Hz, 2Hz), 8.59 (1H, dd, J=4Hz, 2Hz). Reference Preparation Example 49-(1) According to the same manner as that of Reference 20 Preparation Example 46-(l), 2-amino-3-bromo-5-methylbenzoic acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 8-bromo-2-{3-bromo-1-(3-chloro-2-pyridinyl)-1H- 525 pyrazol-5-yl] -6-methyl-4H-3, 1-benzoxazine-4-one of the formula: Br N C1 N N I I Br

CH

3 . 8-Bromo-2-[3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5 5 yl]-6-methyl-4H-3,1-benzoxazine-4-one 1 H-NMR (DMSO-d 6 ,TMS) 6 (ppm) : 2.40 (3H, s), 7.50 (1H, s), 7.71 (1H, dd, J=8Hz, 4Hz), 7.91 (1H, s), 7.96 (1H, s), 8.31 (1H, d, J=8Hz), 8.59 (1H, d, J=4Hz). Reference Preparation Example 50 10 According to the same manner as that of Reference Preparation Example 46-(1), 2-amino-3-chlorobenzoic acid was used in place of 2-amino-3,5-dibromobenzoi c acid to obtain 2-[3-bromo-1-(3-chloro-2-pyridinyl)-lH-pyrazol-5-yl]-8 chloro-4H-3,1-benzoxazine-4-one of the formula: Br N 15 C. 2- [3-Bromo-l-(3-chloro-2-pyridinyl) -lH-pyrazole-5-yl]- 8 chloro-4H-3,1-benzoxazine-4-one 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 7.52-7.61 (2H, m), 7.73 (1H, dd, J=8Hz, 4Hz), 7.93 (1H, dd, J=8Hz, 2Hz), 8.04 (1H, dd, J=8Hz, 526 2Hz), 8.32 (1H, dd, J=8Hz, 2Hz), 8.60 (lH, dd, J=4Hz, 2Hz). Reference Preparation Example 51-(1) According to the same manner as that of Reference Preparation Example 24, phenylhydrazine was used in place of 5 2-chlorophenylhydrazin'e to obtain 5-(2-furyl)-l-phenyl-3 trifluoromethyl-1H-pyrazole of the formula:

F

3 C N%N 0 5- (2-Furyl) -l-phenyl-3-trifluoromethyl-lH-pyrazole H-NMR (CDCl 3 ,TMS) 6 (ppm): 5..96 (1H, d, J=4Hz), 6.33 (1H, dd, 10 J=4Hz, 2Hz), 6.90 (lH, s), 7.43-7.48 (6H, m). Reference Preparation Example 51-(2) According to the same manner as that of Reference Preparation Example 25, 5-(2-furyl)-1-phenyl-3 trifluoromethyl-lH-pyrazole was used in place of 5-(2-furyl) 15 1- (2-chlorophenyl)-3-trifluoromethyl-1H-pyrazole to, obtain 1-phenyl-3-trifluoromethyl-H-pyrazole-5-carboxylic acid of the formula:

F

3 C N CO 2 H 1-Phenyl-3-trifluoromethyl-H-pyrazole-5-carboxylic acid 527 ' 1 H-NMR (CDC1 3 ,TMS) 6 (ppm): 7.29 (1H, s), 7.46-7.51 (5H, m). Reference Preparation Example 51-(3) According to the same manner as that of Reference Preparation Example 13, 1-phenyl-3-trifluoromethyl-1H 5 pyrazole-5-carboxylic acid was used in place of 1-(3-chloro-2-pyridinyl)-lH-pyrazole-5- carboxylic acid to obtain 6-chloro-2- (1-phenyl-3- trifluoromethyl-1H-pyrazol-5 yl)-8-methyl-4H-3,1- benzoxazine-4-one of the formula:

F

3 C N% 0 0 6N.

H

3 C C. 10 6-Chloro-2-(1-phenyl-3-trifluoromethyl-1H-pyrazol-5-yl)-8 methyl-4H-3,1-benzoxazine-4-one 'H-NMR (CDCl 3 , TMS) & (ppm) : 1. 88 (3H, s) , 7. 47-7. 54 (7H, m) , 7.99 (1H, d, J=2Hz). Reference Preparation Example 51-(4) 15 According to the same manner as that of Reference Preparation Example 1, 6-chloro-2-(1-phenyl-3 trifluoromethyl-H-pyrazol-5-yl)-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 6-chloro-2-[1-(3 chloro-2-pyridinyl) -3-trifluoromethyl-H-pyrazol-5-yl -8 20 methyl-4H-3,1-benzoxazine-4-one to obtain N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl)-l-phenyl-3 trifluoromethyl-1H-pyrazole-5-carboxamide of the formula: 528

H

3 C

F

3 C CI N N .. , H O N' 6 H 6N HNH2 N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl] -1-phenyl 3-trifluoromethyl-1H-pyrazole-5-carboxamide 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 2.19 (3H, s), 4.41 (2H, brs), 7.32 5 (1H, d, J=2Hz),, 7.46-7.52 (5H, m), 7.56 (2H, d, J=7Hz), 9.61 (1H, brs), 10.29 (1H, brs). Reference Preparation Example 52-(1) ,To a mixture of 1. 5 g of 2-amino-5-chlorobenzoic acid and 100 ml of N,N-dimethylformamide was added 1.8 g of 10 N-bromosuccinimide at room temperature, and the mixture was stirred at room temperature for 10 hours. After 30 ml of water was poured into the reaction mixture, the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride 15 solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 1.2 g of 2-amino-5-bromo-3-methylbenzoic acid of the formula: HO 0

H

2 N ,

H

3 C Br. 2-Amino-5-bromo-3-methylbenzoic acid 20 1 H-NMR (DMSO-d 6 , TMS) 6 (ppm): 2.11 (3H, s), 7.33 (1H, d, J=2Hz), 529 7.68 (1H, d, J=2Hz). Reference Preparation Example 52-(2) According to the same manner as that of Reference Preparation, Example 31- (1), 2-amino-5-bromo-3-methylbenzoic' 5 acid was used in place of 2-amino-3, 5-dimethylbenzoic acid to obtain 6-bromo-2-[1-(3-chloro-2-pyridinyl)- 3 trifluoromethyl-1H-pyrazol-5-yl]-8-methyl-4H-3,1 benzoxazine-4-one of the formula: F3C N, 0 0 Cq N / N 3C L Br 10 6-Bromo-2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-1H pyrazol-5-yl]-8-methyl-4H-3, 1-benzoxazine-4-one 1 H-NMR (DMSO-ds,TMS) 6 (ppm): 1.73 3H, s), 7.81 (1H, dd, J=8Hz, 4Hz), 7.90 (1H, s), 7.93 (1H, s), 8.04 (1H, t, J=lHz), 8.39 (1H, d, J=8Hz), 8.66 (1H, d, J=4Hz). 15 Reference Preparation Example 53-(1) To a mixture of 2.6 g of 2-amino-3-methylbenzoic acid and 100 ml of N,N-dimethylformamide was added 2.3 g of N-iodosuccinimide at room temperature, and the mixture was stirred at room temperature for 10 hours. After water was 20 poured to the reaction mixture, a deposited precipitate was collected by filtration to obtain 1.7 g of 2-amino-5-iodo-3-methylbenzoic acid of the formula: 530 HO 0

H

2 N

H

3 C I. 2-Amino-5-iodo-3-methylbenzoic acid 1 H-NMR (DMSO-d 6 , TMS) 6 (ppm) : 2. 08 (3H, s) , 7.44 (1H, d, J=lHz) , 7.86 (1H, d, J=lHz) . 5 Reference Preparation Example 53-(2) According to the same manner as that of Reference Preparation Example 31-(1), 2-amino-5-iodo-3-methylbenzoic acid was used in place of 2-amino-3,5-dimethylbenzoic acid to obtain 2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl 10 1H-pyrazol-5-yl]-6-iodo-8-methyl-4H-3,1-benzoxazine-4-one of the formula:

F

3 C N 0 0 N C, N

H

3 C & . 2-[1-(3-Chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazol-5 yl]-6-iodo-8-methyl-4H-3,1-benzoxazine-4-one 15 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm) : 1.70 (3H, s), 7.81 (1H, dd, J=8Hz, 4Hz), 7.89 (1H, s), 8.07 (lH, s), 8.19 (1H, s), 8.39 (1H, d, J=8Hz), 8.66 (1H, d, J=4Hz). Reference Preparation Example 54-(1) A mixture of 1.41 g of ethyl 2-(2-chlorobenzoyl)-3-(N,N 20 dimethylamino) acrylate (a compound described in JP-A 7-101940) , 531 0.30 g of hydrazine monohydrate and 5 ml of acetic acid was stirred at room temperature for 10 hours. The reaction mixture was concentrated under reduced pressure. Water was poured into the residue, and the mixture was extracted with ethyl acetate.' 5 The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain ethyl 3- (2-chlorophenyl) -1H-pyrazole-4-carboxylate of the formula: HN

OCH

2

CH

3 CI O 10 The resulting ethyl 3-(2-chlorophenyl)-lH-pyrazole- 4 carboxylate, 1.07 g of methyl iodide, 1.04 g of potassium carbonate and 5 ml of N,N-dimethylformaide were mixed under ice-cooling, and the mixture was stirred at room temperature for 10 hours. Water was poured into the reaction mixture, and 15 the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.72 g of ethyl 20 3- (2-chlorophenyl) -1-methyl-lH-pyrazole-4-carboxylate of the formula: .532

H

3 C, N' N,

OCH

2

CH

3 Cl - 0 and 0.48 g of ethyl 5- (2-chlorophenyl) -1-methyl-1H-pyrazole-4-carboxylate. Ethyl 3- (2-chlorophenyl) -1-methyl-1H-pyrazole-4-carboxylate 5 1 H-NMR (CDCl 3 ) 5 (ppm): 1.12 (3H, t, J=7Hz), 3.68 (3H, s), 4.09-4.15 (2H, m), 7.31 (1H, dd, J=7Hz, 2Hz), 7.38 (1H, td, J=7Hz, 1Hz), 7.44 (1H, td, J=8Hz, 2Hz), 7.52 (1H, dd, J=8Hz, 1Hz),,.8.01 (1H, s). Ethyl 5-(2-chlorophenyl)-l-me.thyl-lH-pyrazole-4-carboxylate 10 1 H-NMR (CDCl 3 ) 6 (ppm): 1.13 (3H, t, J=7Hz), 3.98 (3H, s), 4.14 (2H, q, J=7Hz), 7.27-7.35 (2H, m), 7.38-7.41 (1H, m), 7.43-7.45 (1H, m), 7.96 (1H, s). Reference Preparation Example 54-(2) Amixture of 0.72 g of ethyl 3-(2-chlorophenyl) -1-methyl 15 1H-pyrazole-4-carboxylate, 0.23 g of potassium hydroxide, 1 ml of water and 5 ml of ethanol was stirred at room temperature for 3 days. After the reaction mixture was concentrated under reduced pressure, water was poured into the resulting residue and the mixture was washed with methyl tert-butyl ether. The 20 aqueous layer was adjusted to around pH 3 by an addition of a 10% aqueous citric acid, and then extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous ,533 sodium sulfate, and concentrated under reduced pressure to obtain 0.61 g of 3-(2-chlorophenyl)-1-methyl-1H-pyrazole 4-carboxylic acid of the formula:

H

3 C, N N, OH C1 0 5 3-(2-Chlorophenyl)-l-methyl-1H-pyrazole-4-carboxylic acid 1 H-NMR (CDCl 3 ) 5 (ppm): 3.66 (3H, s), 7.30 (1H, dd, J=8Hz, 2Hz), 7.37 (1H, td, J=8Hz, 1Hz), 7.43 (1H, td, J=BHz, 2Hz), 7.51 (1H, dd, J=8Hz, 1Hz), 8.02 (1H, s). Reference Preparation Example 54-(3) 10 A mixture of 0.61 g of 3-(2-chlorophenyl)-1-methyl-lH pyrazole-4-carboxylic acid, 0.28 ml of thionyl chloride and 10 ml of toluene was heated to reflux for 1 hour. After the reaction mixture was allowed to cool to room temperature, it was concentrated under reduced pressure and the resulting 15 residue was dissolved in 10 ml of acetonitrile. Thereto 0.48 g of 2-amino-5-chloro-3-methylbenzoic acid was added, and the resulting mixture was stirred at room temperature for 30 minutes. To the mixture, 0.26 g of triethylamine was added, the mixture was stirred at room temperature for 30 minutes. 20 Thereto 0.52 g of triethylamine was further added, and the resulting mixture was stirred at room temperature for 30 minutes. Then, 0.30g of methanesulfonyl chloride was added to .534 % the reaction mixture under ice-cooling, and the mixture was stirred at room temperature for 10 hours. Water and ethyl acetate were poured into the reaction mixture, and 0.26 g of a solid was collected by filtration. In addition, the filtrate 5 was separated into two layers. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was washed with ethyl acetate to obtain 0.25 g of a solid. Both of these solids were 6-chloro-2-[3-(2-chlorophenyl)-1-methyl 10 lH-pyrazol-4-yl]-8-methyl-4H-3,1-benzoxazine-4-one of the formula:

H

3 C, N C1 N CCl

H

3 C 6-Chloro-2-[3-(2-chlorophenyl)-1-methyl-lH-pyrazol-4-yll-8 methyl-4H-3,1-benzoxazine-4-one 15 'H-NMR (DMSO-d 6 ) 5 (ppm): 1.86 (3H, s), 3.68 (3H, s), 7.52-7.63 (3H, m), 7.69-7.72 (2H, m), 7.81 (1H, d, J=2Hz), 8.18 (1H, s). Reference Preparation Example 54-(4) After 0.19 g of 6-chloro-2-(3-(2-chlorophenyl)-1-methyl 1H-pyrazol-4-yl]-8-methyl-4H- 3 ,1-benzoxazine-4-one, 0.10 g 20 of hydrazine monohydrate and 10 ml of N-methylpyrrolidinone were mixed under ice-cooling, the mixture was stirred at room ,535 temperature for 8 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure-to' 5 obtain 0.18 g of N-[4-chloro-2-(hydrazinocarbonyl)- 6 methylphenyl ] -3- (2-chlorophenyl) -1-methyl-1H-pyrazole- 4 carboxamide of the formula:

H

3 C

H

3 Cs O CI N N H

,NH

2 C1 O N H N-[4-chloro-2-(hydradinocarbonyl)-6-methylphenyl]-3-(2 10 chlorophenyl)-l-methyl-lH-pyrazole-4-carboxamide 'H-NMR (DMSO-d 6 ) 8 (ppm): 2.13 (3H, s), 3.60 (3H, s), 4.39 (2H, brs), 7.29 (lH, d, J=2Hz), 7.42-7.53 (4H, m), 7.60 (1H, d, J=8Hz), 8.11 (1H, s), 9.53 (2H, brs). Reference Preparation Example 55-(1) 15 According to the same manner as that of Reference Preparation Example 54- (2), ethyl 5- (2-chlorophenyl) -1 methyl-lH-pyrazole-4-carboxylate was used in place of ethyl 3-(2-chlorophenyl)-1-methyl-lH-pyrazole-4-carboxylate to obtain 5-(2-chlorophenyl)-1-methyl-H-pyrazole-4-carboxylic 20 acid of the formula: .536

,N

H

3 C.N / OH CI, O~ 5-(2-Chlorophenyl)-l-methyl-1H-pyrazole-4-carboxylic acid IH-NMR (CDCl 3 ) 5 (ppm): 3.97 (3H, s), 7.26-7.35 (2H, m), 7.37-7.39 (1H, m), 7.42-7.44 (1H, m), 7.98 (1H, s). 5 Reference Preparation Example 55-(2) According to the same manner as that of Reference. Preparation Example 54-(3), 5-(2-chlorophenyl)-1-methyl-1H pyrazole-4-carboxylic acid was used in place of 3- (2-chlorophenyl) -1-methyl-1H-pyrazole-4-carboxylic acid to 10 obtain 6-chloro-2-[5-(2-chlorophenyl)-1-methyl-1H-pyrazol 4-yl)-8-methyl-4H-3,1-benzoxazine-4-one of the formula:

N

3 NZ 0 0 H3C-O O Cl N/ I ci

H

3 C 6-Chloro-2-[5-(2-chlorophenyl)-1-methyl-lH-pyrazol-4-yl]-8 methyl-4H-3,1-benzoxazine-4-one 15 1 H-NMR (DMSO-d 6 ) 5 (ppm): 1.90 (3H, s), 3.99 (3H, s), 7.40-7.50 (3H, m), 7.56 (1H, d, J=8Hz), 7.71 (1H, d, J=2Hz), 7.82 (1H, d, J=2Hz), 8.63 (1H, s). Reference Preparation Example 55-(3) According to the same manner as that of Reference ,537 Preparation Example 54-(4), 6-chloro-2-[5-(2-chlorophenyl) 1-methyl-1H-pyrazol-4-yl]-8-methyl-4H-3,1-benzoxazine-4-one was used in place of 6-chloro-2-[3-(2-chlorophenyl)-1-methyl 1H-pyrazol-4-yl] -8-methyl-4H-3,1-benzoxazine-4-one to obtain' 5 N-(4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl]-5-(2 chlorophenyl)-1-methyl-1H-pyrazole-4-carboxamide of the formula:

H

3 C C1 0 /

N

H

3 C.N / N H H -.. NH2 C1 O N H N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl)-5-(2 10 chlorophenyl)-l-methyl-1H-pyrazole-4-carboxamide 'H-NMR (DMSO-d 6 ) 5 (ppm): 2.16 (3H, s), 3.94 (3H, s), 4.39 (2H, brs), 7.30 (1H, d, J=2Hz), 7.33-7.46 (5H, m), 8.36 (1H, s), 9.49-9.59 (2H, brm). Reference Preparation Example 56-(1) 15 To a mixture of 1.67 g of 2-amino-3-methoxybenzoic acid and 100 ml of N,N-dimethylformamide was added 1.3 g of N-chlorosuccinimide at room temperature, and the resulting mixture was stirred at room temperature for 10 hours. Water was poured into the reaction mixture, and a deposited 20 precipitate was collected by filtration to obtain 1.2 g of 2-amino-5-chloro-3-methoxybenzoic acid.

538 HO 0

H

2 N 1 ;

H

3 CO CI 2-Amino-5-chloro-3-methoxybenzoic acid 'H-NMR (DMSO-d,TMS) 5 (ppm): 3.84 (3H, s), 6.99 (1H, s), 7.28 (1H, s). 5 Reference Preparation Example 56-(2) According to the same manner as that of Reference Preparation Example 46-(l), 2-amino-5-chloro-3 methoxybenzoic acid was used in place of 2-amino-3,5 dibromobenzoic acid to obtain 2-(3-bromo-1-(3-chloro-2 10 pyridinyl) -1H-pyrazol-5-yl) -6-chloro-8-methoxy-4H-3, 1 benzoxazine-4-one of the formula: Br N y 0 N NIC

H

3 CO 2-[3-Bbromo-l-(3-chloro-2-pyridinyl) -1H-pyrazol-5-yl]- 6 chloro-8-methoxy-4H-3,1-benzoxazine-4-one 15 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 3.71 (3H, s), 7.45 (1H, d, J=2Hz), 7.48 (1H, s), 7.57 (1H, d, J=2Hz), 7.78 (1H, dd, J=8Hz, 4Hz), 8.28 (1H, dd, J=8Hz, 2Hz), 8.57 (1H, dd, J=4Hz, 2Hz). Reference Preparation Example 57-(1) To a mixture of 1.5 g of 2-amino-5-chlorobenzoic acid and 539 100 ml of N,N-dimethylformamide was added 2.7 g of N-iodosuccinimide at room temperature, and the mixture was stirred at room temperature for 24 hours. After 30 ml of water was poured into the reaction mixture, the mixture was extracted 5 with ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 1.2 g of 2-amino-5-chloro-3-iodobenzoic acid of the formula: HO 0

H

2 N * 10 1 CI 2-Amino-5-chloro-3-iodobenzoic acid 'H-NMR (DMSO-d,,TMS) 5 (ppm): 6.76 (2H, brs), 7.75 (1H, d, J=lHz), 7.87 (1H, d, J=lHz). Reference Preparation Example 57-(2) 15 According to the same manner as that of Reference Preparation Example 46- (1), 2-amino-5-chloro-3-iodoben zoic acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 2-[3-bromo-l-(3-chloro-2-pyridinyl)-1H-pyrazol 5-yl)-6-chloro--iodo-4H-3,1-benzoixazine-4-one of the 20 formula: -540 Br N I CI. 2-[3-Bromo-1-(3-chloro-2-pyridinyl)-lH-pyrazol-5-yl]-6 chloro-8-iodo-4H-3,1-benzoxazine-4-one 'H-NMR (DMSO-d 6 , TMS) 6 (ppm) : 7. 53 (1H, s) , 7. 69 (1H, dd, J=8Hz, 5 4Hz), 8.08 (lH, d, J=2Hz), 8.29 (1H, d, J=8Hz), 8.38 (1H, d, J=2Hz), 8.57 (1H, d, J=4Hz). Reference Preparation Example 58 According to the same manner as that of Reference Preparation Example 46- (1), 2-amino-3-methoxybenzoic acid was 10 used in place of 2-amino-3,5-dibromobenzoic acid to obtain 2-(3-bromo-1-(3-chloro-2-pyridinyl)-lH-pyrazol-5-yl]-8 methoxy-4H-3,1-benzoxazine-4-one of the formula: Br N)O N

H

3 CO 2- (3-Bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -8 15 methoxy-4H-3,1-benzoxazine-4-one H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 3.67 (3H, s), 7.40 (1H, dd, J=8Hz, 1Hz), 7.46 (1H, s), 7.52 (1H, t, J=8Hz), 7.61 (1H, dd, J=8Hz, 1Hz), 7.78 (1H, dd, J=8Hz, 4Hz), 8.28 (1H, dd, J=8Hz, 1Hz), 8.57 541 (1H, dd, J=4Hz, 1Hz) Reference Preparation Example 59 According to the same manner as that of Reference Preparation Example 46- (1), 2-amino-3-trifluoromethylbenzoic 5 acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5 yl)-8-trifluoromethyl-4H-3,1-benzoxazine-4-one of the formula: Br CI N N

F

3 C 10 2-[3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-8 trifluoromethyl-48-3,1-benzoxazine-4-one 'H-NMR (DMSO-d,TMS) 6 (ppm): 7.56 (1H, s), 7.69-7.77 (2H, m), 8.15 (1H, d, J=8Hz), 8.29 (1H, dd, J=8Hz, 1Hz), 8.37 (1H, d, J=8Hz), 8.55 (1H, dd, J=4Hz, 1Hz). 15 Reference Preparation Example 60-(1) To a solution of 4.8 g of hydrazine monohydrate in 160 ml of ethanol, 14.2 g of ethyl trifluoroacetate was added dropwise. The resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. 20 The resulting residue was dissolved in 100 ml of ethanol, and 9.9 g of formamidine acetate was added thereto. The mixture was stirred for 3 hours under heat refluxing. The reaction -542 mixture was allowed to cool to room temperature, and then concentrated under reduced pressure. An aqueous sodium bicarbonate solution was poured into the resulting residue, and the mixture was extracted with ethyl acetate two times. The 5 organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 7.0 g of 3-trifluoromethyl-lH-1, 2 , 4 10 triazole of the formula:

F

3 C N, N N H. 3-Trifluoromethyl-1H-1,2,4-triazole 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 8.48 (1H, s). Reference Preparation Example 60-(2) 15 A mixture of 3.5 g of 3-trifluoromethyl-1H-1, 2, 4-triazole, 3.8 g of 2, 3-dichloropyridine, 6.0 g of potassium carbonate and 30 ml of N, N-dimethylformamide was stirred at 120 0 C for 27 hours. After the reaction mixture was allowed to cool to room temperature, water was poured and the mixture was extracted 20 with ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was .543 subjected to silica gel column chromatography to obtain 0.72 g of 3-chloro-2-(3-trifluoromethyl-1H-1, 2 , 4-triazol-1-yl) pyridine of the formula:

F

3 C N ClN 5 3-Chloro-2-(3-trifluoromethyl-lH-1,2,4-triazol-1-yl) pyridine 'H-NMR (DMSO-d,) 5 (ppm): 7.47 (1H, dd, J=8Hz, 5Hz), 8.01 (1H, dd, J,=8Hz, 2Hz), 8.53 (1H, dd, J=5Hz, 2Hz), 8.82 (1H, s). Reference Preparation Example 61-(1) 10 According to the same manner as that of Reference Preparation Example 17, ethylhydrazine was used in place of methylhydrazine to obtain 1-ethyl-3-trifluoromethyl-lH pyrazole of the formula:

F

3 C N CH3 15 1-Ethyl-3-trifluoromethyl-lH-pyrazole 'H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.52 (3H, t, J=7Hz), 4.23 (2H, q, J=7Hz), 6.51 (1H, d, J=2Hz), 7.44 (1H, d, J=2Hz). Reference Preparation Example 61-(2) According to the same manner as that of Reference 20 Preparation Example 18, 1-ethyl-3-trifluoromethyl-1H- ,544 pyrazole was used in place of 1-methyl-3-trifluormethyl-lH pyrazole to obtain 1-ethyl-3-trifluoromethyl-1H-pyrazole-5 carboxylic acid of the formula:

F

3 C N CO 2 H CH3 5 1-Ethyl-3-trifluoromethyl-H-pyrazole-5-carboxylic acid 'H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.51 (3H, t, J=7Hz), 4.68 (2H, q, J=7Hz), 7.21 (1H, s). Reference Preparation Example 61-(3) ,According to the same manner as that of Reference 10 Preparation Example 13, 1-ethyl-3-trifluoromethyl-lH pyrazole-5-carboxylic acid was used in place of 1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxylic acid to obtain 6-chloro-2- (1-ethyl-3-trifluoromethyl-H-pyrazol-5 yl)-8-methyl-4H-3,1-benzoxazine-4-one of the formula:

F

3 C N

H

3 C 15 H 3 C CI 6-Chloro-2- (1-ethyl-3-trifluoromethyl-1H-pyrazol-5-yl) -8 methyl-4H-3, 1-benzoxazine-4-one 'H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.58 (3H, t, J=7Hz), 2.59 (3H, s), 4.89 (2H, q, J=7Hz), 7.33 (1H, s), 7.69 (1H, d, J=2Hz), 8.07 20 (1H, d, J=2Hz).

545 Reference Preparation Example 61-(4) According to the same manner as that of Reference Preparation Example 1, 6-chloro-2- (1-ethyl-3-trifluoromethyl -lH-pyrazol-5-yl) -8-methyl-4H-3, 1-benzoxazine-4-one was used 5 in place of 6-chloro-2-[1-(3-chloro-2-pyridinyl)- 3 trifluoromethyl-lH-pyrazol-5-yl)-8-methyl-4H-3,1 benzoxazine-4-one to obtain N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl)-l-ethyl-3 trifluoromethyl-1H-pyrazole-5-carboxiamide of the formula: H3C CI

F

3 C 0 3 / N,- N N H O N' NH2' 10 H 3 C H N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl] -1-ethyl-3 -trifluoromethyl-1H-pyrazole-5-carboxiamide 1H-NMR (CDCl 3 , TMS) 6 (ppm) : 1. 48 (3H, t, J=7Hz) , 2. 30 (3H, s) , 4.04 (2H, s), 4.66 (2H, q, J=7Hz), 7.08 (1H, s), 7.29 (1H, s), 15 7.40 (lH, s), 7.45 (lH, brs), 9.81 (1H, brs). Reference Preparation Example 62-(l) A mixture of 2.82 g of ethyl 2-(2-chlorobenzoyl)-3-(N,N dimethylamino) acrylate (a compound described in JP-A 7-101940), 1.25 g of tert-butylhydrazine hydrochloride and 10 ml of 20 ethanol was heated to reflux for 8 hours. After the reaction mixture was allowed to cool to room temperature, water was poured and the mixture was extracted with ethyl acetate. The .546 organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.48 g of ethyl 5 1-tert-butyl-5-(2-chlorophenyl)-lH- pyrazole-4-carboxylate of the formula:

N

(H

3

C)

3 C---N

OCH

2

CH

3 'CI 0 Ethyl, 1-tert-butyl-5-(2-chlorophenyl)-lH-pyrazole-4 carboxylate 10 'H-NMR (CDC1 3 ) 6 (ppm): 1.04 (3H, t, J=7Hz), 1.47 (9H, s), 3.98-4.12 (2H, m), 7.28-7.35 (2H, m), 7.38-7.42 (1H, m), 7.45-7.48 (1H, m), 7.99 (1H, s). Reference Preparation Example 62-(2) According to the same manner as that of Reference 15 Preparation Example 54-(2), ethyl 1-tert-butyl-5-(2 7 chlorophenyl)-lH-pyrazole-4-carboxylate was used in place of ethyl 3-(2-chlorophenyl)-1-methyl-1H-pyrazole-4-carboxylate to obtain 1-tert-butyl-5-(2-chlorophenyl)-1H-pyrazole-4 carboxylic acid of the formula: .547

N

(H

3

C)

3 C..--N OH CI 0 1-tert-Butyl-5-(2-chlorophenyl)-lH-pyrazole-4-carboxylic acid 'H-NMR (CDCl 3 ) 6 (ppm): 1.45 (9H, s), 7.25-7.33 (2H, m), 7.39 5 (lH, td, J=7Hz, 2Hz), 7.44 (1H, dd, J=8Hz, 1Hz), 8.00 (1H, s). Reference Preparation Example 62-(3) According to the same manner as that of Reference Preparation Example 54-(3), 1-tert-butyl-5-(2 chlorophenyl) -1H-pyrazole-4-carboxylic acid was used in place 10 of 3- (2-chlorophenyl) -1-methyl-lH-pyrazole-4-carboxylic acid to obtain 2-[1-tert-butyl-5-(2-chlorophenyl)-lH-pyrazol-4 yl]-6-chloro-8-methyl-4H-3,1-benzoxazine-4-one of the formula:

N

(H

3

C)

3 C.N / O 0 C1 N I I

H

3 C CI 15 2-[l-tert-Butyl-5-(2-chlorophenyl)-H-pyrazole-4-yl)-6 chloro-8-methyl-4H-3,1-benzoxazine-4-one H-NMR (DMSO-d 6 ) 6 (ppm): 1.44 (9H, s), 1.77 (3H, s), 7.47-7.59 (3H, m), 7.65-7.68 (2H, m), 7.80 (lH, d, J=2Hz), 8.18 (lH, s). Reference Preparation Example 62-(4) 548 According to the same manner as that of Reference Preparation Example 54-(4), 2-[1-tert-butyl-5-(2 chlorophenyl)-1H-pyrazol-4-yl]-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 6-chloro-2-[3-( 2

-

5 chlorophenyl)-l-methyl-lH-pyrazol- 4 -yl]-8-methyl-4H-3,1 benzoxazine-4-one to obtain 1-tert-butyl-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-5-(2-chlorophenyl)-1H pyrazole-4-carboxamide of the formula:

H

3 C C1 N- / ,N.

(H

3

C)

3 C-N N H C1 O N H 10 1-tert-Butyl-N-[4-chloro-2-(hydrazinocarbonyl)-6 methylphenyl] -5- (2-chlorophenyl) -1H-pyrazole-4-carboxamide 1H-NMR (DMSO-d 6 ) 6 (ppm): 1.40 (9H, s), 2.06 (3H, s), 4.37 (2H, brs), 7.28 (1H, d, J=2Hz), 7.38-7.53 (5H, m), 8.10 (1H, s), 9.36 (1H, brs), 9.53 (lH, brs). 15 Reference Preparation Example 63-(l) A mixture of 4.62 g of chloral hydrate, 3.5 g of 3-chloro-2-methylaniline, 30 g of anhydrous sodium sulfate, 120 ml of water and 2 ml of 2N hydrochloric acid was stirred at room temperature for 2 hours. Then, to the resulting mixture, 20 1. 8 g of hydroxylamine hydrochloride was added, and the mixture was heated to ref lux for 30 minutes. The reaction mixture was 549 ice-cooled, and a deposited precipitate was collected by filtration to obtain 2.5 g of N-(3-chloro-2-methylphenyl)- 2 (hydroxyimino)acetamide of the formula: H HONj N CI. 5 N- (3-chloro-2-methylphenyl) -2- (hydroxyimino) acetamide 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm) : 2.22 (3H, s), 7.22 (1H, t, J=8Hz), 7.33 (1H, d, J=8Hz), 7.38 (1H, d, J=8Hz), 7.67 (1H, s), 9.78 (1H, brs), 12.21 (1H, s). Reference Preparation Example 63-(2) 10 To 2.5 g of concentrated sulfuric acid was added 2.5 g of N-(3-chloro-2-methylphenyl)-2-(hydroxyimino)acetamide at 50"C, and the mixture was stirred at 80*C for 30 minutes. The reaction mixture was poured into 200 g of ice, and a deposited precipitate was collected by filtration to obtain 1.3 g of 15 6-chloro-7-methyl-lH-indole-2,3-dione of the formula: o O HN H3C C1. 6-Chloro-7-methyl-lH-indole-2,3-dione 1 H-NMR (DMSO-d 6 ,TMS) 6 (ppm) : 2.22 (3H, s), 7.15 (1H, d, J=8Hz), 7.37 (1H, d, J=8Hz), 11.28 (1H, s). 20 Reference Preparation Example 63-(3) .550 A mixed solution of 1.3 g of 6-chloro-7-methyl-1H-indole 2,3-dione and 50 ml of a 2N aqueous sodium hydroxide solution was added dropwise to 2 g of aqueous hydrogen peroxide (30%), and the mixture was stirred at room temperature for 1 hour. The' 5 reaction mixture was adjusted to pH 4 by an addition of 2N hydrochloric acid, and a deposited precipitate was collected by filtration to obtain 0.6 g of 2-amino-4-chloro-3 methylbenzoic acid of the formula: HO 0 H2N H3C CI 10 2-Amino-4-chloro-3-methylbenzoic acid 'H-NMR (DMSO-d,,TMS) 5 (ppm): 2.18 (3H, s), 6.62 (lH, d, J=9Hz), 7.61 (1H, d, J=9Hz). Reference Preparation Example 63-(4) According to the same manner as that of Reference 15 Preparation Example 46-(1), 2-amino-4-chloro- 3-methylbenzoic acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 2-[3-bromo-l-(3-chloro-2-pyridinyl)-1H-pyrazol-5 yl]-7-chloro-8-methyl-4H-3,1-benzoxazine-4-one of the formula: 551 Br N0 0 N O

N

1 C1 N N

H

3 C CI 2- [2-Bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl) -7 chloro-8-methyl-4H-3,1-benzoxazine-4-one 1 IH-NMR (DMSO-d 6 ,TMS) 5 (ppm): 1.76 (3H, s), 7.55 (1H, s), 7.65 5 (1H, d, J=9Hz), 7.77 (1H, dd, J=8Hz, 4Hz), 7.94 (1H, d, J=9Hz), 8.35 (1H, dd, J=8Hz, 1Hz), 8.64 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 64-(1) According to the same manner as that of Reference Preparation Example 14, isopropyl iodide was used in place of 10 2, 3-dichloropyridine to obtain 1-isopropyl-3-trifluoromethyl -1H-pyrazole of the formula:

F

3 C N 1-Isopropyl-3-trifluoromethyl-1H-pyrazole 'H-NMR (CDC1 3 ,TMS) 6 (ppm): 1.53 (6H, d, J=7Hz), 4.53-4.60 (1H, 15 m), 6.50 (1H, d, J=2Hz), 7.45 (1H, d, J=2Hz). Reference Preparation Example 64-(2) According to the same manner as that of Reference Preparation Example 18, 1-isopropyl-3-trifluoromethyl-lH pyrazole was used in place of 1-methyl-3-trifluoromethyl- ,552 1H-pyrazole to obtain 1-isopropyl-3-trifluoromethyl-1H pyrazole-5-carboxylic acid of the formula:

F

3 C N,. N CO 2 H 1-Isopropyl-3-trifluoromethyl-1H-pyrazole-5-carboxylic acid 5 1 H-NMR (CDCl 3 , TMS) 6 (ppm) : 1. 53 (6H, d, J=7Hz) , 5. 4 9-5. 56 (1H, m), 7.17 (1H, s). Reference Preparation Example 64-(3) According to the same manner as that of Reference Preparation Example 13, 1-isopropyl-3-trifluoromethyl-lH 10 pyrazole-5-carboxylic acid was used in place of 1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid to obtain 6-chloro-2-(1-isopropyl-3-trifluromethyl-1H-pyrazol 5-yl)-8-methyl-4H-3,1-benzoxazine-4-one of the formula:

F

3 C N.

H

3 C CI 15 6-Chloro-2-(1-isopropyl-3-trifluromethyl-1H-pyrazol-5-yl)-8 -methyl-4H-3,1-benzoxazine-4-one IH-NMR (CDCl 3 ,TMS) 6 (ppm): 1.62 (6H, d, J=7Hz), 2.59 (3H, s), 5.83-5.90 (1H, m), 7.31 (1H, s), 7.68 (1H, s), 8.07 (1H, s). Reference Preparation Example 64-(4) 20 According to the same manner as that of Reference .553 Preparation Example 1, 6-chloro-2-(1-isopropyl- 3 trifluoromethyl-1H-pyrazol-5-yl)-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 6-chloro-2-[1-(3 chloro-2-pyridinyl)-3-trifluoromethyl-lH-pyrazol-5-yl]-8 5 methyl-4H-3,1-benzoxazine-4-one to obtain N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-isopropyl-3-trifluoro methyl-1H-pyrazole-5-carboxiamide of the formula:

H

3 C C1 F3CN N N H NNH2 H N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl]-1 10 isopropyl-3-trifluoromethyl-1H-pyrazole-5-carboxiamide 1 H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 1.44 (6H, d, J=7Hz), 2.25 (3H, s), 4.36 (2H, s), 5.42-5.47 (1H, m), 7.34 (1H, s), 7.36 (lH, s), 7.50 (lH, s), 9.61 (lH, brs), 10.16 (1H, brs). Reference Preparation Example 65 15 According to the same manner as that of Reference Preparation Example 46-(1), 2-amino-3,6-dichlorobenzoic acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 2-[3-bromo-l-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-5,8 dichloro-4H-3,1-benzoxazine-4-one of the formula: .554 Br N, \O O N) CI N / C1 N C1 2- [3-Bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl] -5, 8 dichloro-4H-3,1-benzoxazine-4-one 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 7.57 (1H, s), 7.62 (1H, d, J=8Hz), 5 7.72 (lH, dd, J=8Hz, 4Hz), 7.87 (1H, d, J=8Hz), 8.31 (1H, d, J=8Hz), 8.59 (lH, d, J=4Hz). Reference Preparation Example 66-(1) According to the same manner as that of Reference Preparation Example 63- (1), 5-chloro-2-methylaniline was used 10 in place of 3-chloro-2-methylaniline to obtain N-(5-chloro-2 methylphenyl) -2- (hydroxyimino) acetamide of the formula: H HO Nn N > r CI N- (5-Chloro-2-methylphenyl) -2- (hydroxyimino) acetamide 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 2.20 (3H, s), 7.17 (lH, dd, J=8Hz, 15 2Hz), 7.27 (1H, d, J=8Hz), 7.64 (lH, d, J=2Hz), 7.70 (1H, d, J=2Hz), 9.56 (lH, s), 12.27 (1H, s). Reference Preparation Example 66-(2) According to the same manner as that of Reference Preparation Example 63-(2), N-(5-chloro-2-methylphenyl)-2 20 (hydroxyimino)acetamide was used in place of N-(3-chloro- 555 2-methylphenyl) -2- (hydroxyimino) acetamide to obtain 4-chloro-7-methyl-1H-indole-2,3-dione of the formula: 0 O HN CI 1 H3C r. 4-Chloro-7-methyl-lH-indole-2, 3-dione 5 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 2.16 (3H, s), 6.99 (1H, d, J=8Hz), 7.40 (1H, d, J=8Hz), 11.24 (1H, s). Reference Preparation Example 66-(3) According to the same manner as that of Reference Preparation Example 63- (3) , 4-chloro-7-methyl-lH-indole-2, 3 10 dione was used in place of 6chloro-7-methyl-lH-indole-2,3 dione to obtain 2-amino-6-chloro-3-methylbenzoic acid of the formula: HO 0 H2N Cl

H

3 C . 2-Amino-6-chloro-3-methylbenzoic acid 15 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 2.07 (3H, s), 6.57 (1H, d, J=8Hz), 7.01 (1H, d, J=8Hz). Reference Preparation Example 66-(4) According to the same manner as that of Reference Preparation Example 46-(1), 2-amino-6-chloro-3-methylbenzoic 20 acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 2-(3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazol-5- 556 yl]-5-chloro-8-methyl-4H-3,1-benzoxazine-4-one of the formula: Br N 3C. 2-[3-Bromo-1-(3-chloro-2-pyridinyl)-lH-pyrazol-5-yl)-5 5 chloro-8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (DMSO-d ,TMS) 6 (ppm): 1.66 (3H,s), 7.52-7.56 (2H, m), 7.62 (1H, d, J=8Hz), 7.76 (1H, dd, J=8Hz, 4Hz), 8.34 (1H, d, J=8Hz), 8.63 (lH, d, J=4Hz). Reference Preparation Example 67-(1) 10 To a mixture of 5 g of 4-ethoxy-1,1,1-trifluoro-3-butene 2-one, 3 g of sodium acetate and 15 ml of ethanol was added 4. 6 g of tert-butylhydrazine hydrochloride, and the mixture was heated to reflux for 2 days. Water was added to the reaction mixture, and the mixture was extracted with diethyl ether three 15 times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 3.0 g of 1-tert-butyl-3-trifluoromethyl-1H-pyrazole of the formula:

F

3 C 20 .

.557 1-tert-Butyl-3-trifluoromethyl-1H-pyrazole 1 H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.61 (9H, s), 6.48 (1H, d, J=2Hz), 7.54 (1H, d, J=2Hz) Reference Preparation Example 67-(2) 5 According to the same manner as that of Reference Preparation Example 18, 1-tert-butyl-3-trifluoromethyl-lH pyrazole was used in place of 1-methyl-3-trifluoromethyl-lH pyrazole to obtain 1-tert-butyl-3-trifluoromethyl-1H pyrazole-5-carboxylic acid of the formula:

F

3 C N1 CO 2 H 10+I 1-tert-Butyl-3-trifluoromethyl-1H-pyrazole-5-carboxylic acid 'H-NMR (CDC1,TMS) 5 (ppm): 1.75 (9H, s), 7.28 (1H, s). Reference Preparation Example 67-(3) 15 According to the same manner as that of Reference Preparation Example 13, 1-tert-butyl-3-trifluoromethyl-1H pyrazole-5-carboxylic acid was used in place of 1-(3-chloro 2-pyridinyl)-1H-pyrazole-5-carboxylic acid to obtain 6-chloro-2-(1-tert-butyl-3-trifluoromethyl-1H-pyrazol-5-yl) 20 -8-methyl-4H-3,1-benzoxazine-4-one of the formula: ,558

F

3 C N

H

3 C CI 6-Chloro-2-(1-tert-butyl-3-trifluoromethyl-lH-pyrazol-5-yl) -8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.86 (9H, s), 2.61 (3H, s), 7.32 5 (1H, s), 7.68 (1H, d, J=2Hz), 8.08 (1H, d, J=2Hz). Reference Preparation Example 67-(4) According to the same manner as that of Reference Preparation Example 1, 6-chloro-2-(1-tert-butyl-3 trifluoromethyl-1H-pyrazol-5-yl)-8-methyl-4H-3,1 10 benzoxazine-4-one was used in place of 6-chloro-2-[1-(3 chloro-2-pyridinyl)-3-trifluoromethyl-lH-pyrazol-5-yl]-8 methyl-4H-3,1-benzoxazine-4-one to obtain N-(4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(2-tert-butyl)-3 trifluoromethyl-1H-pyrazole-5-carboxiamide of the formula:

F

3 C

H

3 C C1 F3 0/ N, - N N HNH2 15 0 H N-(4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl]-1-tert butyl-3-trifluoromethyl-lH-pyrazole-5-carboxiamide 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 1.67 (9H, s), 2.27 (3H, s), 4.36 (2H, s), 7.11 (1H, s), 7.34 (1H, s), 7.48 (1H, s), 9.63 (1H, 559 brs), 10.22 (1H, brs). Reference Preparation Example 68-(1) According to the same manner as that of Reference Preparation Example 24, tert-butylhydrazine hydrochloride was 5 used in place of 2-chlorophenylhydrazine hydrochloride to obtain 1-tert-butyl-3-(2-furyl)-5-trifluoromethyl-1H pyrazole of the formula:

F

3 C 1-tert-Butyl-3-(2-furyl)-5-trifluoromethyl-1H-pyrazole 10 IH-NMR (CDC1 3 ,TMS) 6 (ppm): 1.53 (9H, s), 6.48-6.51 (2H, m), 6.59 (1H, s), 7.55 (1H, dd, J=2Hz, 1Hz). Reference Preparation Example 68-(2) According to the same manner as that of Reference Preparation Example 25, 1-tert-butyl-3-(2-furyl)-5 15 trifluoromethyl-1H-pyrazole was used in place of 1-(2 chlorophenyl)-5-(2-furyl)-3-trifluoromethyl-1H-pyrazole to obtain 1-tert-butyl-5-trifluoromethyl-lH-pyrazole-3 carboxylic acid of the formula:

F

3 C CO 2 H 20 1-tert-Butyl-5-trifluoromethyl-lH-pyrazole-3-carboxylic acid 560 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.73 (911, s), 7.90 (1H, brs). Reference Preparation Example 68-(3) According to the same manner as that of Reference Preparation Example 13, 1-tert-butyl-5-trifluoromethyl-lH 5 pyrazole-3-carboxylic acid was used in place of 1-(3-chloro 2-pyridinyl) -1H-pyrazole-5-carboxylic acid to obtain 6-chloro-2-[1-tert-butyl-5-trifluoromethyl-1H-pyrazol- 3 -yl] -8-methyl-4H-3,1-benzoxazine-4-one of the formula: N .

H

3 C 5 . 10 6-Chloro-2-[1-tert-butyl-5-trifluoromethyl-lH-pyrazol- 3 -yl] -8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.76 (9H, s), 2.58 (3H, s), 7.57 (lH, s), 7.74 (1H, d, J=2Hz), 8.12 (lH, d, J=2Hz). Reference Preparation Example 68-(4) 15 According to the same manner as that of Reference Preparation Example 1, 6-chloro-2-(l-tert-butyl-5 trifluoromethyl-1H-pyrazol-3-yl)-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 6-chloro-2-[1-(3 chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazol-5-yl]-8 20 methyl-4H-3,1-benzoxazine-4-one to obtain N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-tert-butyl-5 trifluoromethyl-1H-pyrazole-3-carboxamide of the formula: ,561 H3C CI F3C 0/ >N, N N H O N'NH2 H N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl] -1-tert butyl-5-trifluoromethyl-lH-pyrazole-3-carboxamide 1 H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 1.70 (9H, s), 2.26 (3H, s), 4.39 5 (2H, s), 7.37 (1H, s), 7.50 (1H, s), 7.85 (1H, s), 9.75 (1H, brs), 10.67 (1H, brs). Reference Preparation Example 69 According to the same manner as that of Reference Preparation Example 46-(l), 2-amino-3-methylbenzoic acid was 10 used in place of 2-amino-3,5-dibromobenzoic acid to obtain 2-(3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-8 methyl-4H-3,1-benzoxazine-4-one of the formula: Br NO Clt N

N

3 C 2-[3-Bromo-1-(3-chloro-2-pyridinyl)-lH-pyrazol-5-yl]-8 15 methyl-4H-3,1-benzoxazine-4-one 1H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 1.74 (3H, s), 7.46-7.51 (2H, m), 7.68 (1H, d, J=8Hz), 7.76 (1H, dd, J=8Hz, 4Hz), 7.94 (1H, d, J=8Hz), 8.35 (1H, dd, J=8Hz, 1Hz), 8.63 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 70 ,562 According to the same manner as that of Reference Preparation Example 46-(l), 2-amino-3-bromobenzoic acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 8-bromo-2-[3-bromo-1-(3-chloro-2-pyridinyl)-lH-pyrazol-5-yl 5 ]-4H-3,1-benzoxazine-4-one of the formula: Br N, yo N Br. 8-Bromo-2-[3-bromo-1-(3-chloro-2-pyridinyl)-lH-pyrazol-5-yl ]-4H-.3,1-benzoxazine-4-one 1 H-NMR (DMSO-d 6 ,TMS) 5 (ppm):.7.49 (1H, t, J=8Hz), 7.54 (1H, 10 s), 7.72 (1H, dd, J=8Hz, 4Hz), 8.08 (1H, s), 8.10 (1H, s), 8.32 (lH, t, J=4Hz), 8.60 (1H, d, J=4Hz). Reference Preparation Example 71-(1) A mixture of 1.0 g of pyrrole, 3.0 g of 3-chloro-2-methanesulfonylpyridine, 6.6 g of cesium carbonate 15 and 10 ml of N,N-dimethylformamide was stirred at 60 0 C for 27 hours. After the reaction mixture was allowed to cool to room temperature, water was poured and the mixture was extracted with ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium 20 chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 1.7 g ,563 , of 3-chloro-2-(lH-pyrrol-1-yl)pyridine of the formula: N CI N 3-Chloro-2- (1H-pyrrol-1-yl) pyridine 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 6.35 (2H, t, J=2Hz), 7.15 (1H, dd, 5 J=8Hz, 5Hz), 7.42 (2H, t, J=2Hz), 7.83 (1H, dd, J=8Hz, 2Hz), 8.39 (1H, dd, J=5Hz, 2Hz). Reference Preparation Example 71-(2) To 3.8 ml of N,N-dimethylformamide was added dropwise 4.2 ml of, phosphorus oxychloride at room temperature, and the 10 mixture was stirred at room temperature for 30 minutes. Thereto 1.6 g of 3-chloro-2-(lH-pyrrol-1-yl)pyridine was added, and the resulting mixture was stirred at 60 0 C for 2 hours. The reaction mixture was allowed to cool to room temperature, and then slowly added to ice-water. The mixture was adjusted to 15 pH 4 by an addition of a 2N aqueous sodium hydroxide solution. A deposited precipitate was collected by filtration to obtain 1.7 g of 3-chloro-2-(2-formyl-1H-pyrrol-1-yl)pyridine of the formula: N "CHO 20 3-Chloro-2-(2-formyl-1H-pyrrol-1-yl)pyridine 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 6.48 (1H, dd, J=4Hz, 3Hz), 564% 7.14-7.15 (2H, m), 7.39 (1H, dd, J=8Hz, 5Hz), 7.89 (1H, dd, J=8Hz, 2Hz), 8.47 (1H, dd, J=5Hz, 2Hz), 9.57 (18, d, J=lHz). Reference Preparation Example 71-(3) To a solution of 1.5 g of 3-chloro-2-(2-formyl-1H-pyrrol-' 5 1-yl)pyridine in 20 ml'of N,N-dimethylformamide,1.3 g of N-bromosuccinimide was added. The mixture was stirred at room temperature for 3 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 1.9 g of 4-bromo-1-(3-chloro-2-pyridinyl) 10 -lH-pyrrole-2-carbaldehyde of the formula: Br N CHO Cl NN 4-Bromo-1- (3-chloro-2-pyridinyl)-lH-pyrrole-2-carbaldehyde 'H-NMR (CDC1 3 , TMS) 5 (ppm) : 7. 11 (1H, d, J=2Hz) , 7. 14 (1H, dd, J=2Hz, 1Hz), 7.41 (18, dd, J=8Hz, 5Hz), 7.89 (1H, dd, J=8Hz, 15 2Hz), 8.46 (1H, dd, J=5Hz, 2Hz), 9.51 (1H, d, J=lHz). Reference Preparation Example 71-(4) An aqueous solution of 1.2 g of potassium permanganate in 10 ml of water was added dropwise to a mixture of 0.72 g of 4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carbaldehyde 20 and 15 ml of acetone while the mixture was retained at 40*C. The mixture was then stirred at 60 0 C for 8 hours. Precipitates were filtered off to obtain a filtrate. The filtrate was 565 1 adjusted to pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution, and then washed with chloroform two times. The aqueous layer was adjusted to around pH 3 by an addition of 2N hydrochloric acid. A deposited precipitate was collected 5 by filtration to obtain 0.56 g of 4-bromo-1-(3-chloro- 2 pyridinyl)-1H-pyrrole-2-carboxylic acid of the formula: Br N CO 2 H 4-Bromo-1-(3-chloro-2-pyridinyl)-lH-pyrrole-2-carboxylic acid 10 'H-NMR (DMSO-d 6 , TMS) 8 (ppm): 6. 99 (1H, d, J=2Hz) , 7. 38 (lH, d, J=2Hz), 7.56 (lH, dd, J=8Hz, 5Hz), 8.10 (1H, dd, J=8Hz, 2Hz), 8.48 (1H, dd, J=5Hz, 2Hz). Reference Preparation Example 71-(5) A mixture of 0. 56 g of 4-bromo-1- (3-chloro-2-pyridinyl) 15 1H-pyrrole-2-carboxylic acid and 0.40 ml of thionyl chloride was heated to reflux in acetonitrile for 2 hours. The reaction mixture was allowed to cool to room temperature, and then concentrated under reduced pressure. The resulting residue was dissolved in 10 ml of acetonitrile. Thereto 0.35 g of 20 2-amino-5-chloro-3-methylbenzoic acid was added, and the resulting mixture was stirred at room temperature for 10 minutes. To the mixture, 0.53 ml of pyridine was added, and -566 the mixture was stirred at room temperature for 6 hours. Then 0.19 ml of methanesulfonyl chloride was added, and the mixture was stirred at room temperature for 1 hour. Water was poured into the reaction mixture, and a deposited precipitate was 5 collected by filtration to obtain 0.29 g of 2-[4-bromo-1 (3-chloro-2-pyridinyl) -1H-pyrrol-2-yl] -6-chloro-8-methyl-4H -3,1-benzoxazine-4-one of the formula: Br N

,H

3 C 2-[4-Bromo-l-(3-chloro-2-pyr.idinyl) -1H-pyrrol-2-yl]-6 10 chloro-8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.73 (3H, s), 7.07 (1H, d, J=2Hz), 7.32 (1H, d, J=2Hz), 7.42-7.44 (2H, m), 7.91 (1H, dd, J=8Hz, 2Hz), 7.93 (1H, d, J=2Hz), 8.51 (1H, dd, J=5Hz, 2Hz). Reference Preparation Example 71-(6) 15 A mixture of 0.29 g of 2-[4-bromo-1-(3-chloro-2 pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one, 0.10 g of hydrazine monohydrate and 10 ml of tetrahydrofuran was stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was 20 extracted with ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and -567 concentrated under reduced pressure to obtain 0.30 g of 4-bromo-N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl -1 - (3-chloro-2-pyridinyl) -1H-pyrrole-2-carboxamide of the formula:

H

3 C CI Br O 0 N 4JKN N H 5 4-Bromo-N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl] -1 -(3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxamide 1 H-NMR (CDCl 3 ,TMS) 6 (ppm): 2.20 (3H,s), 4.04 (2H, brs), 7.02 (1H, d, J=2Hz), 7.04 (lH, d, J=2Hz), 7.21 (1H, d, J=2Hz), 7.28 10 (1H, d, J=2Hz), 7.31 (1H, dd, J=8Hz, 5Hz), 7.34 (1H, brs), 7.80 (1H, dd, J=8Hz, 2Hz), 8.41 (1H, dd, J=5Hz, 2Hz), 9.27 (1H, brs). Reference Preparation Example 72 A mixture of 0.60 g of 2-[3-bromo-l-(3-chloro-2 pyridinyl) -1H-pyrazol-5-yl] -6-chloro-8-methyl-4H-3, 1 15 benzoxazine-4-one, 0.29 g of isopropylhydrazine hydrochloride, 0.27 g of triethylamine and 6 ml of tetrahydrofuran was stirred at room temperature for 3 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate two times. The combined organic layer was washed with 20 an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column 568 chromatography to obtain 0.35 g of 3-bromo-N-[4-chloro- 2 (N' -isopropylhydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro -2-pyridinyl)-lH-pyrazole-5-carboxamide of the formula: Br

H

3 C' Ci BNN N H N H Ci 0 N CH(CH 3

)

2 H 5 3-Bromo-N-[4-chloro-2-(N'-isopropylhydrazinocarbonyl)-6 methylphenyl) -1- (3-chloro-2-pyridinyl) -1H-pyrazole-5 carbo xamide 1 H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.,08 (6H, d, J=6Hz), 2.11 (3H, s), 3.12 (lH, hept., J=6Hz), 4.60 (lH, brs), 7.11 (lH, s), 7.14 (1H, 10 d, J=2Hz), 7.20 (lH, d, J=2Hz), 7.37 (1H, dd, Ji=8Hz, J 2 =4Hz), 7.79 (1H, brs), 7.84 (1H, dd, Ji=8Hz, J 2 =lHz), 8.44 (lH, dd, J=4Hz, 1Hz), 9.93 (lH, brs). Reference Preparation Example 73-(1) According to the same manner as that of Reference 15 Preparation Example 20, N-iodosuccinimide was used in place of 1,2-dibromo-1,1,2,2-tetrachloroethane to obtain N,N-dimethyl-5-iodo-H-pyrazole-l-sulfonamide of the formula: N7/ 'N SO2N(CH3)2.

.569 N, N-dimethyl-5-iodo-lH-pyrazole-1-sulfonamide 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 3.07 (6H, s), 6.60 (1H, d, J=lHz), 7.62 (1H, d, J=lHz). Reference Preparation Example 73-(2) 5 According to the same manner as that of Reference Preparation Example 21, N,N-dimethyl-5-iodo-lH-pyrazole-l sulfonamide was used in place of 5-bromo-N,N-dimethyl-lH pyrazole-l-sulfonamide to obtain 3-iodo-lH-pyrazole of the formula: N , 10 H 3-Iodo-lH-pyrazole H-NMR (CDCl 3 ,TMS) 6 (ppm): 6.74 (1H, d, J=3Hz), 8.10 (1H, d, J=3Hz). Reference Preparation Example 73-(3) 15 According to the same manner as that of Reference Preparation Example 22, 3-iodo-1H-pyrazole was used in place of 3-bromo-lH-pyrazole to obtain 3-chloro-2-(3-iodo-1H pyrazol-1-yl)pyridine of the formula: N5 2N 20 3-Chloro-2-(3-iodo-1H-pyrazol-1-yl)pyridine .570 H-NMR (CDC1 3 ,TMS) 6 (ppm): 6.65 (1H, d, J=2Hz), 7.31 (1H, dd, J=8Hz, 4Hz), 7.91 (1H, dd, J=BHz, 1Hz), 7.95 (1H, d, J=2Hz), 8.46 (lH, dd, J=4Hz, 1Hz). Reference Preparation Example 73-(4) 5 According to the same manner as that of Reference Preparation Example 23, 3-chloro-2-(3-iodo-1H-pyrazol-1 yl)pyridine was used in place of 2-(3-bromo-lH-pyrazol-1-yl) 3-chloropyridine to obtain 1-(3-chloro-2-pyridinyl)-3-iodo 1H-pyrazole-5-carboxylic acid of the formula: N'N CO 2 H 10 1-(3-Chloro-2-pyridinyl)-3-iodo-1H-pyrazole-5-carboxylic acid 'H-NMR (CDC1 3 ,TMS) 6 (ppm): 7.20 (1H, s), 7.44 (lH, dd, J=8Hz, 4Hz), 7.91 (1H, dd, J=BHz, 1Hz), 8.50 (1H, dd, J=4Hz, 1Hz). 15 Reference Preparation Example 73-(5) According to the same manner as that of Reference Preparation Example 13, 1-(3-chloro-2-pyridinyl)-3-iodo-1H pyrazole-5-carboxylic acid was used in place of 1-(3-chloro 2-pyridinyl)-lH-pyrazole-5-carboxylic acid to obtain 20 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-iodo-1H-pyrazol-5-yl ]-8-methyl-4H-3,1-benzoxazine-4-one of the formula: 571' , 0 0 CI NNI

H

3 C 6-Chloro-2- [1- (3-chloro-2-pyridinyl) -3-iodo-1H-pyrazol-5-yl ]-8-methyl-4H-3,1-benzoxazine-4-one 1H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.82 (3H, s), 7.39 (1H, s), 5 7.47-7.50 (2H, m), 7.95-7.98 (2H, m), 8.56 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 73-(6) According to the same manner as that of Reference Preparation Example 7, 6-chloro-2- [1- (3-chloro-2-pyridinyl) 3-iodo-1H-pyrazol-5-yl] -8-methyl-4H-3, 1-benzoxazine-4-one 10 was used in place of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-1H pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine-4-one to obtain N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl] -1- (3 chloro-2-pyridinyl)-3-iodo-1H-pyrazole-5-carboxamide of the formula:

H

3 C Cl N .N N H ,NH2 Cl O N N H 15 N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl)-1-(3 chloro-2-pyridinyl)-3-iodo-1H-pyrazole-5-carboxamide 1 H-NMR (DMSO-d 6 ) 5 (ppm): 2.13 (3H, s), 4.36 (2H, brs), 7.31 572 (1H, brs), 7.42 (1H, brs), 7.46 (1H, brs), 7.59 (1H, dd, J=8Hz, 4Hz), 8.15 (1H, d, J=8Hz), 8.49 (1H, dd, J=4Hz, 1Hz), 9.54 (1H, brs), 10.20 (1H, brs). Reference Preparation Example 74-(1) 5 According to the same manner as that of Reference Preparation Example 22, 4-bromo-1H-pyrazole was used in place of 3-bromo-1H-pyrazole to obtain 2-(4-bromo-lH-pyrazol-l yl)-3-chloropyridine of the formula: Br N N 10 2-(4-Bromo-1H-pyrazol-1-yl)-3-chloropyridine 1 H-NMR (CDCl 3 ,TMS) 6 (ppm): 7.31 (1H, dd, J=8Hz, 4Hz), 7.77 (1H, s), 7.92 (1H, dd, J=8Hz, 1Hz), 8.19 (1H, s), 8.45 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 74-(2) 15 According to the same manner as that of Reference Preparation Example 23, 2-(4-bromo-1H-pyrazol-1-yl)-3 chloropyridine was used in place of 2-(3-bromo-1H-pyrazol 1-yl) -3-chloropyridine to obtain 4-bromo-1- (3-chloro-2 pyridinyl)-lH-pyrazole-5-carboxylic acid of the formula: .573 Br 'N CC 2 H CIN 4-Bromo-1-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid 'H-NMR (DMSO-d 6 ) 8 (ppm): 7.66 (1H, dd, J=8Hz, 4Hz), 8.06 (1H, 5 s), 8.23 (1H, dd, J=8Hz, 1Hz), 8.54 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 74-(3) According to the same manner as that of Reference Preparation Example 13, 4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic 10 acid was used in place of 1-(3-chloro-2-pyridinyl)-1H pyrazole-5-carboxylic acid to obtain 2-[4-bromo-1-(3 chloro-2-pyridinyl)-lH-pyrazol-5-yl)-6-chloro-8-methyl-4H-3 ,1-benzoxazine-4-one of the formula: Br N, 0 0 N 1 \ C N/ N

H

3 C C1 15 2- [4-Bromo-l--(3-chloro-2-pyr.dinyl)-1H-pyrazol-5-yl)-6 chloro-8-methyl-4H-3,1-benzoxazine-4-one 1 H-NMR (CDCl 3 , TMS) 5 (ppm): 2. 00 (3H, s) , 7. 4 6 (1H, dd, J=8Hz, 4Hz), 7.53 (1H, d, J=2Hz), 7.87 (1H, s), 7.95 (1H, dd, J=8Hz, 1Hz), 7.98 (1H, d, J=2Hz), 8.51 (lH, dd, J=4Hz, 1Hz).

574 Reference Preparation Example 74-(4) According to the same manner as that of Reference Preparation Example 7, 2-[4-bromo-1-(3-chloro-2-pyridinyl) 1H-pyrazol-5-yl) -6-chloro-8-methyl-4H-3, 1-benzoxazine-4-one' 5 was used in place of 6-chloro-2-[1-(3-chloro-2-pyridinyl) 1H-pyrazol-5-yl] -8-methyl-4H-3, 1-benzoxazine-4-one to obtain 4-bromo-N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl] -1 - (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide of the formula:

H

3 C Br 0 CI N N" N H -NH 2 CI O N "N H 10 4-Bromo-N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyll]-1 - (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide 1 H-NMR (DMSO-d 6 ) 6 (ppm): 2.1'3 (3H, s), 4.47 (2H, brs), 7.37 (lH, s), 7.48 (1H, s), 7.62 (lH, dd, J=8Hz, 4Hz), 8.12 (1H, s), 15 8.19 (1H, d, J=8Hz), 8.50 (1H, d, J=4Hz), 9.69 (1H, brs), 10.24 (1H, brs) Reference Preparation Example 75-(1) According to the same manner as that of Reference Preparation Example 22, 3-phenyl-1H-pyrazole was used in place 20 of 3-bromio-1H-pyrazole to obtain 3-chloro-2-(3-phenyl-1H pyrazol-1-yl)pyridine of the formula: 575 N 'N 3-Chloro-2-(3-phenyl-lH-pyrazol-1-yl)pyridine H-NMR (CDCl 3 ,TMS) 5 (ppm): 6.82 (1H, d, J=2Hz), 7.27 (1H, dd, J=8Hz, 4Hz), 7.35 (1H, m), 7.43 (2H, m), 7.93 (3H, m), 8.20 (1H, 5 d, J=2Hz), 8.48 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 75-(2) According to the same manner as that of Reference Preparation Example 23, 3-chloro-2-(3-phenyl-1H-pyrazol-1 yl)pyridine was used in place of 2-(3-bromo-1H-pyrazol-1-yl) 10 3-chloropyridine to obtain 1-(3-chloro-2-pyridinyl)-3 phenyl-lH-pyrazole-5-carboxylic acid of the formula: N'N CO 2 H CI N 1-(3-Chloro-2-pyridinyl)-3-phenyl-1H-pyrazole-5-carboxylic acid 15 1H-NMR (DMSO-ds) 6 (ppm): 7.36-7.45 (3H, m), 7.57 (1H, s), 7.67 (1H, dd, J=8Hz, 4Hz), 7.90-7.92 (2H, m), 8.24 (1H, dd, J=8Hz, 1Hz), 8.57 (1H, dd, J=4Hz, 1Hz).

576 , Reference Preparation Example 75-(3) According to the same manner as that of Reference Preparation Example 13, 1-(3-chloro-2-pyridinyl).-3-phenyl 1H-pyrazole-5-carboxylic acid was used in place of 5 1-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxylic acid to obtain 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-phenyl-lH pyrazol-5-y1]-8-methyl-4H-3,1-benzoxazine-4-one of the formula: , 0 0 'N C1 N N &CI H3 CI H 3 C 10 6-Chloro-2-[1-(3-chloro-2-pyridinyl)-3-phenyl-lH-pyrazol- 5 yl]-8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.83 (3H, s), 7.39-7.52 (5H, m), 7.59 (1H, s), 7.92-8.00 (4H, m), 8.59 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 75-(4) 15 According to the same manner as that of Reference Preparation Example 7, 6-chloro-2- [1- (3-chloro-2-pyridinyl) 3-phenyl-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine-4-one was used in place of 6-chloro-2- [1- (3-chloro-2-pyridinyl) -lH pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine-4-one to obtain 20 N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl]-l-(3~ chloro-2-pyridinyl)-3-phenyl-lH-pyrazole-5-carboxamide of 577 the formula:

H

3 C C1 0 N NI 'N H NH2 CG O N N H N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl) -1- (3 chloro-2-pyridinyl)-3-phenyl-lH-pyrazole-5-carboxamide 5 'H-NMR (DMSO-d 6 ) 5 (ppm): 2.19 (3H, s), 4.40 (2H, brs), 7.33 (1H, d, J=2Hz), 7.42-7.92 (4H, m), 7.60 (1H, dd, J=8Hz, 4Hz), 7.70 (1H, s), 7.88 (2H, d, J=7Hz), 8.17 (1H, d, J=8Hz), 8.53 (lH, d, J=4Hz), 9.58 (lH, brs,), 10.27 (1H, brs). Reference Preparation Example 76-(l) 10 To a mixture of 4.0 g of N,N-dimethyl-1H-pyrazole-1 sulfonamide and 45 ml of tetrahydrofuran was added dropwise 15.7 ml of a 1.6M n-butyl lithium solution in hexane at -78 0 C, and the mixture was stirred at -78*C for 10 minutes. After 2.3 ml of dimethyl disulfide was added to the mixture, the mixture 15 was stirred for 4 hours while the reaction temperature was gradually returned to room temperature. Water was poured into the reaction mixture, and the mixture was extracted with methyl t-butyl ether three times. The combined organic layer was washed successively with a 1N aqueous sodium hydroxide solution 20 and an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure.

,578 The resulting residue was subjected to silica gel column chromatography to obtain 4.87 g of N,N-dimethyl-5-methylthio-lH-pyrazole-l- sulfonamide of the formula: N -N

SCH

3 5

SO

2

N(CH

3

)

2 N,N-dimethyl-5-methylthio-1H-pyrazole-1-sulfonamide 1 H-NMR (CDCl 3 ,TMS) 5 (ppm): 2.49 (3H, s), 3.01 (6H, s), 6.10 (lH, d, J=2Hz), 7.63 (1H, d, J=2Hz). Reference Preparation Example 76-(2) 10 According to the same manner as that of Reference Preparation Example 21, N,N-dimethyl-5-methylthio-lH pyrazole-1-sulfonamide was used in place of 5-bromo-N,N-dimethyl-lH-pyrazole-1-sulfonamide to obtain 3-methylthio-lH-pyrazole of the formula:

H

3 CS N %N 15 H 3-Methylthio-1H-pyrazole 1 H-NMR (CDCl,TMS) 5 (ppm): 2.61 (3H, s), 6.45 (1H, d, J=3Hz), 8.19 (lH, d, J=3Hz). Reference Preparation Example 76-(3) 20 According to the same manner as that of Reference Preparation Example 22, 3-methylthio-lH-pyrazole was used in 579 place of 3-bromo-1H-pyrazole to obtain 3-chloro-2-(3 methylthio-1H-pyrazol-1-yl)pyridine of the formula:

H

3 CS N N'N 3-Chloro-2- (3-methylthio-lH-pyrazol-1-yl) pyridine 5 IH-NMR (CDCl 3 ,TMS) 6 (ppm): 2.61 (3H, s), 6.40 (1H, d, J=2Hz), 7.25 (1H, dd, J=8Hz, 4Hz), 7.89 (1H, dd, J=8Hz, 1Hz), 8.12 (1H, d, J=2Hz), 8.43 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 76-(4) According to the same manner as that of Reference 10 Preparation Example 23, 3-chloro-2- (3-methylthio-1H-pyrazol 1-yl) pyridine was used in place of 2- (3-bromo-1H-pyrazol-1-yl) -3-chloropyridine to obtain 1-(3-chloro-2-pyridinyl)-3 methylthio-lH-pyrazole-5-carboxylic acid of the formula:

H

3 CS 'N CO 2 H CI N 15 1-(3-Chloro-2-pyridinyl)-3-methylthio-1H-pyrazole-5 carboxylic acid H-NMR (DMSO-d 6 ) 6 (ppm): 2.49 (3H, s), 7.02 (lH, s), 7.62 (1H, dd, J=8Hz, 4Hz), 8.19 (1H, dd, J=8Hz, 1Hz), 8.51 (1H, dd, J=4Hz, 1Hz).

.580 Reference Preparation Example 76-(5) According to the same manner as that of Reference Preparation Example 13, 1- (3-chloro-2-pyridinyl) -3 methylthio-lH-pyrazole-5-carboxylic acid was used in place of' 5 1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid to obtain 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-methylthio 1H-pyrazole-5-yl-8-methyl-4H- 3 , 1-benzoxazine-4-one of the formula:.

H

3 CS N, N 0 0 N O CI , N/ N c

H

3 C 10 6-Chloro-2- [1- (3-chloro-2-pyridinyl) -3-methylthio-lH pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.81 (3H, s), 2.61 (3H, s), 7.15 (lH, s), 7.45-7.48 (2H, m), 7.94-7.98 (2H, m), 8.56 (1H, d, J=4Hz). 15 Reference Preparation Example 76-(6) According to the same manner as that of Reference Preparation Example 7, 6-chloro-2- [1- (3-chloro-2-pyridinyl) 3-methylthio-lH-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine-4 -one was used in place of 6-chloro-2-[1-(3-chloro-2 20 pyridinyl)-1H-pyrazol-5-yl]-8-methyl-4H- 3 ,1-benzoxazine-4 one to obtain N-[4-chloro-2-(hydrazinocarbonyl)-6- 581 , methylphenyl] -1- (3-chloro-2-pyridinyl) -3-methylthio-1H pyrazole-5-carboxamide of the formula: H3C C

H

3 CS O / C N N H CI O N "N H N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl] -1- (3 5 chloro-2-pyridinyl)-3-methylthio-1H-pyrazole-5-carboxamide IH-NMR (DMSO-d 6 ) 6 (ppm): 2.14 (3H, s), 2.53 (3H, s), 4.37 (2H, brs), 7.20 (1H, s), 7.30 (lH, s), 7.46 (1H, s), 7.56 (1H, dd, J=8Hz, 4Hz), 8.12 (1H, d, J=8Hz), 8.47 (1H, d, J=4Hz), 9.54 (1H, brs), 10.16 (1H, brs). 10 Reference Preparation Example 77-(1) To a mixture of 0.50 g of 1-(3-chloro-2-pyridinyl)-3 methylthio-lH-pyrazole-5-carboxylic acid and 5 ml of trifluoroacetic acid was added 0.4 ml of 30% aqueous hydrogen peroxide, and the resulting mixture was stirred at room 15 temperature for 4 hours. Water was poured into the reaction mixture, and the mixture was extracted with methyl t-butyl ether three times. The combined organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced 20 pressure to obtain 0.44 g of 1-(3-chloro-2-pyridinyl)-3 methylsulfonyl-lH-pyrazole-5-carboxylic acid of the formula: 582

H

3 C\ ,O HA 0 N, 'N CO 2 H CIN 1- (3-Chloro-2-pyridinyl) -3-methylsulfonyl-1H-pyrazole-5 carboxylic acid 'H-NMR (DMSO-d 6 ) 5 (ppm): 3.39 (3H, s), 7.57 (1H, s), 7.75 (1H, 5 dd, J=8Hz, 4Hz), 8.31 (1H, dd, J=8Hz, 1Hz), 8.61 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 77-(2) According to the same manner as that of Reference Preparation Example 13, 1-(3-chloro-2-pyridinyl)-3 10 methylsulfonyl-1H-pyrazole-5-carboxylic acid was used in place of 1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid to obtain 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3 methylsulfonyl-1H-pyrazol-5-yl)-8-methyl-4H-3,1-benzoxazine -4-one of the formula:

H

3 C '0 0 N %N 0 0 N ON N CI N . N 15

H

3 C 6-Chloro-2-[1-(3-chloro-2-pyridinyl)-3-methylsulfonyl-1H pyrazol-5-yl]-8-methyl- 4

H-

3 ,1-benzoxazine-4-one .583 , 1 H-NMR (CDCl3,TMS) 5 (ppm): 1.85 (3H, s), 3.30 (3H, s), 7.52-7.57 (2H, m), 7.72 (1H, s), 7.99-8.03 (2H, m), 8.58 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 78 5 To a mixture of 0..20 g of 6-chloro-2-[1-(3-chloro 2-pyridinyl)-3-methylthio-1H-pyrazol-5-yl]-8-methyl- 4

H-

3 ,1 benzoxazine-4-one, 5 ml of dichloromethane and 0.5 ml of water was added 0.18 g of magnesium bis(monoperoxophthalate) hexahydrate (MMPP), and the resulting mixture was stirred at 10 room temperature for 22 hours. Water was added to the reaction mixture, and the mixture was extracted with methyl t-butyl ether. The organic layer was washed with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to 15 obtain 0.20 g of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3 methylsulfinyl-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine -4-one of the formula:

H

3 C O 0 0 C, N C1 N

H

3 C 6-Chloro-2-[1-(3-chloro-2-pyridinyl)-3-methylsulfinyl-lH 20 pyrazol-5-yl)-8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.85 (3H, s), 3.04 (3H, s), .584 7.52-7.55 (2H, m), 7.74 (1H, s), 7.99-8.01 (2H, m), 8.58 (lH, dd, J=4Hz, 1Hz). Reference Preparation Example 79-(1) A mixture of 2.5 g of ethyl 2,4-dioxovalerate, 1.45 g of, 5 0-methylhydroxylamine hydrochloride and 10 ml of ethanol was heated to reflux for 2 hours. The reaction mixture was allowed to cool to room temperature, and partitioned between water and ethyl acetate. The organic layer was washed with water and an aqueous saturated sodium chloride solution, dried over 10 anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 1.34 g of ethyl 2-methoxyimino-4 oxopentanoate of the formula: 0

H

3 C

OCH

2

CH

3 0 NOCH 3 15 Ethyl 2-methoxyimino-4-oxopentanoate H-NMR (CDC1 3 ,TMS) 5 (ppm): 1.35 (3H, t, J=7Hz), 2.21 (3H, s), 3.71 (2H, s), 4.07 (3H, s), 4.34 (2H, q, J=7Hz). Reference Preparation Example 79-(2) A mixture of 1.34 g of ethyl 2-methoxyimino-4 20 oxopentanoate, 1.23 g of 3-chloro-2-hydrazinopyridine, 25 ml of tetrahydrofuran and 50 ml of acetic acid was heated to ref lux for 8 hours. The reaction mixture was concentrated under reduced pressure. Water was poured into the residue, and the ,585 mixture was extracted with methyl t-butyl ether two times. The combined organic layer was washed successively with a 1N aqueous sodium hydroxide solution, water and an aqueous saturated sodium chloride solution, dried over anhydrous 5 magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.30 g of ethyl 1-(3-chloro-2-pyridinyl)-3-methyl 1H-pyrazole-5-carboxylate of the formula:

H

3 C N,N CO 2

CH

2

CH

3 C1N 10 Ethyl 1- (3-chloro-2-pyridinyl) -3-methyl-lH-pyrazole-5 carboxylate 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.20 (3H, t, J=7Hz), 2.40 (3H, s), 4.20 (2H, q, J=7Hz), 6.84 (lH, s), 7.40 (lH, dd, J=8Hz, 4Hz), 7.88 (lH, d, J=8Hz), 8.51 (1H, d, J=4Hz). 15 Reference Preparation Example 79-(3) A mixture of 0.30 g of ethyl 1-(3-chloro-2-pyridinyl)-3 methyl-lH-pyrazole-5-carboxylate, 5 ml of methanol and 5 ml of a 2N aqueous sodium hydroxide solution was heated to reflux for 3 hours. After the reaction mixture was allowed to cool, water 20 was poured and the aqueous layer was washed with methyl t-butyl ether two times. The aqueous layer was adjusted to around pH 3 by an addition of 2N hydrochloric acid, and then extracted 586 with methyl t-butyl ether three times. The combined organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 0.24 g of 5 1-(3-chloro-2-pyridinyl)-3-methyl-lH-pyrazole-5-carboxylic acid of the formula:

H

3 C N'N CO 2 H 1-(3-Chloro-2-pyridinyl)-3-methyl-lH-pyrazole-5-carboxylic acid 10 1H-NMR (CDC1 3 ,TMS) 5 (ppm): 2.40 (3H, s), 6.89 (lH, s), 7.40 (1H, dd, J=8Hz, 4Hz), 7.89 (lH, dd, J=8Hz, lHz), 8.49 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 79-(4) According to the same manner as that of Reference 15 Preparation Example 13, 1-(3-chloro-2-pyridinyl)-3-methyl 1H-pyrazole-5-carboxylic acid was used in place of 1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid to obtain 6-chloro-2-[l-(3-chloro-2-pyridinyl)-3-methyl-1H pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine-4-one of the 20 formula: 587

H

3 C N, 0 0 N

H

3 C C , 6-Chloro-2-[1-(3-chloro-2-pyridinyl)-3-methyl-lH-pyrazol-5 yl]-8-methyl-4H-3,l-benzoxazine-4-one 'H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.81 (3H, s), 2.45 (3H, s), 7.07 5 (lH, s), 7.43-7.47 (2H, m), 7.92-7.98 (2H, m), 8.56 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 80-(1) To a mixture of 17.2 g of, 3-methyl-2-butanone, 27.1 g of diethyl oxalate and 130 ml of ethanol was added 95 ml of sodium 10 ethoxide (20% ethanol solution), and the resulting mixture was stirred at 60*C for 5 hours. After allowed to cool to room temperature, a deposited precipitate was collected by filtration and washed with ethanol. The filter cake was partitioned between 2N hydrochloric acid and methyl t-butyl 15 ether. The organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 28.8 g of ethyl 4-hydroxy-5-methyl-2-oxo-3-hexenoate of the formula: 588 0

(H

3

C)

2 HC r

OCH

2

CH

3 OH O Ethyl 4-hydroxy-5-methyl-2-oxo-3-hexenoate 1 H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.19 (6H, d, J=7Hz), 1.38 (3H, t, J=7Hz), 2.66 (lH, hept., J=7Hz), 4.36 (2H, q, J=7Hz), 6.41 (1H, 5 s). Reference Preparation Example 80-(2) A mixture of 5.0 g of ethyl 4-hydroxy-5-methyl-2-oxo-3-hexenoate, 2.46 g of O-methylhydroxylamine hydrochloride and 10 ml of ethanol was 10 stirred at room temperature for 6 hours. After ethyl acetate was poured into the reaction mixture, the organic layer was washed with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 5.32 g of ethyl 15 2-methoxyimino-5-methyl-4-oxohexanoate of the formula: 0

(H

3

C)

2 HC

OCH

2

CH

3 0 NOCH 3 Ethyl 2-methoxyimino-5-methyl-4-oxohexanoate 'H-NMR (CDCl 3 ,TMS) 8 (ppm): 1.15 (6H, d, J=7Hz), 1.34 (3H, t, J=7Hz), 2.68 (1H, hept., J=7Hz), 3.76 (2H, s), 4.05 (3H, s), 20 4.33 (2H, q, J=7Hz). Reference Preparation Example 80-(3) 589 A mixture of 3.0 g of ethyl 2-methoxyimino-5-methyl- 4 oxohexanoate, 2.4 g of 3-chloro-2-hydrazinopyridine, 50 ml of tetrahydrofuran and 100 ml of acetic acid was stirred at room temperature for 20 hours, and then heated to reflux for 4 hours.' 5 The reaction mixture was concentrated under reduced pressure. Water was poured into the residue, and the mixture was extracted with methyl t-butyl ether two times. The combined organic layer was washed successively with a 1N aqueous sodium hydroxide solution, water and an aqueous saturated chloride solution, 10 dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 1.07 g of ethyl 1-(3-chloro-2-pyridinyl)-3-isopropyl-1H-pyrazole-5-carboxyl ate of the formula:

(H

3

C)

2 HC N'N CO 2

CH

2

CH

3 Cl't 15 Ethyl 1- (3-chloro-2-pyridinyl) -3-isopropyl-1H-pyrazole-5 carboxylate 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.20 (3H, t, J=7Hz), 1.34 (6H, d, J=7Hz), 3.11 (1H, hept., J=7Hz), 4.20 (2H, q, J=7Hz), 6.88 (lH, 20 s), 7.40 (lH, dd, J=8Hz, 4Hz), 7.88 (1H, d, J=8Hz), 8.52 (1H, d, J=4Hz). Reference Preparation Example 80-(4) ,590 , A mixture of 1.07 g of ethyl 1-(3-chloro-2-pyridinyl)-3 isopropyl-1H-pyrazole-5-carboxylate, 15 ml of methanol and 15 ml of a 2N aqueous sodium hydroxide solution was heated to reflux for 1.5 hours. After the reaction mixture was allowed 5 to cool, water was poured and the mixture was washed with methyl t-butyl ether two times. The aqueous layer was adjusted to around pH 3 by an addition of 2N hydrochloric acid, and then extracted with methyl t-butyl ether three times. The combined organic layer was washed with an aqueous saturated sodium 10 chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 0.97 g of 1- (3-chloro-2-pyridinyl) -3-isopropyl-1H-pyrazole-5 carboxylic acid of the formula:

(H

3

C)

2 HC N'N C0 2 H 15 1- (3-Chloro-2-pyridinyl) -3-isopropyl-lH-pyrazole-5 carboxylic acid 1 H-NMR (CDC13 , TMS) 5 (ppm) : 1. 33 (6H, d, J=7Hz) , 3. 10 (iH, hept. , J=7Hz), 6.93 (1H, s), 7.39 (lH, dd, J=8Hz, 4Hz), 7.88 (1H, d, J=8Hz), 8.49 (lH, d, J=4Hz). 20 Reference Preparation Example 80-(5) According to the same manner as that of Reference Preparation Example 13, 1-(3-chloro-2-pyridinyl)-3- 591 isopropyl-lH-pyrazole-5-carboxylic acid was used in place of 1- (3-chloro-2-pyridinyl) -lH-pyrazole-5-carboxylic acid to obtain 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-isopropyl-lH pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine- 4 -one of the 5 formula:

(H

3

C)

2 HC N N

H

3 C C1 6-Chloro-2- [1- (3-chloro-2-pyridinyl) -3-isopropyl-lH-pyrazol -5-yl)-8-methyl-4H-3,1-benzoxazine-4-one 1H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.37 (6H, d, J=7Hz), 1.81 (3H, s), 10 3.15 (1H, hept., J=7Hz), 7.12 (1H, s), 7.45 (1H, dd, J=8Hz, 4Hz), 7.47 (1H, d, J=lHz), 7.93 (1H, dd, J=8Hz, 1Hz), 7.98 (1H, d, J=lHz), 8.56 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 81 According to the same manner as that of Reference 15 Preparation Example 46, 1-(3-chloro-2-pyridinyl)-3 isopropyl-lH-pyrazole-5-carboxylic acid was used in place of 3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxylic acid to obtain 2-[l-(3-chloro-2-pyridinyl)-3-isopropyl-lH pyrazol-5-yll-6,8-dibromo-4H-3,1-benzoxazine-4-one of the 20 formula: 592

(H

3

C)

2 HC N 0 0 N Br Br 2-[1-(3-Chloro-2-pyridinyl)-3-isopropyl-1H-pyrazol-5-yll-6, 8-dibromo-4H-3,1-benzoxazine-4-one 'H-NMR (CDCl 1 ,TMS) 5 (ppm): 1.35 (6H, d, J=7fHz), 3.16 (1H, hept., 5 J=7Hz), 7.16 (1H, s), 7.43 (lH, dd, J=8Hz, 4Hz), 7.94 (1H, dd, J=8Hz, 1Hz), 8.03 (1H, d, J=2Hz), 8.25 (1H, d, J=2Hz), 8.56 (1H, dd, J=4Hz, 1Hz). Reference Preparation Example 82-(l) A mixture of 23.6 g of pyruvic aldehyde dimethylacetal and 10 23.8 g of N,N-dimethylformamide dimethylacetal was stirred at 80*C for 4 hours while produced methanol was distilled off, to obtain 38.8 g (purity: about 80 %) of 4-dimethylamino-1,1 dimethoxy-3-butene-2-one of the formula: 0

(CH

3

O)

2 CH CH=CH-N(CH 3

)

2 15 4-Dimethylamino-1,1-dimethoxy-3-butene-2-one 1 H-NMR (CDCl 3 ,TMS) 5 (ppm): 2.87 (3H, s), 3.11 (3H, s), 3.41 (6H, s), 4.58 (1H, s), 5.35 (1H, d, J=12Hz), 7.74 (1H, d, J=12Hz). Reference Preparation Example 82-(2) 20 A mixture of 5 g of 4-dimethylamino-1,1-dimethoxy-3 butene-2-one, 1.7 ml of hydrazine monohydrate and 15 ml of 593 methanol was stirred for 8 hours under heat refluxing. The reaction mixture was concentrated under reduced pressure to obtain 4.07 g of 3-(dimethoxymethyl)-1H-pyrazole of the formula:

(CH

3 0) 2 CH N, N 5 H. 3- (Dimethoxymethyl) -1H-pyrazole 1 H-NMR (CDCl 3 ,TMS) 6 (ppm): 3.37 (6H, s), 5.58 (1H, s), 6.35 (1H, d, J=2Hz), 7.58 (1H, d, J=2Hz). Reference Preparation Example 82-(3) 10 According to the same manner as that of Reference Preparation Example 22, 3-(dimethoxymethyl)-lH-pyrazole was used in place of 3-bromo-1H-pyrazole to obtain 3-chloro-2-(3-(dimethoxymethyl)-1H-pyrazol-1-yl]pyridine of the formula:

(CH

3 0) 2 CH Nj N 15 3-Chloro-2-[3-(dimethoxymethyl)-1H-pyrazol-1-yl]pyridine 'H-NMR (CDClTMS) 5 (ppm): 3.44 (6H, s), 5.58 (1H, s), 6.57 (lH, d, J=2Hz), 7.29 (lH, dd, J=8Hz, 5Hz), 7.90 (lH, dd, J=8Hz, 2Hz), 8.07 (1H, d, 2Hz), 8.47 (lH, dd, 5Hz, 2Hz). 20 Reference Preparation Example 82-(4) .594 A mixture of 3.35 g of 3-chloro-2-[3-(dimethoxymethyl) 1H-pyrazol-1-yl]pyridine, 24 ml of formic acid and 6ml of water was stirred at 60*C for 1 hour. The reaction mixture was concentrated under reduced pressure. Ice water was poured into' 5 the residue, and a precipitated solid was collected by filtration to obtain 2.38 g of 1-(3-chloro-2-pyridinyl)-1H pyrazole-3-carbaldehyde of the formula: CHO N N 1-(3-Chloro-2-pyridinyl)-1H-pyrazole-3-carbaldehyde 10 'H-NMR (CDC1 3 ,TMS) 5 (ppm) : 7.01 (1H, d, J=2Hz) , 7.40 (1H, dd, J=8Hz, 5Hz), 7.98 (1H, dd, J=8Hz, 2Hz), 8.18 (1H, dd, J=3Hz, 2Hz), 8.52 (1H, dd, 5Hz, 2Hz), 10.14 (1H, d, 2Hz). Reference Preparation Example 82-(5) A mixture of 2.00 g of 1-(3-chloro-2-pyridinyl)-1H 15 pyrazole-3-carbaldehyde, 1.21 g of 0-methylhydroxylamine hydrochloride and 8 ml of pyridine was heated to reflux for 1 hour. After the reaction mixture was concentrated under reduced pressure, an aqueous saturated sodium hydrogen carbonate solution was poured into the residue and the mixture 20 was extracted with methyl t-butyl ether three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over .595 anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 2.23 g of 1-(3-chloro-2-pyridinyl)-1H pyrazole-3-carbaldehyde 0-methyloxime of the formula: H

CH

3 0N N, N 5 as a mixture of an E isomer and Z isomer (E isomer: Z isomer=3:1). 1- (3-Chloro-2-pyridinyl) -1H-pyrazole-3-carbaldehyde 0-methyloxime 1 H-NMR (CDCl 3 ,TMS) 5 (ppm): 10 E isomer: 3.99 (3H, s), 6.84 (1H, d, J=3Hz), 7.30 (1H, dd, J=8Hz, 5Hz), 7.92 (1H, dd, J=8Hz, 2Hz), 8.12 (1H, dd, J=3Hz, 1Hz), 8.25 (1H, s), 8.48 (1H, dd, J=5Hz, 2Hz). Z isomer: 4.07 (3H, s), 7.18 (1H, d, J=3Hz), 7.33 (1H, dd, J=BHz, 5Hz), 7.67 (1H, s), 7.93 (1H, dd, J=8Hz, 2Hz), 8.14 (1H, dd, 15 J=3Hz, 1Hz), 8.49 (1H, dd, J=5Hz, 2Hz). Reference Preparation Example 82-(6) According to the same manner as that of Reference Preparation Example 23, 1-(3-chloro-2-pyridinyl)-1H pyrazole-3-carbaldehyde 0-methyloxime was used in place of 20 2-(3-bromo-1H-pyrazol-1-yl)-3-chloropyridine to obtain 1- (3-chloro-2-pyridinyl) -3-methoxyiminomethyl-1H-pyrazole-5 ,596 -carboxylic acid of the formula: H

CH

3 0N N CO 2 H as a mixture of an E isomer and a Z isomer (E isomer: Z isomer=3:1). 5 1-(3-Chloro-2-pyridinyl)-3-methoxyiminomethyl-lH-pyrazole-5 -carboxylic acid 'H-NMR (CDC1,TMS) 6 (ppm): E isomer: 4.00 (3H, s), 7.39 (1H, s), 7.45 (1H, dd, J=8Hz, 5Hz), 7.92 (1H, dd, J=8Hz, 2Hz), 8.15 (1H, s), 8.51 (1H, dd, J=5Hz, 10 2Hz). Z isomer: 4.08 (3H, s), 7.38 (1H, s), 7.51 (1H, dd, J=8Hz, 5Hz), 7.60 (1H, s), 7.94 (1H, dd, J=8Hz, 2Hz), 8.51 (lH, dd, J=5Hz, 2Hz). Reference Preparation Example 82-(7) 15 A mixture of 0.70 g of 1-(3-chloro-2-pyridinyl)-3 methoxyiminomethyl-lH-pyrazole-5-carboxylic acid and 0.55 ml of thionyl chloride was heated to reflux for 1 hour. The reaction mixture was allowed to cool to room temperature, and then concentrated under reduced pressure. After the resulting 20 residue was dissolved in 10 ml of acetonitrile, 0.46 g of 2-amino-5-chloro-3-methylbenzoic acid was added and the ,597 mixture was stirred at room temperature for 10 minutes. To the mixture was added 0.35 ml of triethylamine, and the mixture was stirred at room temperature for 20 minutes. Further 70 ml of triethylamine was added, and the mixture was stirred at room' 5 temperature for 20 minutes. Then 0.21 ml of methanesulfonyl chloride was added, and the mixture was stirred at room temperature 'for 17 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform three times. The organic layers were combined, washed with an aqueous 10 saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.16 g of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3 cyano-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine-4-one of 15 the formula: NCN C0 N NN 71 N ci\

H

3 C 6-Chloro-2-[l-(3-chloro-2-pyridinyl)-3-cyano-1H-pyrazol-5 yl]-8-methyl-4H-3,1-benzoxazine-4-one 1 H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.83 (3H, s), 7.52 (1H, dd, J=2Hz, 20 1Hz), 7.56 (1H, dd, 8Hz, 5Hz), 7.58 (1H, s), 7.99-8.03 (2H, m), 8.58 (1H, dd, J=5Hz, 2Hz).

598 Reference Preparation Example 83 To a mixture of 10.6 ml of methylhydrazine, 50 ml of methanol and 8.0 g of sodium hydroxide was added dropwise 15.4 ml of methyl chloroformate under ice-cooling, and the mixture' 5 was stirred at room temperature for 1 hour. The reaction mixture was filtered, and the filtrate was concentrated. The residue was distilled under reduced pressure (50 to 80*C/15 mmHg) to obtain 13.4 g of N-methyl-N-methoxycarbonylhydrazine. N-methyl-N-methoxycarbonylhydrazine 10 1 H-NMR (CDCl 3 ,TMS) & (ppm): 3.11 (3H, s), 3.73 (3H, s), 4.13 (2H, brs). Reference Preparation Example 84 A mixture of 1.0 g of 2-[3-bromo-1-(3-chloro-2 pyridinyl)-lH-pyrazol-5-yl]-6-chloro-8-methyl- 4

H-

3 ,1 15 benzoxazine-4-one, 0.35 ml of methylhydrazine and 20 ml of tetrahydrofuran was stirred at room temperature for 24 hours. Water was poured into the reaction mixture and the mixture was extracted with ethyl acetate three times. The combined organic layer was washed with an aqueous saturated sodium chloride 20 solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.85 g of 3-bromo-N-[4-chloro-2-(N-methylhydrazinocarbonyl)-6 methylphenyl)-1-(3-chloro-2-pyridinyl)-lH-pyrazole-5 25 carboxamide of the formula: .599 Br H 3 C CI C1Bom- O N4clr--(-ehlhdaioabnl 6 N CH3 3-Bromo-N-[4-chloro-2-(N-methylhydrazinocarbonyl)-6 methylphenyl)-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5 carboxamide 5 1 H-NMR (CDCl 3 ,TMS) 6 (ppm): 2.20 (3H, s), 3.21 (3H, s), 3.74 (3H, brs), 7.05 (1H, s), 7.26-7.38 (3H, m), 7.86 (1H, dd, J=8Hz, 2Hz),,8.03 (1H, s), 8.42 (lH, dd, J=5Hz, 2Hz), 9.47 (lH, s). Reference Preparation Example 85-(1) To a mixture of 0.34 g of 2-amino-4-chloro-3 10 methylbenzoic acid and 10 ml of N,N-dimethylformamide was added 0.26 g of N-chlorosuccinimide at room temperature, and the mixture was stirred at room temperature for 5 hours. After 30 ml of water was poured into the reaction mixture, the mixture was extracted with ethyl acetate three times. The organic 15 layers were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 0.22 g of 2-amino-4,5-dichloro-3-methylbenzoic acid of the formula: HO 0

H

2 N ,

H

3 C C1 C1 600 2-Amino-4, 5-dichloro-3-methylbenzoic acid 'H-NMR (DMSO-d 6 ,TMS) 6 :2.25 (3H, s), 7.76 (1H, s). Reference Preparation Example 85-(2) According to the same manner as that of Reference 5 Preparation Example 46-(1), 2-amino-4,5-dichloro-3 methylbenzoic acid was used in place of 2-amino-3,5 dibromobenzoic acid to obtain 2-[3-bromo-1-(3-chloro-2 pyridinyl)-1H-pyrazol-5-yl]-6,7-dichloro-8-methyl- 4

H-

3 ,1 benzoxazine-4-one of the formula: Br N , 0 0 N

H

3 C 10 C . 2- [3-Bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl) -6,7 dichloro-8-methyl-4H-3,1-benzoxazine-4-one 1 H-NMR (DMSO-d 6 ,TMS) 5 :1.82 '(3H, s), 7.57 (1H, s), 7.77 (1H, dd, J=8Hz, 5Hz), 8.14 (1H, s), 8.36 (1H, d, J=8Hz), 8.64 (1H, 15 d, J=5Hz). Reference Preparation Example 86-(1) A mixture of 1. 0 g of 2-amino-5-iodo-3-methylbenzoic acid, 0. 45 g of copper cyanide and 10 ml of N,N-dimethylformamide was stirred at 150 0 C for 9 hours. The reaction mixture was 20 concentrated under reduced pressure. Into the residue, 20 ml of water and 2 ml of ethylenediamine were poured, and the .601 mixture was stirred at room temperature for 1 hour. After the reaction mixture was filtered, the filtrate was adjusted to around pH 5 by an addition of concentrated hydrochloric acid, and then extracted with ethyl acetate three times. The combined 5 organic layer was dried over sodium sulfate, and concentrated under reduced pressure to obtain 0.40 g of 2-amino-5-cyano-3-methylbenzoic acid of the formula: HO 0

H

2 N

H

3 C CN. 2-Amino-5-cyano-3-methylbenzoic acid 10 'H-NMR (DMSO-d 6 ,TMS) 6 :2.13 (3H, s), 7.34 (2H, brs), 7.51 (1H, d, J=2Hz), 7.'97 (1H, d, J=2Hz). Reference Preparation Example 86-(2) According to the same manner as that of Reference Preparation Example 46-(1), 2-amino-5-cyano-3-methylbenzoic 15 acid was used in place of 2-amino-3, 5-dibromobenzoic acid to obtain 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5 yl]-8-methyl-6-cyano-4H-3,1-benzoxazine-4-one of the formula: Br N, 0 0 N

H

3 C CN 20 2-[3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-8- .602 methyl-6-cyano-4H-3,1-benzoxazine-4-one 1 H-NMR (DMSO-d 6 ,TMS) 6 :1.73 (3H, s), 7.60 (1H, s), 7.77 (1H, dd, J=8Hz, 5Hz), 8.10 (1H, d, J=2Hz), 8.34-8.39,(2H, m), 8.63 (1H, d, J=5Hz). 5 Reference Preparation Example 87-(1) To a mixture of 15.1 g of N-methyl anthranilic acid and 300 ml acetic acid was added dropwise 3.2 g of bromine over 15 minutes. The resulting mixture was stirred at room temperature for 5 hours. Further 1.6 g of bromine was added dropwise thereto 10 over 15 minutes, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was filtered, and the resulting solid was washed successively with acetic acid, ethyl acetate and acetone to obtain 23 g of 3,5-dibromo-2-methylaminobenzoic acid of the formula: HO 0 H H3C'N 15 Br Br 3,5-Dibromo-2-methylaminobenzoic acid 'H-NMR (DMSO-d 6 ,TMS) 5 :2.89-2.92 (3H, m), 7.76-7.79 (1H, m), 7.83-7.86 (1H, m). Reference Preparation Example 87-(2) 20 A mixture of 1.0 g of 3-bromo-l-(3-chloro-2-pyridinyl) 1H-pyrazole-5-carboxylic acid, 2 ml of thionyl chloride and one drop of N,N-dimethylformamide was stirred at 80*C for 1 hour. After he reaction mixture was concentrated under reduced .603 pressure, 10 ml of hexane was added and the mixture was further concentrated under reduced pressure. The resulting residue was mixed with 20 ml of acetonitrile and 0.93 g of 3, 5-dibromo-2-methylaminobenzoic acid. After the mixture was 5 stirred at room temperature for 1 hour, 0.6 g of triethylamine was added and the mixture was further stirred at room temperature for 1 hour. The reaction mixture was poured into 30 ml of water, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed 10 successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was washed with methyl t-butyl ether to obtain 1.3 g of 3,5-dibromo 2-{N-[3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazole-5 15 carbonyl]-N-methylamino)benzoic acid of the formula: Br Br Br N CI)

HN

3

C

0 OH 3, 5-Dibromo-2-{N- [3-bromo-1- (3-chloro-2-pyridinyl) -lH pyrazole-5-carbonyl)-N-methylamino)benzoic acid 1 H-NMR (DMSO-d 6 ,TMS) 6 :2.98-3.34 (3H, m), 5.95 (1H, s), 7.62 20 (lH, dd, J=8Hz, 5Hz), 7.70 (1H, d, J=2Hz), 7.89 (1H, d, J=2Hz), 8.18 (1H, d, J=8Hz), 8.49 (1H, d, J=5Hz). Reference Preparation Example 88 ,604 To a mixture of 0.13 g of N,N'-dimethylhydrazine dihydrochloride, 1 ml of water, 0.14 g of potassium carbonate and 10 ml of tetrahydrofuran was added 0.23 g of 2- [3-bromo-1- (3-chloro-2-pyridinyl) -lH-pyrazol-5-yl] -6 5 chloro-8-methyl-4H-3,1-benzoxazine-4-one, and the resulting mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into 30 ml of water, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, dried over anhydrous sodium sulfate, and 10 concentrated under reduced pressure. The residue was washed with ethyl acetate to obtain 0.35 g of 3-bromo-N-[4-chloro 2- (N, N' -dimethylhydrazinocarbonyl) -6-methylphenyl] -1- (3 chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide of the formula: Br , H 3 C CI N N H N H N C1 0 N 'CH 3 N CH 3 15 3-Bromo-N-[4-chloro-2-(N,N'-dimethylhydrazinocarbonyl)-6 methylphenyl]-1-(3-chloro-2-pyridinyl) -lH-pyrazole-5 carboxamide 'H-NMR (DMSO-d 6 ,TMS) 6 :1.99-2.40 (6H, m), 2.98-3.09 (3H, m), 20 4.61 (0.7H, brs), 5.68 (0.3H, brs), 7.14-7.51 (3H, m), 7.61 (lH, dd, J=8Hz, 5Hz), 8.18 (1H, d, J=5Hz), 8.50 (1H, d, J=2Hz), 10.03 (0.6H, brs), 10.39 (0.4H, brs).

605 Reference Preparation Example 89-(l) To a mixture of 0.78 g of 2-amino-5-fluorobenzoic acid and 100 ml of N,N-dimethylformamide was added 1.1 g of N-bromosuccinimide at room temperature, and the mixture was 5 stirred at room temperature for 5 hours. After water was added to the reaction mixture, a deposited precipitate was collected by filtration, and then washed with acetone to obtain 0.43 g of 2-amino-3-bromo-5-fluorobenzoic acid of the formula: HO 0

H

2 N Br , F. 10 2-Amino-3-bromo-5-fluorobenzoic acid 1 H-NMR (DMSO-d 6 ,TMS) 6 :7.55 (1H, dd, J=8Hz, 3Hz), 7.71 (1H, dd, J=8Hz, 3Hz). Reference Preparation Example 89-(2) According to the same manner as that of Reference 15 Preparation Example 46-(1), 2-amino-3-bromo-5-fluorobenzoic acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 2-[3-bromo-l-(3-chloro-2-pyridinyl)-1H-pyrazol-5 yl]-8-bromo-6-fluoro-4H-3,1-benzoxazine-4-one of the formula: Br N OI C0 0 N 2B F 20 Br 606 2-[3-Bromo-1-(3-chloro-2-pyridinyl)-lH-pyrazol-5-yll-8 bromo-6-fluoro-4H-3,1-benzoxazine-4-one 1 H-NMR (DMSO-d 6 ,TMS) 6 :7.54 (lH, s), 7.72 (1H, dd, J=8Hz, 5Hz), 7.92 (1H, dd, J=8Hz, 3Hz), 8.15 (lH, dd, J=8Hz, 3Hz), 8.32 (lH,' 5 dd, J=8Hz, 1Hz), 8.59 (1H, dd, J=5Hz, 1Hz). Reference Preparation Example 90-(1) According to the same manner as that of Reference Preparation Example 63-(1), 2-phenylaniline was used in place of 3-chloro-2-methylaniline to obtain N-(biphenyl-2-yl)-2 10 (hydroxyimino)acetamide of the formula: H HO'N yN 01, N-(biphenyl-2-yl)-2-(hydroxyimino)acetamide 1 H-NMR (DMSO-d 6 ,TMS) 6 :7.27-7.48 (9H, m), 7.83 (lH, d, J=8Hz), 9.18 (1H, s), 12.14 (lH, s). 15 Reference Preparation Example 90-(2) According to the same manner as that of Reference Preparation Example 63-(2), N-(biphenyl-2-yl)-2 (hydroxyimino)acetamide was used in place of N-(3-chloro-2-methylphenyl)-2-(hydroxyimino)acetamide to 20 obtain 7-phenyl-1H-indole-2,3-dione of the formula: .607 0 O HN 7-Phenyl-lH-indole-2,3-dione 'H-NMR (DMSO-d 6 ,TMS) 6 :7.18 (1H, t, J=8Hz), 7.40-7.63 (7H, m), 10.91 (1H, s). 5 Reference Preparation Example 90-(3) According to the same manner as that of Reference Preparation Example 63- (3), 7-phenyl-1H-indole-2, 3-dione was used ,in place of 6-chloro-7-methyl-1H-indole-2,3-dione to obtain 2-amino-3-phenylbenzoic acid of the formula: HO 0

H

2 N 10 2-Amino-3-phenylbenzoic acid 'H-NMR (DMSO-d 6 ,TMS) 6 :6.65 (1H, t, J=8Hz), 7.17 (lH, d, J=7Hz), 7.35-7.55 (5H, m), 7.78 (1H, d, J=BHz). Reference Preparation Example 90-(4) 15 According to the same manner as that of Reference Preparation Example 46-(1), 2-amino-3-phenylbenzoic acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-8 phenyl-4H-3,1-benzoxazine-4-one of the formula: ,608 Br 0 N 0 N <N 2-[3-Bromo-l-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-8 phenyl-4H-3,1-benzoxazine-4-one 1 H-NMR (DMSO-d 6 ,TMS) 5 :7.05-7.48 (7H, m), 7.61-7.89 (3H, m), 5 8.09-8.28 (2H, m). Reference Preparation Example 91 ,According to the same manner as that of Reference Preparation Example 71-(5), 2-amino-3,5-dibromobenzoic acid was used in place of 2-amino-5-chloro-3-methylbenzoic acid to 10 obtain 6,8-dibromo-2-[4-bromo-1-(3-chloro-2-pyridinyl)-lH pyrrol-2-yl]-4H-3,1-benzoxazine-4-one of the formula: Br 00 N/ N Br Br 6, 8-Dibromo-2-[4-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrrol-2 -yl]-4H-3,1-benzoxazine-4-one 15 1H-NMR (CDCl 3 ,TMS) 6 (ppm): 7.11 (1H, d, J=2Hz), 7.37 (1H, d, J=2Hz), 7.41 (1H, dd, J=8Hz, 5Hz), 7.92 (1H, dd, J=BHz, 2Hz), 7.97 (1H, d, J=2Hz), 8.20 (1H, d, J=2Hz), 8.51 (1H, dd, J=5Hz, 2Hz).

,609 Reference Preparation Example 92 According to the same manner as that of Reference Preparation Example 71-(5), 2-amino-3-bromo-5-chlorobenzoic acid was used in place of 2-amino-5-chloro-3-methylbenzoic 5 acid to obtain 8-bromo-2-[4-bromo-1-(3-chloro-2-pyridinyl) 1H-pyrrol-2-yl]-6-chloro-4H-3, 1-benzoxazine-4-one of the formula: Br 0 0 N Br CI 8-Bromo-2- [4-bromo-1- (3-chloro-2-pyridinyl)-1H-pyrrol-2-yl] 10 -6-chloro-4H-3,1-benzoxazine-4-one 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 7.11 (1H, d, J=2Hz), 7.37 (1H, d, J=2Hz), 7.41 (1H, dd, J=8Hz, 5Hz), 7.82 (1H, d, J=2Hz), 7.92 (1H, dd, J=8Hz, 2Hz), 8.05 (1H, d, J=2Hz), 8.51 (1H, dd, J=5Hz, 2Hz). 15 Reference Preparation Example 93 According to the same manner as that of Reference Preparation Example 71-(5), 2-amino-5-cyano-3-methylbenzoic acid was used in place of 2-amino-5-chloro-3-methylbenzoic acid to obtain 2-[4-bromo-1-(3-chloro-2-pyridinyl)-lH 20 pyrrol-2-yl]-6-cyano-8-methyl- 4

H-

3 ,1-benzoxazine-4-one of the formula: .610 Br 0 0 N me CN 2- [4-Bromo-1- (3-chloro-2-pyridinyl) -1H-pyrrol-2-yl] -6-cyano -8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (DMSO-d 6 ,TMS) 6 (ppm): 1.68 (3H, s), 7.35 (lH, d, J=2Hz), 5 7.67 (1H, dd, J=8Hz, 5Hz), 7.70 (1H, d, J=2Hz), 7.97 (1H, s), 8.23 (1H, dd, J=8Hz, 2Hz), 8.28 (1H, s), 8.57 (1H, dd, J=5Hz, 2Hz). Reference Preparation Example 94-(1) According to the same manner as that of Reference 10 Preparation Example 63-(1), 2-ethylaniline was used in place of 3-chloro-2-methylaniline to obtain N-(2-ethylphenyl)-2 (hydroxyimino)acetamide of the formula: H HO' N N H3C2 N-(2-ethylphenyl)-2-(hydroxyimino)acetamide 15 1 H-NMR(DMSO-d 6 ,TMS)6:1.12(3H,t,J=8Hz),2.59(2H,q,J=8Hz),7.15 -7.27(3H,m),7.43(lH,dd,J=6Hz,4Hz),7.67(lH,s),9.49(1H,s),12. 17(lH,s). Reference Preparation Example 94-(2) 20 According to the same manner as that of Reference ,611 Preparation Example 63-(2), N-(2-ethylphenyl)-2 (hydroxyimino)acetamide was used in place of N-(3-chloro-2 methylphenyl) -2- (hydroxyimino) acetamide to obtain crude 7-ethyl-lH-indole-2,3-dione of the formula: 0 O HN 5 H 3

CH

2 C Reference Preparation Example 94-(3) A mixture of 1.0 g of crude 7-ethyl-1H-indole-2,3-dione and 3 ml of a 2N aqueous sodium hydroxide solution was added dropyise to 2 g of aqueous hydrogen peroxide (30%) at room 10 temperature, and the resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was adjusted to pH 4 by an addition of 2N hydrochloric acid, and a deposited precipitate was collected by filtration. The resulting filter cake was partitioned between ethyl acetate and a saturated 15 sodium hydrogen carbonate solution. The aqueous layer was adjusted to pH 4 by an addition of 2N hydrochloric acid, and a deposited precipitate was collected by filtration to obtain 0.42 g of 2-amino-3-ethylbenzoic acid of the formula: HO O H2N j

H

3

CH

2 C 20 2-Amino-3-ethylbenzoic acid 1 H-NMR (DMSO-d 6 ,TMS) 5 :1.15 (3H, t, J=7Hz), 2.44-2.53 (2H, m), 612 6.50 (1H, dd, J=8Hz, 7Hz), 7.15 (1H, d, J=7Hz), 7.62 (1H, d, J=8Hz). Reference Preparation Example 94-(4) According to the same manner as that of Reference 5 Preparation Example 46-(1), 2-amino-3-ethylbenzoic acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl)-8 ethyl-4H-3,1-benzoxazine-4-one of the formula: Br N, yoO C N N

CH

2

CH

3 10 2-[3-Bromo-1- (3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-8 ethyl-4H-3,1-benzoxazine-4-one 1 H-NMR (DMSO-d 6 ,TMS) 6 :0.81 (3H, t, J=7Hz), 2.07 (2H, q, J=7Hz), 7.47-7.57 (2H, m), 7.70 (1H, d, J=7Hz), 7.79 (1H, dd, J=8,5Hz), 7.95 (1H, d, J=7Hz) , 8.37 (1H, d, J=8Hz), 8.64 (1H, d, J=5Hz) . 15 Reference Preparation Example 95-(l) According to the same manner as that of Reference Preparation Example 67- (1), cyclohexylhydrazine hydrochloride was used in place of tert-butylhydrazine hydrochloride to obtain 1-cyclohexyl-3-trifluoromethyl-1H-pyrazole of the 20 formula: .613

F

3 C N N 1-Cyclohexyl-3-trifluoromethyl-lH-pyrazole 'H-NMR (CDCl 3 ,TMS) 6 (ppm): 1.19-1.33 (3H, m), 1.67-1.77 (2H, m), 1.93-1.99 (4H, m), 2.16-2.19 (1H, m), 4.13-4.20 (1H, m), 5 6.49 (lH, s), 7.45 (1H, s) . Reference Preparation Example 95-(2) According to the same manner as that of Reference Preparation Example 15, 1-cyclohexyl-3-trifluoromethyl-1H-pyrazole was used in place 10 of 3-chloro-2-(3-trifluoromethyl-1H-pyrazole-1-yl)pyridine to obtain 1-cyclohexyl-3-trifluoromethyl-1H-pyrazole-5 carboxylic acid of the formula:

F

3 C 'N CO 2 H 1-Cyclohexyl-3-trifluoromethyl-lH-pyrazole-5-carboxylic 15 acid 'H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.26-2.00 (10H, m), 5.10-5.18 (1H, m), 7.15 (1H, s). Reference Preparation Example 95-(3) According to the same manner as that of Reference ,614 Preparation Example 13, 1-cyclohexyl-3-trifluoromethyl-lH pyrazole-5-carboxylic acid was used in place of 1-(3-chloro 2-pyridinyl) -lH-pyrazole-5-carboxylic acid to obtain 6-chloro-2-(l-cyclohexyl-3-trifluoromethyl-lH-pyrazol-5-yl)' 5 -8-methyl-4H-3,1-benzoxazine-4-one of the formula:

F

3 C 0 0 N 3C CI 6-Ch.oro-2-(1-cyclohexyl-3-trifluoromethyl-1H-pyrazol-5-yl )-8-methyl-4H-3,1-benzoxazine-4-one 1 H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.26-1.54 (4H, m), 1.77 (1H, d, 10 J=2Hz), 1.96-2.62 (5H, m), 2.62 (3H, s), 5.51-5.58 (1H, m), 7.31 (1H, s), 7.69 (1H, d, J=2Hz), 8.07 (1H, d, J=2Hz). Reference Preparation Example 95-(4) According to the same manner as that of Reference Preparation Example 1, 6-chloro-2-(l-cyclohexyl-3 15 trifluoromethyl-1H-pyrazol-5-yl)-8-methyl- 4

H-

3 ,1 benzoxazine-4-one was used in place of 6-chloro-2-[l-(3 chloro-2-pyridinyl)-3-trifluoromethyl-1H-pyrazol-5-yl]-8 methyl-4H-3,1-benzoxazine-4-one to obtain N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl)-l-cyclohexyl-3 20 trifluoromethyl-H-pyrazole-5-carboxamide of the formula: 615 H3C CI

F

3 C 0 3 c FaCN N %N H Y ,NH2 0 N H N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl]-1 cyclohexyl-3-trifluoromethyl-lH-pyrazole-5-carboxamide 'H-NMR (DMSO-d 6 ,TMS) 8 (ppm): 1.20-1.39 (3H, m), 1.66 (1H, d, 5 J=12Hz), 1.75-1.84 (4H, m), 1.98 (2H, d, J=10Hz), 2.25 (3H, s), 4.36 (2H, brs), 5.03-5.09 (1H, m), 7.35 (2H, s), 7.52 (1H, s), 9.62 ,(1H, brs), 10.17 (1H, brs). Reference Preparation Example 96-(1) To a solution of 1.0 g of 3-chloro-2-(2-formyl-1H 10 pyrrol-1-yl)pyridine in 15 ml of N,N-dimethylformamide, 1.9 g of N-bromosuccinimide was added. The mixture was stirred at room temperature for 3 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed 15 with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 1.2 g of 4,5-dibromo-1-(3-chloro-2 pyridinyl)-lH-pyrrole-2-carbaldehyde of the formula: 616 Br Br N CHO CI N 4,5-Dibromo-l-(3-chloro-2-pyridinyl)-lH-pyrrole-2 carbaldehyde 'H-NMR (CDCl 3 ,TMS) 5 (ppm): 7.14 (1H, s), 7.47 (1H, dd, J=8Hz, 5 5Hz), 7.93 (1H, dd, J=8Hz, 2Hz), 8.53 (1H, dd, J=5Hz, 2Hz), 9.33 (1H, s). Reference Preparation Example 96-(2) To a mixture of 1.0 g of 4,5-dibromo-1-(3-chloro-2 pyridinyl)-1H-pyrrole-2-carbaldehyde, 15 ml of acetone and 7 10 ml of water was slowly added 1.3 g of potassium permanganate at 40 0 C. The resulting mixture was stirred at 60*C for 2 hours. Precipitates in the reaction mixture were removed by filtration. The resulting filtrate was washed with chloroform two times. The aqueous layer was adjusted to around pH 3 by an addition 15 of 2N hydrochloric acid and then extracted with ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain 0.69 g of 4,5-dibromo-1-(3-chloro 20 2-pyridinyl)-lH-pyrrole-2-carboxylic acid of the formula: 617 Br Br N CO 2 H CI N 4, 5-Dibromo-1- (3-chloro-2-pyridinyl) -1H-pyrrole-2 carboxylic acid H-NMR (DMSO-d 6 , TMS) 6 (ppm) : 7. 15 (1H, m) , 7. 64 (1H, dd, J=8Hz, 5 5Hz), 8.19 (1H, dd, J=8Hz, 2Hz), 8.56 (1H, dd, J=5Hz, 2Hz). Reference Preparation Example 96-(3) According to the same manner as that of Reference Preparation Example 71-(5), 4,5-dibromo-1-(3-chloro-2 pyridinyl) -lH-pyrrole-2-carboxylic acid was used in place of 10 4-bromo-1-(3-chloro-2-pyridinyl)-lH-pyrrole-2-carboxylic acid to obtain 2-[4,5-dibromo-1-(3-chloro-2-pyridinyl)-lH pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1-benzoxazine-4-one of the formula: Br Br N O C1 N N

H

3 C C. 15 2-[4,5-Dibromo--(3-chloro-2-pyridinyl)-1H-pyrrol-2-yl]-6 chloro-8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR (CDCl 3 ,TMS) 5 (ppm): 1.72 (3H, s), 7.40 (2H, s), 7.48 (1H, dd, J=8Hz, 5Hz), 7.92 (1H, s), 7.98 (1H, dd, J=8Hz, 2Hz), 8.58 (1H, dd, J=5Hz, 2Hz).

, 618, Reference Preparation Example 96-(4) According to the same manner as that of Reference Preparation Example 71-(6), 2-[4,5-dibromo-1-(3-chloro- 2 pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1 5 benzoxazine-4-one was used in place of 2-[4-bromo-1- (3-chloro 2-pyridinyl) -1H-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one to obtain 4,5-dibromo-N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl) -1- (3-chloro-2-pyridinyl )-1H-pyrrole-2-carboxamide of the formula:

H

3 C C1 Br N Br N H

NH

2 C1 O N N H 10 4,5-Dibromo-N-[4-chloro-2-(hydrazinocarbonyl)-6 methylphenyl] -1- (3-chloro-2-pyridinyl) -1H-pyrrole-2 carboxamide 'H-NMR (CDCl,,TMS) 8 (ppm): 2.15 (3H, s), 4.03 (2H, brs), 7.15 15 (lH, s), 7.22 (1H, d, J=3Hz), 7.25 (1H, d, J=3Hz), 7.37 (1H, dd, J=8Hz, 5Hz), 7.70 (1H, brs), 7.86 (1H, dd, J=8Hz, 2Hz), 8.47 (1H, dd, J=5Hz, 2Hz), 9.50 (1H, brs). Reference Preparation Example 97-(1) To a solution of 1.0 g of 3-chloro-2-(2-formyl-1H-pyrrol 20 1-yl) pyridine in 15 ml of N, N-dimethylformamide was added 0. 68 g of N-chlorosuccinimide. The resulting mixture was stirred ,619 at 50*C for 2 days. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over 5 anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.35 g of 4-chloro-1-(3-chloro-2 pyridinyl)-1H-pyrrole-2-carbaldehyde of the formula: C1 N CHO CIN 10 and 0.31 g of 5-chloro-l-(3-chloro-2-pyridinyl)-1H-pyrrole 2-carbaldehyde of the formula: CI N CHO CI N 4-Chloro-1-(3-chloro-2-pyridinyl)-lH-pyrrole-2-carbaldehyde 1

H-NMR(CDC

3 1 ,TMS)6(ppm):7.04(lH,d,J=2Hz),7.10(1H,dd,J=2Hz, 15 lHz),7.41(1H,dd,J=8Hz,5Hz),7.89(lH,dd,J=8Hz,2Hz),8.46(lH,dd, J=5Hz,2Hz),9.50(lH,d,J=lHz) 5-Chloro-l-(3-chloro-2-pyridinyl)-lH-pyrrole-2-carbaldehyde 'H-NMR(CDCl 3 ,TMS)5(ppm):6.41(lH,d,J=4Hz),7.08(1H,d,J=4Hz), 1 620 7.45(1H,dd,J=8Hz,5Hz),7.92(lH,dd,J=8Hz,2Hz),8.54(1H,dd, J=5Hz,2Hz),9.41(1H,s) Reference Preparation Example 97-(2) According to the same manner as that of Reference 5 Preparation Example 71-(4), 5-chloro-1-(3-chloro-2 pyridinyl)-1H-pyrrole-2-carbaldehyde was used in place of 4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carbaldehyde to obtain 5-chloro-l-(3-chloro-2-pyridinyl)-1H-pyrrole-2 carboxylic acid of the formula: CI N

CO

2 H 10 5-Chloro-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxylic acid 'H-NMR(DMSO-d 6 ,TMS)6(ppm):6.39(lH,d,J=4Hz),7.01(lH,d,J=4Hz), 7.62(1H,dd,J=8Hz,5Hz),8.13(1H,d,J=8Hz),8.54(1H,d,J=5Hz) 15 Reference Preparation Example 97-(3) According to the same manner as that of Reference Preparation Example 71-(5), 5-chloro-1-(3-chloro-2 pyridinyl)-1H-pyrrole-2-carboxylic acid was used in place of 4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2- carboxylic 20 acid to obtain 2-[5-chloro-1-(3-chloro-2-pyridinyl)-1H pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1-benzoxazine-4-one of the formula: .621 CI N C1 N / H3C CI 2-[5-Chloro-l-(3-chloro-2-pyridinyl)-1H-pyrrol-2-yl)-6 chloro-8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR(CDCl 3 ,TMS) 6(ppm):1.71(3H,s),6.43(lH,d,J=4Hz), 7

.

32 5 (lH,d,J=4Hz),7.38(1H,d,J=2Hz),7.47(1H,dd,J=8Hz,5Hz),7.92 (1H,d,J=2Hz),7.97(lH,dd,J=8Hz,2Hz),8.59(lH,dd,J=5Hz,2Hz) Reference Preparation Example 98-(l) According to the same manner as that of Reference Preparation Example 71-(4), 1-(3-chloro-2-pyridinyl)-lH 10 pyrrole-2-carbaldehyde was used in place of 4-bromo-1-(3 chloro-2-pyridinyl)-1H-pyrrole-2-carbaldehyde to obtain 1-(3-chloro-2-pyridinyl)-lH-pyrrole-2-carboxylic acid of the formula: N C0 2 H ClN 15 1-(3-Chloro-2-pyridinyl)-1H-pyrrole-2-carboxylic acid 'H-NMR(DMSO-C6,TMS)6(ppm):6.33-6.34(1H,m),6.97(lH,d,J= 4 Hz), 7.18(1H,brs),7.54(1H,dd,J=8Hz,5Hz),8.10(lH,d,J=8Hz),8.4 7 -8. 49(1H,m) Reference Preparation Example 98-(2) 622 According to the same manner as that of Reference Preparation Example 71-(5), 1-(3-chloro-2-pyridinyl) 1H-pyrrole-2-carboxylic acid was used in place of 4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxylic 5 acid to obtain 2-[1-(3-chloro-2-pyridinyl)-1H-pyrrol-2-yl) 6-chloro-8-methyl-4H-3,1-benzoxazine-4-one of the formula: 0 0 N

H

3 C C1 2-[1-(3-Chloro-2-pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8 methyl-4H-3,1-benzoxazine-4-one 10 'H-NMR(CDCl 3 ,TMS)5(ppm):1.73(3H,s),6.50(1H,dd,J=4Hz,3Hz), 7.09(1H,dd,J=3Hz,2Hz),7.36(lH,dd,J=4Hz,2Hz),7.39(lH,s),7.41 (1H,dd,J=8Hz,5Hz),7.90(1H,dd,J=8Hz,2Hz),7.93(lH,s),8.52(lH, dd,J=5Hz,2Hz) Reference Preparation Example 98-(3) 15 According to the same manner as that of Reference Preparation Example 71-(6), 2-[l-(3-chloro-2 pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8-methyl-4H- 3 ,1 benzoxazine-4-one was used in place of 2-[4-bromo-1 (3-chloro-2-pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8-methyl 20 4H-3,1-benzoxazine-4-one to obtain N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl)-1-(3-chloro-2 pyridinyl)-1H-pyrrole-2-carboxamide of the formula: 623

H

3 C Cl 0 N N HH HN2 N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl) -1- (3 chloro-2-pyridinyl)-1H-pyrrole-2-carboxamide H-NMR(DMSO-d,TMS)(ppm):2.16(3H,s),4.40(2H,brs),6.

37 (lH, 5 dd,J=4Hz,3Hz),7.13-7.16(2H,m),7.31(lH,d,J=2Hz),7.41(lH,brs), 7.47(lH,dd,J=8Hz,5Hz),8.02(lH,d,J=8Hz),8.42(lH,d,J=5Hz), 9.56(lH,brs),9.84(lH,brs) Reference Preparation Example 99 According to the same manner as that of Reference 10 Preparation Example 1, 2-[3-bromo-l-(3-chloro-2-pyridinyl) 1H-pyrazol-5-yl)-6-cyano-8-methyl-4H-3,1- benzoxazine-4-one was used in place of 6-chloro-2-[l-(3-chloro-2-pyridinyl)-3 trifluoromethyl-lH-pyrazol-5-yl)-8-methyl-4H-3,1 benzoxazine-4-one to obtain 3-bromo-l-(3-chloro-2-pyridinyl) 15 -N-[4-cyano-2-(hydrazinocarbonyl)-6-methylphenyl]-1H pyrazole-5-carboxamide of the formula:

H

3 C CN Br 0 NN N 'N H N 0 NH2 N H 3-Bromo-1-(3-chloro-2-pyridinyl)-N-[4-cyano-2- .624 (hydrazinocarbonyl) -6-methylphenyl] -1H-pyrazole-5 carboxamide 'H-NMR(DMSO-d)6:2.19(3H,s),4.41(2H,brs),7.41(lH,s),7.61(1H, dd,J=8Hz,5Hz),7.72(lH,s),7.88(1H,s),8.17(lH,d,J=8Hz), 5 8.50(1H,d,J=5Hz),9.65(1H,brs),10.52(1H,brs) Reference Preparation Example 100-(1) To a solution of 3.0 g of 3-chloro-2-(2-formyl-1H-pyrrol 1-yl)pyridine in 10 ml of N,N-dimethylformamide was added 4.5 g of N-chlorosuccinimide. The resulting mixture was stirred 10 at 50 0 C for 2 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate two times. The organic layers were combined,.washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced 15 pressure to obtain 3.6 g of 4,5-dichloro-l-(3-chloro-2 pyridinyl)-1H-pyrrole-2-carbaldehyde of the formula: CI Ci N CHO CI N 4,5-Dichloro-1-(3-chloro-2-pyridinyl)-lH-pyrrole-2 carbaldehyde 20 'H-NMR(CDCl 3 ,TMS)5(ppm):7.06(1H,s),7.47(lH,dd,J=8Hz,5Hz), 7.93(lH,dd,J=8Hz,2Hz),8.53(lH,dd,J=5Hz,2Hz),9.3 7 (lH,s) Reference Preparation Example 100-(2) 625 According to the same manner as that of Reference Preparation Example 71-(4), 4,5-dichloro-1-(3-chloro-2 pyridinyl)-lH-pyrrole-2-carbaldehyde was used in place of 4-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrrole-2- carbaldehyde' 5 to obtain 4, 5-dichloro-l- (3-chloro-2-pyridinyl) -1H-pyrrole 2-carboxylic acid of the formula: C1 Cl N CO 2 H C' N 4, 5-D'ichloro-l-(3-chloro-2-pyridinyl)-lH-pyrrole-2 carboxylic acid 10 1 H-NMR(DMSO-d 6 ,TMS)5(ppm):7.18(lH,s),7.68(1H,dd,J=8Hz,5Hz), 8.25(lH,dd,J=8Hz,2Hz),8.59(lH,dd,J=5Hz,2Hz) Reference Preparation Example 100-(3) According to the same manner as that of Reference Preparation Example 71-(5), 4,5-dichloro-l-(3-chloro-2 15 pyridinyl)-1H-pyrrole-2-carboxylic acid was used in place of 4 -bromo-l- (3-chloro-2-pyridinyl) -1H-pyrrole-2-carboxylic acid to obtain 2-[4,5-dichloro-l-(3-chloro-2-pyridinyl) 1H-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1-benzoxazine-4-one of the formula: .626 C1 CI N SN H 3 C CI 2-[4,5-Dichloro-1-(3-chloro-2-pyridinyl)-1H-pyrrol- 2 -yll 6-chloro-8-methyl-4H-3,1-benzoxazine-4-one H-NMR(CDCl3,TMS)6(ppm):1.71(3H,s),7.31(lH,s),7.40(lH,s), 5 7.49(lH,dd,J=8Hz,5Hz),7.92(lH,s),7.98(lH,d,J-8Hz), 8.58 (1H, d, J=5Hz) Reference Preparation Example 100-(4) According to the same manner as that of Reference Preparation Example 71-(6), 2-[4,5-dichloro-1-(3-chloro-2 10 pyridinyl)-H-pyrrole-2-yl-6-chloro-8-methyl- 4 H-3,1 benzoxazine-4-one was used in place of 2- [4-bromo-l- (3-chloro 2-pyridinyl)-lH-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one to obtain 4,5-dichloro-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyridinyl 15 )-1H-pyrrole-2-carboxamide of the formula: C1 H3C C1 N Cl H -- ,NH2 C1 O N -; N H 4,5-Dichloro-N-[4-chloro-2-(hydrazinocarbonyl)-6 methylphenyl)-1-(3-chloro-2-pyridinyl)-lH-pyrrole-2- 627 carboxamide 1H-NMR(CDCl 3 ,TMS)5(ppm):2.01(3H,s),4.03(2H,brs), 7 .0 7 (lH,s), 7.16(lH,d,J=2Hz),7.22(1H,d,J=2Hz),7.37(1H,dd,J=8Hz,5Hz), 7.47(1H,brs),7.86(1H,dd,J=8Hz,2Hz),8.47(lH,dd,J=5Hz, 2 Hz), 5 9.41(1H,brs) ' Reference Preparation Example 101 A mixture of 0.86 g of 2-[4-bromo-1-(3-chloro-2 pyridinyl)-lH-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one, 0.11 g of methylhydrazine and 15 ml of 10 tetrahydrofuran was stirred at room temperature for 2 hours. Waterwas poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to 15 silica gel chromatography to obtain 0.17 g of 4-bromo-N [4-chloro-2- (N-methylhydrazinocarbonyl) -6-methylphenylJ -1 (3-chloro-2-pyridinyl) -1H-pyrrole-2-carboxamide of the formula:

H

3 C CI Br O N N H NH2 C N 0 N

H

3 C 20 4-Bromo-N-[4-chloro-2-(N-methylhydrazinocarbonyl)-6 methylphenyl) -1- (3-chloro-2-pyridinyl) -1H-pyrrole-2 carboxamide - 628

H-NMR(CDC

3 ,TMS)5(ppm):2.14-2.16(3H,m),3.02- 3

.

2 3

(

3 Hm), 4.04(0.7H,brs),4.60(1.3H,brs),7.03(2H,s),7.11(0.5H,s), 7.19(0.5H,s),7.31(lH,dd,J=8Hz,4Hz),7.80(1H,d,J=8Hz), 8.41(1H,d,J=4Hz),8.56(1H,brs) 5 Reference Preparation Example 102 According to the same manner as that of Reference Preparation Example 46-(1), 2-amino-3,5-dichlorobenzoic acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 2- (3-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrazol-5-yl]-6,8 10 dichloro-4H-3,1-benzoxazine-4-one of the formula: Br 1 N 0 0 N C1 N C1 CI. 2-[3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-6,8 dichloro-4H-3,1-benzoxazine-4-one 1H-NMR(DMSO-d 6 ,TMS)5(ppm):7.57(lH,s),7.73(1H,dd,J=BHz,5Hz), 15 8.03(1H,d,J=2Hz),8.12(1H,d,J=2Hz),8.32(1H,dd,J=8Hz, 2 Hz), 8.60 (1H,dd,J=5Hz,2Hz) Reference Preparation Example 103 According to the same manner as that of Reference Preparation Example 84, 2-[3-bromo-l-(3-chloro-2 20 pyridinyl)-H-pyrazol-5-yl)-6-cyano-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 2- [3-bromo-1- (3-chloro 2-pyridinyl)-1H-pyrazol-5-yl]-6-chloro-8-methyl-4H-3,1- .629 benzoxazine-4-one to obtain 3-bromo-l-(3-chloro-2 pyridinyl)-N-[4-cyano-2-(N-methylhydrazinocarbonyl)-6 methylphenyl)-lH-pyrazole-5-carboxamide of the formula: Br

H

3 C CN 0 N H Ci 0 CI N NN H 3 C 5 3-Bromo-1-(3-chloro-2-pyridinyl)-N-{4-cyano-2-(N methylhydrazinocarbonyl)-6-methylphenyl]-1H-pyrazole-5 carboxamide H-NMR(DMSO-d 6 ,TMS)5(ppm):2.22(3H,s),2.75-3.10( 3 H,m), 4.51-5.03(2H,m),7.36(H,s),7.,60-7.71(2H,m),7.74-7.88(lH,m), 10 8.20(1H,d,J=8Hz),8.51(lH,d,J=4Hz),10.27-10.63(1H,m) Reference Preparation Example 104 According to the same manner as that of Reference Preparation Example 101, 2-[4-bromo-l-(3-chloro-2 yridinyl)-1H-pyrrol-2-yl)-6-cyano-8-methyl- 4

H-

3 ,1 15 enzoxazine-4-one was used in place of 2-[4-bromo-1-(3-chloro 2-pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8-methyl-4H- 3

,

1 benzoxazine-4-one to obtain 4-bromo-l-(3-chloro-2 pyridinyl)-N-[4-cyano-2-(N-methylhydrazinocarbonyl)-6 methylphenyl]-lH-pyrrole-2-carboxamide of the formula: .630 Br

H

3 C CN 0 / N N H NH2 CI N O N

H

3 C 4-Bromo-1- (3-chloro-2-pyridinyl) -N- [4-cyano-2- (N methylhydrazinocarbonyl)-6-methylphenyl]-1H-pyrrole-2 carboxamide 5 1 H-NMR(DMSO-d 6 ,TMS)6(ppm):2.21(3H,s),2.74- 3 .10 ( 3 H,m), 4 .51 4.99(2H,m),7.22-7.28,(lH,m),7.46-7.56(2H,m),7.56- 7 .65(1H,m), 7.70-7.84 (1H,m),8.09(1H, d, J=8Hz),8.44 (1H,d, J=4Hz), 9.76 10.04,(1H,m) Reference Preparation Example 105-(l) 10 According to the same manner as that of Reference Preparation Example 46-(1), 3-amino-4-bromo- 2-naphthoic acid was used in place of 2-amino-3, 5- dibromobenzoic acid to obtain 10-bromo-2-[3-bromo-1- (3-chloro-2-pyridinyl) -lH-pyrazol-5 yl] -4H-naphtho[2,3-d] [1, 3]oxazine- 4-one of the formula: Br N, 0 0 N Br 15 10-Bromo-2-[3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5 yl]-4H-naphtho[2,3-d] [1,3]oxazine-4-one H-NMR(DMSO-d,TMS)6(ppm):7.55(1H,s),7.

72

-

7

.

79

(

2 H,m), 7 .89 .631 (1H,t,J=8Hz),8.23(1H,d,J=8Hz),8.32(1H,d,J=8Hz),8.37(1H,dd, J=8Hz,1Hz),8.63(1H,dd,J=5Hz,1Hz),8.93(1H,s) Reference Preparation Example 105-(2) According to the same manner as that of Reference 5 Preparation Example 1,10-bromo-2-[3-bromo-1-(3-chloro-2 pyridinyl)-1H-pyrazol-5-yl]-4H-naphtho[2,3-d][1,3]oxazine-4 -one was used in place of 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-trifluoromethyl-lH pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazine-4-one to obtain 10 3-bromo-N-[1-bromo-3-(hydrazinocarbonyl)-2-naphthyl]-1-(3 chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide of the formula: Br OBr N/ N N H ci 0 NNH 3-Bromo-N- [1-bromo-3- (hydrazinocarbonyl) -2-naphthyl] -l 15 (3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide 1 H-NMR(DMSO-d,TMS)5(ppm):4.37(2H,brs),7.52(1H,s), 7 .5 9 (lH, dd,J=8Hz,4Hz),7.69(1H,t,J=8Hz),7.77(1H,t,J=8Hz),8.04-8.0 9 (2H,m),8.15(lH, d,J=8Hz),8.21(1H,d, J=8Hz),8.50 (1H,d,J=4Hz), 9.63(1H,brs),10.65(1H,brs) 20 Reference Preparation Example 106-(1) According to the same manner as that of Reference ,632 Preparation Example 71-(5), 3-amino-4-bromo-2-naphthoic acid was used in place of 2-amino-5-chloro-3-methylbenzoic acid to obtain 10-bromo-2-[4-bromo-1-(3-chloro-2-pyrid.nyl)-1H pyrrol-2-yl)-4H-naphtho[2,3-d) [1, 3]oxazine-4-one of the 5 formula: Br 0 0 N IN I Br 10-Brpmo-2- [4-bromo-1- (3-chloro-2-pyridinyl) -lH-pyrrol-2-yl )-4H-naphtho[2,3-d][1,3]oxazine-4-one 'H-NMR (DMSO-d 6 , TMS) 5 (ppm) :7. 33 (1H, d, J=2Hz) , 7. 65-7. 75 (3H, m) , 10 7.84(lH,t,J=8Hz),8.17(lH,d,J=8Hz),8.28(2H,d,J=8Hz), 8.57-8.61(1H,m),8.87(lH,s) Reference Preparation Example 106-(2) According to the same manner as that of Reference Preparation Example 71-(6), 10-bromo-2-[4-bromo-l-(3-chloro 15 2-pyridinyl)-1H-pyrrol-2-yl]-4H-naphtho[ 2 ,3-d) [1,3]oxazine 4-one was used in place of 2-[4-bromo-1-(3-chloro-2 pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one to obtain 4-bromo-N-[1-bromo-3 (hydrazinocarbonyl) -2-naphthyl] -1- (3-chloro-2-pyridinyl) -1H 20 -pyrrole-2-carboxamide of the formula: 633 Br, 0 Br N N H 0 N N H 4-Bromo-N- [1-bromo-3- (hydrazinocarbonyl) -2-naphthyl] -1- (3 chloro-2-pyridinyl)-lH-pyrrole-2-carboxamide H-NMR(DMSO-d 6 ,TMS)6(ppm)):4.37(2H,brs),7.40(lH,), 7

.

43

-

7

.

52 5 (2H,m),7.66(1H,t,J=7Hz),7.75(lH,t,J=7Hz),8.01-8.08(3H,m), 8.20(lH,d,J=8Hz),8.43(1H,d,J=5Hz), 9.55(lH,brs),10.12(lH, brs) , Reference Preparation Example 107 According to the same manner as that of Reference 10 Preparation Example 71-(6), 2-[4-bromo-1-(3-chloro-2 pyridinyl) -1H-pyrrol-2-yl] -6-cyano-8-methyl-4H- 3 , 1 benzoxazine-4-one was used in place of 2- [4-bromo-1- (3-chloro 2-pyridinyl) -1H-pyrrol-2-yll -6-chloro-8-methyl-4H-3, 1 benzoxazine-4-one to obtain 4-bromo-1-(3-chloro-2 15 pyridinyl)-N-[4-cyano-2-(hydrazinocarbonyl)-6-methylphenyl] -1H- pyrrole-2-carboxamide of the formula:

H

3 C CN Br\, O / N N H NH 2 CI O N N

H

634 4-Bromo-l-(3-chloro-2-pyridinyl)-N-[4-cyano-2 (hydrazinocarbonyl)-6-methylphenyl]-1H-pyrrole-2 carboxamide 1 H-NMR(DMSO-d 6 ,TMS)6(ppm):2.18 (3H,s),4.4 2

(

2 H,brs), 7

.

2 8 ' 5 (1H,s),7.45-7.55(2H,m),7.71(1H,s),7.84(1H,s) ,8.07(1H,d, J=8Hz),8.44(1H,d,J=4Hz),9.68(H,brs),10.16(1H,brs) Reference Preparation Example 108 According to the same manner as that of Reference Preparation Example 88, 2-[4-bromo-l-(3-chloro-2 10 pyridinyl)-lH-pyrrol-2-yl]-6-cyano-8-methyl- 4 H-3,1 benzoxazine-4-one was used in place of 2-[3-bromo-1-(3-chloro 2-pyridinyl)-1H-pyrazol-5-yl)-6-chloro-8-methyl-4H- 3 ,1 benzoxazine-4-one to obtain 3-bromo-1-(3-chloro-2 pyridinyl)-N-[4-cyano-2-(N,N'-dimethylhydrazinocarbonyl)-6 15 methylphenyl]-1H-pyrazole-5-carboxamide of the formula: Br

H

3 C CN B0 N,N N CH 3 N H NH Cl O N

H

3 C 3-Bromo-l-(3-chloro-2-pyridinyl)-N-[4-cyano-2-(N,N' dimethylhydrazinocarbonyl)-6-methylphenyl]-lH-pyrazole-5 carboxamide 20 H-NMR(DMSO-d,TMS)(ppm):2.14-2.33(6H,m),2.70-3.09( 3 H,m), 4.55-6.05(lH,m),7.37(lH,s),7.58-7.66(2H,m),7.71-7.90(lH,m), 8.15-8.21(lH,m),8.48-8.52(lH,m),10.25-10.62(lH,m) -635 Reference Preparation Example 109 To a mixture of 0.29 g of N,N'-dimethylhydrazine dihydrochloride, 1 ml of water, 0.31 g of potassium carbonate and 10 ml of N,N-dimethylformamide was added 1.0 g of 5 2-[4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrol- 2 -yl]-6 chloro-8-methyl-4H-3,1-benzoxazine-4-one. The resulting mixture was stirred at room temperature for 6 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were 10 combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 0.26 g of 4-bromo-N-[4-chloro-2-(N,N'-dimethylhydrazinocarbonyl)-6 methylphenyl] -1- (3-chloro-2-pyridinyl) -1H-pyrrole-2 15 carboxamide of the formula: Br

H

3 C C1 N CH 3 N H CIU C1 0 N N I

H

3 C 4-Bromo-N-[4-chloro-2-(N,N'-dimethylhydrazinocarbonyl)-6 methylphenyl)-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2 carboxamide 20 1 H-NMR(CDCl 3 ,TMS)8(ppm):2.16(3H,s),2.43(1H,d,J=6Hz), 2

.

6 1( 2 H, d,J=6Hz),2.95(2H,s),3.19(lH,s),3.54(0.3H,d,J=6Hz),5.62(0.7H, d,J=6Hz),7.01-7.07(3H,m),7.14-7.18(lH,m),7.30(lH,dd,J=8Hz, .636 5Hz),7.79(1H,d,J=8Hz),8.40(1H,d,J=5Hz),8.56(1H,brs) Reference Preparation Example 110-(1) According to the same manner as that of Reference Preparation Example 71-(5), 4,5-dichloro-1-(3-chloro-2 5 pyridinyl)-1H-pyrrole-2-carboxylic acid and 2-amino-3,5 dibromobenzoic acid were used in place of 4-bromo-1- (3-chloro 2-pyridinyl)-1H-pyrrole-2-carboxylic acid and 2-amino-5 chloro-3-methylbenzoic acid respectively to obtain 6,8-dibromo-2-[4,5-dichloro-1-(3-chloro-2-pyridinyl)-1H 10 pyrrol-2-yl)-4H-3,1-benzoxazine-4-one of the formula: C1 CI N ci N Br -Br 6,8-Dibromo-2-(4,5-dichloro-1-(3-chloro-2-pyridinyl)-1H pyrrol-2-yl]-4H-3,1-benzoxazine-4-one 'H-NMR(CDCl 3 ,TMS)6(ppm):7.36(lH,s),7.47(1H,dd,J=8Hz,5Hz), 15 7.95(1H,d,J=2Hz),7.99(1H,dd,J=8Hz,2Hz),8.19(lH,d,J=2Hz), 8.57(l1,dd,J=5Hz,2Hz) Reference Preparation Example 110-(2) According to the same manner as that of Reference Preparation Example 71-(6), 6,8-dibromo-2-[4,5-dichloro-l 20 (3-chloro-2-pyridinyl)-H-pyrrol-2-yl)-4H-3,1-benzoxazine-4 -one was used in place of 2- [4-bromo-1- (3-chloro-2-pyridinyl) 1H-pyrrol-2-yl]-6-chloro-8-methyl- 4H-3,1-benzoxazine-4-one ,637 to obtain N- [4, 6-dibromo-2- (hydrazinocarbonyl) phenyl) - 4 , 5 dichloro-1- (3-chloro-2- pyridinyl) -1H-pyrrole-2-carboxamide of the formula: Br Br C1 0 / B C1N N H -"NH2 CI N N N H 5 N-[4,6-dibromo-2-(hydrazinocarbonyl)phenyl]-4,5-dichloro-1 - (3-chloro-2-pyridinyl) -1H-pyrrole-2-carboxamide 1H-NMR(DMSO-d,TMS)(ppm):4.40(2H,brs), 6

.

47 (lH,s), 7

.

65 (1H,s,),7.75-7.76(1H,m),7.89(1H,s),8.05-8.06(1H,m),

B.

27 -8.

2 8 (1H,rm) ,9.64 (1H,brs) ,10.20 (1H,.brs) 10 Reference Preparation Example 111 According to the same manner as that of Reference Preparation Example 46- (1), 3-amino-4-chloro-2-naphthoic acid was used in place of 2-amino-3, 5-dibromobenzoic acid to obtain 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl)-10 15 chloro-4H-naphtho[2,3-d] [1,3]oxazine-4-one of the formula: Br Cl0 0 N cic C~t N C1 2-[3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-10 chloro-4H-naphtho[2,3-d][1,3]oxazine-4-one ,638 'H-NMR(DMSO-d 6 ,TMS)5(ppm):7.56(1H,s),7.73-7.81(2Hm), 7

.

8 9 (1H,t,J=8Hz),8.23(1H,d,J=8Hz),8.34(1H,d,J=8Hz),8.37(1H,dd, J=8Hz,1Hz),8.64(1H,dd,J=5Hz,1Hz),8.8 9 (l,s) Reference Preparation Example 112 5 According to the same manner as that of Reference Preparation Example 71- (5) , 3-amino-4-chloro-2-naphthoic acid was used in place of 2-amino-5-chloro-3-methylbenzoic acid to obtain 2- [4-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrrol-2 yl)-10-chloro-4H-naphtho[2,3-d][1,3]oxazine-4-one of the 10 formula: Br 0 0 N N C1 2- [4-Bromo-1- (3-chloro-2-pyridinyl) -1H-pyrrol-2-yl] -10 chloro-4H-naphtho[ 2 ,3-d][1,3)oxazine-4-one H-NMR (DMSO-d, TMS) 5 (ppm) :7.33 (1H, d, J=2Hz) ,7. 67 -7.

7 3 ( 2 H,m) , 15 7 .7 4 (1H,d,J=2Hz),7.82-7.87(1H,m),8.17(1H,d,J=Hz),8.26-8.31 (2H,m),8.59(lH,dd,J=5Hz,1Hz) ,8.84 (1H,s) Reference Preparation Example 113-(1) According to the same manner as that of Reference Preparation Example 71-(4), 4-chloro-1-(3-chloro-2 20 pyridinyl)-1H-pyrrole-2-carboxamide was used in place of 4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carbaldehyde .639 to obtain 4-chloro-1-(3-chloro-2-pyridinyl)-lH-pyrrole- 2 carboxylic acid of the formula: C1 N CO 2 H CI 4-Chloro-l-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxylic 5 acid H-NMR(DMSO-d 6 ,TMS)6(ppm):6.97(lH,d,J=2Hz), 7

.

4 8(lH,d,J= 2 Hz), 7.59(lH,dd,J=8Hz,5Hz),8.16(lH,dd,J=8Hz,2Hz),8.50(lH,dd, J=5Hz,2Hz) Reference Preparation Example 113-(2) 10 According to the same manner as that of Reference Preparation Example 71-(5), 4-chloro-l-(3-chloro-2 pyridinyl)-lH-pyrrole-2-cabroxylic acid was used in place of 4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxylic acid to obtain 2-[4-chloro-1-(3-chloro-2-pyridinyl)-lH 15 pyrrol-2-yl)-6-chloro-8-methyl-4H-3,1-benzoxazine-4-one of the formula: CI 0 0 N C1 N N C1

H

3 C 2-[4-Chloro-1-(3-chloro-2-pyridinyl)-lH-pyrrol-2-yl)-6- .640 chloro-8-methyl-4H-3,1-benzoxazine-4-one H-NMR(CDCl 3 ,TMS)(ppm):1.73(3H,s),7.03(H,d,J=2Hz), 7

.

2 6 (lH, d,J=2Hz),7.41(lH,d,J=2Hz),7.43(lH,dd,J=8Hz,5Hz),7.91(lH,dd, J=8Hz,2Hz),7.94(1H,d,J=2Hz),8.51(lH,dd,J=5Hz,2Hz) 5 Reference Preparation Example 113-(3) According to the same manner as that of Reference Preparation Example 71-(6), 2-(4-chloro-l-(3-chloro-2 pyridinyl)-1H-pyrrol-2-yll-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 2-[4-bromo-l-(3-chloro 10 2-pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one to obtain 4-chloro-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyridinyl )-1H-pyrrole-2-carboxamide of the formula:

H

3 C C1 N N H

-NH

2 C 0 N N H 15 4-Chloro-N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl] 1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxamide IH-NMR(CDCl 3 ,TMS)5(ppm):2.19(3H,s),6.97(1H,d,J= 2 Hz), 7 .00 (lH,d,J=2Hz),7.26(lH,s),7.30(lH,dd,J=8Hz,5Hz), 7

.

48 (lH,5), 7 .79(lH,dd,J=8Hz,2Hz),8.40(lH,dd,J=5Hz,2Hz),9.

29 (lH,brs) 20 Reference Preparation Example 114 According to the same manner as that of Reference Preparation Example 84, 2-[3-bromo-1-(3-chloro-2-pyridinyl)- .641 1H-pyrazol-5-yl]-6,8- dichloro-4H-3,1-benzoxazine-4-one was used in place of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-lH pyrazol-5-yl]-6-chloro-8-methyl-4H-3,1-benzoxazine-4-one to obtain 3-bromo-N-[4,6-dichloro-2-(N 5 methylhydrazinocarbonyl)phenyl]-1-(3-chloro-2-pyridinyl)-1H -pyrazole-5-carboxamide of the formula: CI Cl Br O N , N H - .,NH2 Cl O N N H3C 3-Bromo-N-[4,6-dichloro-2-(N-methylhydrazinocarbonyl) phenyl]-1-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxamide 10 IH-NMR(DMSO-d 6 ,TMS)5(ppm):2.76(0.6H,s),3.06(2.4H,s),4.55 (1.6H,s),5.02(0.4H,s),7.38-7.46(2.OH,m),7.60-7.64(1.OH,m), 7.71(0.8H,d,J=2Hz),7.83(0.2H,d,J=2Hz),8.17-8.20(1.OH,m), 8.51(1.OH,dd,J=5Hz,2Hz),10.38(0.8H,s),10.64(0.2H,s). Reference Preparation Example 115-(1) 15 To a solution of 3.0 g of 3-chloro-2-(lH-pyrrol-l yl)pyridine in 30 ml of N,N-dimethylformamide was added 3.1 g of N-bromosucciniimde. The resulting mixture was stirred at room temperature for 6 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl 20 acetate two times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced .642 pressure. The residue was subjected to silica gel column chromatography to obtain 1.1 g of 2-(2-bromo-lH-pyrrol-1-yl) 3-chloropyridine of the formula: BQ CI N 5 2-(2-Bromo-lH-pyrrol-1-yl)-3-chloropyridine 1H-NMR(CDCl,TMS)5(ppm):6.37-6.41(2H,m),6.

93 (lH,dd,J= 3 Hz, 2Hz) ,7. 38 (lH,dd,J=8Hz, 5Hz), 7. 91(lH,dd,J=8Hz, 2Hz) ,8. 52 (lH,dd, J=5Hz,2Hz) Reference Preparation Example 115-(2) 10 According to the same manner as that of Reference Preparation Example 71-(2), 2-(2-bromo-lH-pyrrol-1-yl) -3 chloropyridine was used in place of 3-chloro-2- (lH-pyrrol-1 yl) pyridine to obtain 5-bromo-l- (3-chloro-2-pyridinyl) -lH pyrrole-2-carbaldehyde of the formula: Br N>CHO CIN 15 5-Bromo-l-(3-chloro-2-pyridinyl)-lH-pyrrole-2-carbaldehyde 1H-NMR(CDCl 3 ,TMS)6(ppm):6.53(lH,d,J=4Hz),7.07(lH,d,J= 4 Hz), 7.45(1H,dd,J=8Hz,5Hz),7.92(lH,dd,J=8Hz,2Hz),8.54(lH,dd, J=5Hz,2Hz) ,9.36(lH,s) .643 Reference Preparation Example 115-(3) According to the same manner as that of Reference Preparation Example 71-(4), 5-bromo-1-(3-chloro-2 pyridinyl)-1H-pyrrole-2-carbaldehyde was used in place of 5 4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carbaldehyde to obtain 5-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2 carboxylic acid of the formula: .BrN

CO

2 H CIN 5-Bromo-1- (3-chloro-2-pyridinyl) -1H-pyrrole-2-carboxylic 10 acid 1H-NMR(DMSO-d6,TMS)5(ppm):6.54(H,d,J=4Hz),7.0 2 (lH,d,J= 4 Hz), 7 .63(lH,dd,J=8Hz,5Hz),8.21(lH,d,J=8Hz),8.56(1H,d,J=5Hz), 12. 54 (1H, brs) Reference Preparation Example 115-(4) 15 According to the same manner as that of Reference Preparation Example 71- (5) , 5-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrrole-2-carboxylic acid was used in place of 4-bromo-l (3-chloro-2-pyridinyl) -1H- pyrrole-2-carboxylic acid to obtain 2-[5-bromo-1- (3-chloro-2-pyridinyl)-1H-pyrrol-2 20 yl)-6-chloro-8-methyl-4H- 3 ,1-benzoxazine-4-one of the formula: 644 0 0 BrO N C1 N N H 3 C C 2-(5-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrol-2-yl]-6 chloro-8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR(CDC1 3 ,TMS)5(ppm):1.57(3H,s),6.55(1H,d,J= 4 Hz), 7

.

33 5 (1H,d,J=4Hz),7.38(H,d,J=2Hz),7.47(1H,dd,J=BHz,5Hz), 7

.

92 (1H,d,J=2Hz),7.97(1H,dd,J=8Hz,2Hz),8.59(1H,dd,J=5Hz, 2 Hz) Reference Preparation Example 115-(5) According to the same manner as that of Reference Preparation Example 71-(6), 2,-[5-bromo-1-(3-chloro-2 10 pyridinyl)-H-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1-benzoxa zine-4-one was used in place of 2-[4-bromo-1-(3-chloro-2 pyridinyl)-lH-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one to obtain 5-bromo-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(3-chloro-2-pyridinyl 15 )-1H-pyrrole-2-carboxamide of the formula:

H

3 C Cl 0 Br0 N N H 5-Bromo-N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl] 1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxamide ,645 1 H-NMR(CDCl 3 ,TMS)6(ppm):2.17(3H,s),4.02(2H,brs), 6

.

4 7 (lH,d, J=4Hz),7.03(1H,d,J=4Hz),7.20(1H,s),7.27(1H,S),7.36(1H,dd, J=8Hz, 5Hz) 7.86(1H,dd, J=8Hz, 2Hz) ,8. 40 (1H,dd, J=5Hz,2Hz), 9. 22 (1H, brs) 5 Reference Preparation Example 116-(l) A mixture of 1.9 g of 2-pyrrolecarbaldehyde, 2.3 g of 2-chloropyrimidine, 7.8 g of cesium carbonate and 20 ml of N-methylpyrrolidone was stirred at 130 0 C for 13 hours, and then allowed to cool to room temperature. Water was poured into the 10 reaction mixture, and the mixture was extracted with ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was 15 subjected to silica gel chromatography to obtain 0.94 g of 1-(2-pyrimidinyl)-1H-pyrrole-2-carbaldehyde of the formula: H N N N 1-(2-Pyrimidinyl)-lH-pyrrole-2-carbaldehyde 'H-NMR (CDCl3, TMS) 6(ppm) :6.40-6.41 (1H,m),7.22 (1H, t, J=5Hz) , 20 7.29(lH,dd,J=4Hz,2Hz),7.96(lH,dd,J=3Hz,2Hz),8.73(2H,d, J=5Hz),10.61(1H,s) Reference Preparation Example 116-(2) To a solution of 0.5 g of 1-(2-pyrimidinyl)-1H-pyrrole-2- 646 carbaldehyde in 10 ml of N,N-dimethylformamide was added 0.6 g of N-bromosuccinimide. The resulting mixture was stirred at room temperature for 1 hour. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate two' 5 times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 0.43 g of 5-bromo-1-(2 10 pyrimidinyl)-lH-pyrrole-2-carbaldehyde of the formula: Br H N N 5-Bromo-l-(2-pyrimidinyl)-1H-pyrrole-2-carbaldehyde lH-NMR(DMSO-d 6 ,TMS)6 (ppm) :6. 67 (1H, d, J=4Hz) ,7. 28 (lH,d, J=4Hz), 7.75(lH,t,J=5Hz),9.02(2H,d,J=5Hz),9.39(1H,s) 15 Reference Preparation Example 116-(3) A solution of 2.0 g of potassium permanganate in 10 ml of water was added dropwise to a mixture of 0.76 g of 5-bromo-l-(2-pyrimidinyl)-lH- pyrrole-2-carbaldehyde and 18 ml of acetone while the mixture was maintained at 40*C. The 20 resulting mixture was stirred at 40*C for 4 hours. A precipitate was filtered off to obtain a filtrate. The filtrate was adjusted to pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution, and then washed with chloroform two times.

,647 The aqueous layer was adjusted to around pH 3 by an addition of 2N hydrochloric acid, and then extracted with ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium 5 chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 0.28 g of 5-bromo-l-(2-pyrimidinyl)-lH- pyrrole-2-carboxylic acid of the formula: OH Br N, O 10 5-Bromo-l-(2-pyrimidinyl)-lH-pyrrole-2-carboxylic acid H-NMR(DMSO-d,TMS)6(ppm):6.40-6.51(lH,m), 6 .89- 7 .1 6 (lH,m), 7.66-7.75(lH,m),8.99(2H,d,J=5Hz) Reference Preparation Example 116-(4) According to the same manner as that of Reference 15 Preparation Example 71-(5), 5-bromo-l-(2-pyrimidinyl)-lH pyrrole-2-carboxylic acid was used in place of 4-bromo-1-(3 chloro-2-pyridinyl)-lH-pyrrole-2-carboxylic acid to obtain 2-[5-bromo-1-(2-pyrimidinyl)-1H-pyrrol-2-yl)-6-chloro-8 methyl-4H-3,1-benzoxazine-4-one of the formula: 0 0 Br N N N N 20

H

3 C C .

.648 2-(5-Bromo-1-(2-pyrimidinyl)-1H-pyrrol- 2 -yl)-6-chloro-8 methyl-4H-3,1-benzoxazine-4-one 'H-NMR(DMSO-d,TMS)(ppm):1.67(3H,s),6.62(1H,d,J=4Hz), 7

.

2 0 7.30(1H,m),7.67-7.72(1H,m),7.77-7.88(2H,m),9.06-9.12(2H,m) 5 Reference Preparation Example 116-(5) According to the same manner as that of Reference Preparation Example 71-(6), 2-[5-bromo-l-(2 pyrimidinyl)-1H-pyrrol-2-yl)-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 2- [4-bromo-1- (3-chloro 10 2-pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8-methyl- 4 H-3,1 benzoxazine-4-one to obtain 5-bromo-N-(4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(2-pyrimidinyl)-1H pyrrole-2-carboxamide of the formula:

H

3 C C1 0 Br N H -NH2 O N N N H 15 5-Bromo-N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl] 1-(2-pyrimidinyl)-lH-pyrrole-2-carboxamide H-NMR(DMSO-d 6 ,TMS)5(ppm):2.13(3H,s),6.45(1H,d,J= 4 Hz), 7 .12 (lH,brs),7.30(1H,brs),7.44(1H,brs),7.59-7.6 6 (lH,m), 8

.

90 8.95(2H,m),9.51(1H,brs),9.92(1H,brs) 20 Reference Preparation Example 117-(l) A mixture of 5 g of 2,6-dichloroaniline, 4.5 g of 649 2,5-dimethoxytetrahydrofuran and 30 ml of acetic acid was heated to reflux for 10 hours. The reaction mixture was allowed to cool, poured into water, and extracted with ethyl acetate two times. The organic layers were combined, washed 5 successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 5.45 g of .-(2,6-dichlorophenyl)-1H-pyrrole of the formula: N 10 Cl CI 1-(2,6-Dichlorophenyl)-1H-pyrrole 'H-NMR (DMSO-d 6 , TMS) 6 (ppm) :6.26 (2H, t, J=2Hz) ,6.82 (2H, t, J=2Hz) ,7.50(lH,t,J=8Hz),7.66(2H,d,J=8Hz) Reference Preparation Example 117-(2) 15 Under ice-cooling, 7.67 g of phosphorus oxychloride was added dropwise to 4 g of N,N-dimethylformamide. The mixture was stirred at room temperature for 30 minutes, and 2.1 g of 1-(2,6-dichlorophenyl)-lH-pyrrole was added thereto. The resulting mixture was stirred at 60 0 C for 2 hours, allowed to 20 cool to room temperature, and then poured into ice water. The mixture was adjusted to pH 4 by an addition of a 2N aqueous sodium hydroxide solution, and then extracted with ethyl acetate two times. The organic layers were combined, washed 650 successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 0.80 g'of 5 1-(2,6-dichlorophenyl)-1H-pyrrole-2-carbaldehyde of the formula: H N 7Y and 1.00 g of l-(2,6-dichlorophenyl)-lH-pyrrole-3 carbaldehyde of the formula: H N 10 C I C1 1-(2,6-Dichlorophenyl)-1H-pyrrole-2-carbaldehyde H-NMR (DMSO-d6, TMS) 6 (ppm) : 6. 54 (lH, dd, J=4 Hz, 3Hz) , 7. 2 9 (lH, dd, J=4Hz,2Hz),7.35(lH,ddd,J=3Hz,2Hz,1Hz),7.53(lH,dd,J=9Hz,7Hz), 15 7.63-7.67 (2H,rm) ,9.50(lH,d,J=lHz) 1-(2,6-Dichlorophenyl)-lH-pyrrole-3-carbaldehyde 1 H-NMR (DMSO-d, TMS) 6 (ppm) : 6. 69 (1H, dd, J=3, 2 Hz) , 7. 07 (1H, ddd, J=3Hz,2Hz,1Hz),7.58(lH,dd,J=9Hz,8Hz),7.71- 7

.

7 5(2H,m), 20 7.85(1H,brs),9.78(1H,d,J=lHz) ,651 Reference Preparation Example 117-(3) In 10 ml of N,N-dimethylformamide was dissolved 0.65 g of 1- (2, 6-dichlorophenyl) -1H-pyrrole-2-carbaldehyde, and then 0.53 g of N-bromosuccinimide was added thereto. The mixture' 5 was stirred at room temperature for 1 hour. Water was poured into the reaction mixture, a deposited precipitate was collected by filtration to obtain 0.85 g of 4-bromo-1-(2,6 dichlorophenyl)-lH-pyrrole-2-carbaldehyde of the formula: Br H N CIO 10 4-Bromo-1- (2, 6-dichlorophenyl) -lH-pyrrole-2-carbaldehyde 'H-NMR (DMSO-d 6 , TMS) 5 (ppm) :7. 4 3 (lH, d, J=2Hz) , 7. 56 (1H, dd, J=9Hz ,7Hz),7.65-7.69(3H,m),9.46(lH,s) Reference Preparation Example 117-(4) A solution of 2.0 g of potassium permanganate in 10 ml of 15 water was added dropwise to a mixture of 0.85 g of 4-bromo-1- (2, 6-dichlorophenyl) --1H-pyrrole-2-carbaldehyde and 18 ml of acetone while the mixture was maintained at 40 0 C. The resulting mixture was stirred at 40 0 C for 2 hours. A precipitate was filtered off to obtain a filtrate. The filtrate 20 was adjusted to pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution, and then extracted with chloroform two times. The aqueous layer was adjusted to around pH 3 by an 652 addition of 2N hydrochloric acid, and then extracted with ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and 5 concentrated under reduced pressure to obtain 0.66 g of 4-bromo-l- (2, 6-dichlorophenyl) -1H-pyrrole-2-carboxylic acid of the formula: Br OH N ClO 4-Bromo-l- (2, 6-dichlorophenyl) -1H-pyrrole-2-carboxylic acid 10 1H-NMR (DMSO-d, TMS)6(ppm) :7.05 (1H, brs),7.40 (lH, brs), 7 .51(lH ,t,J=8Hz),7.60-7.67(2H,m),12.65(lH,s) Reference Preparation Example 117-(5) According to the same manner as that of Reference Preparation Example 71-(5), 4-bromo-1-(2, 6-dichlorophenyl) 15 1H-pyrrole-2-carboxylic acid was used in place of 4-bromo-1 (3-chloro-2-pyridinyl)-1H- pyrrole-2-carboxylic acid to obtain 2-[4-bromo-1-(2, 6-dichlorophenyl)-1H-pyrrol-2-yl)-6 chloro-8-methyl-4H-3,1-benzoxazine-4-one of the formula: Br 0 0 N I C'

H

3 C C ,653 2-[4-Bromo-1-(2,6-dichlorophenyl)-1H-pyrrol-2-yl]-6-chloro -8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR(DMSO-cd6 ,TMS)(ppm):1.68(3H,s),7.32(lH,d,J=lHz), 7.54-7.64(2H,m),7.67-7.77(3H,m),7.83(1H,d,J=2Hz) 5 Reference Preparation Example 117-(6) According to the same manner as that of Reference Preparation Example 71-(6), 2-[4-bromo-l-(2,6 dichlorophenyl)-1H-pyrrol-2-yl)-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 2-[4-bromo-1-(3 10 chloro-2-pyridinyl)-lH-pyrrol-2-yl]-6-chloro-8-methyl-4H- 3 , 1-benzoxazine-4-one to obtain 4-bromo-N-[4-chloro-2 (hydrazinocarbonyl)-6-methylphenyl]-1-(2,6-dichlorophenyl) 1H-pyrrole-2-carboxamide of the formula: Br 0H 3 C Ci N N H -NH2 C1 C1 O N H 15 4-Bromo-N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl] 1-(2,6-dichlorophenyl)-lH-pyrrole-2-carboxamide H-NMR(DMSO-d 6 ,TMS)5(ppm):2.11(3H,s),4.38(2H,brs), 7

.

2 7

-

7 .30

(

2 H,m),7.34(1H,d,J=2Hz),7.40-7.46(2H,m),7.56( 2 H,d,J=BHz), 9.51(1H,brs),9.81(1H,brs) 20 Reference Preparation Example 118-(1) A mixture of 2.6 g of 2-pyrrolecabaldehyde, 5.0 g of 654 3, 4,5-trichloropyridine, 10.7 g of cesium carbonate and 30 ml of N-methylpyrrolidone was stirred at 100*C for 2 hours, and then allowed to cool to room temperature. Water was poured into the reaction mixture, and the mixture was extracted with ethyl' 5 acetate two times. The organic layers were combined, washed successively water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 2.14 g of 10 1- (3, 5-dichloro-4-pyridinyl) -1H-pyrrole-2-carbaldehyde of the formula: SH N, ClCO N 1-(3,5-Dichloro-4-pyridinyl)-1H-pyrrole-2-carbaldehyde 'H-NMR(DMSO-d 6 ,TMS)6(ppm) :6.61(lH,dd,J=4Hz,3Hz),7.37(1H,dd, 15 J=4Hz,2Hz),7.46(lH,ddd,J=3Hz,2Hz,1Hz),8.85(2H,s), 9 .5 4 (lH,d, J=lHz) Reference Preparation Example 118-(2) To a solution of 2.14 g of 1-(3,5-dichloro-4-pyridinyl) 1H-pyrrole-2-carbaldehyde in 10 ml of N,N-dimethylformamide 20 was added 1.7 g of N-bromosuccinimide. The mixture was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by 655 filtration to obtain 2.9 g of 4-bromo-1-(3,5-dichloro-4 pyridinyl)-lH-pyrrole-2-carbaldehyde of the formula: Br H N CIN Cl1 N 4-Bromo-1- (3, 5-dichloro-4-pyridinyl) -1H-pyrrole-2 5 carbaldehyde 'H-NMR(DMSO-d 6 ,TMS) 6 (ppm) :7. 52 (lH,d, J=2Hz) ,7.74 (1H,dd, J=2Hz, 1Hz),8.88(2H,s),9.51(lH,d,J=lHz) Reference Preparation Example 118-(3) A solution of 2.9 g of potassium permanganate in 15 ml of 10 water was added dropwise to a mixture of 2.86 g of 4-bromo-l-(3,5-dichloro-4-pyridinyl)-lH-pyrrole-2 carbaldehyde and 30 ml of acetone while the mixture was maintained at 40"C. The mixture was stirred at 40 0 C for 2 hours. A precipitate was filtered off to obtain a filtrate. The 15 filtrate was adjusted to pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution, and then washed with chloroform two times. The aqueous layer was adjusted to around pH 3 by an addition of 2N hydrochloric acid. A deposited precipitate was collected by filtration to obtain 2.08 g of 4-bromo-l-(3,5 20 dichloro-4-pyridinyl)-H-pyrrole-2-carboxylic acid of the formula: 656 Br OH N CIN Cl~C N 4-Bromo-1- (3, 5-dichloro-4-pyridinyl) -lH-pyrrole-2 carboxylic acid 1H-NMR (DMSO-d,, TMS) 6 (ppm) :7. 12 (1H, d, J=2Hz) ,7. 51 (lH, d, J= 2 Hz) , 5 8.85(2H,s) Reference Preparation Example 118-(4) According to the same manner as that of Reference Preparation Example 71-(5), 4-bromo-1-(3,5-dichloro-4 pyridinyl)-lH-pyrrole-2-carboxylic acid was used in place of 10 4-bromo-l- (3-chloro-2-pyridinyl) -1H- pyrrole-2-carboxylic acid to obtain 2-[4-bromo-1-(3,5-dichloro-4 pyridinyl) -1H-pyrrol-2-yl) -6-chloro-8-methyl-4H-3, 1 benzoxazine-4-one of the formula: Br 0 O N CI N N H 3 C CI 15 2-[4-Bromo-1- (3, 5-dichloro-4-pyridinyl) -1H-pyrrol-2-yl]-6 chloro-8-methyl-4H-3, 1-benzoxazine-4-one 1H-NMR(DMSO-d 6 ,TMS)5(ppm) :1.64 (3H,s) , 7

.

39 (lH,brs) , 7.72(2H,s),7.85(lH,brs),8.95(2H,s) Reference Preparation Example 118-(5) 657 According to the same manner as that of Reference Preparation Example 71-(6), 2-[4-bromo-1-(3,5-dichloro-4-pyridinyl)-1H-pyrrol 2-yl)-6-chloro-8-methyl-4H-3,1-benzoxazine-4-one was used iri 5 place of 2-[4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrol-2 yl)-6-chloro-8-methyl-4H-3,1-benzoxazine-4-one to obtain 4-bromo-N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl)-1 - (3, 5- dichloro-4-pyridinyl) -1H-pyrrole-2-carboxamide of the formula:

H

3 C C1 N N H -NH2 CI C1 0 N H 10 N 4-Bromo-N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyll 1- (3, 5-dichloro-4-pyridinyl) -1H-pyrrole-2-carboxamide H-NMR(DMSO-d,, TMS) 5 (ppm) :2. 13 (3H, s), 4. 35 (2H,brs) , 7

.

28 (1H, d, J=2Hz),7.37(1H,d,J=2Hz),7.43-7.47(2H,m),8.

7 6

(

2 H,s), 15 9.52(lH,brs),9.89(1H,brs) Reference Preparation Example 119-(1) A solution of 0.9 g of potassium permanganate in 10ml of water was added dropwise to a mixture of 0.58 g of 1- (2, 6-dichlorophenyl) -1H-pyrrole-3-carbaldehyde and 20 ml of 20 acetone while the mixture was maintained at 40 0 C. The resulting mixture was stirred at 40*C for 2 hours. A deposited ,658 precipitate was filtered off to obtain a filtrate. The filtrate was adjusted to pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution, and then washed with chloroform two times. The aqueous layer was adjusted to around pH 3 by an addition' 5 of 2N hydrochloric acid, and then extracted with ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 0.34 g of 10 1-(2,6-dichlorophenyl)-1H-pyrrole-3-carboxylic acid of the formula: 0 OH N C111 C1 1- (2, 6-Dichlorophenyl) -1H-pyrrole-3-carboxylic acid H-NMR(DMSO-d 6 , TMS) 6 (ppm) :6. 60 (1H, dd, J=3Hz, 2Hz), 6. 92 (lH,dd, 15 J=3Hz,1Hz),7.48(lH,dd,J=2Hz,1Hz),7.55(lH,dd,J= 8 Hz, 7 Hz), 7.67-7.72 (2H,m) ,12.05 (1H,brs) Reference Preparation Example 119-(2) According to the same manner as that of Reference Preparation Example 71-(5), 1-(2, 6-dichlorophenyl)-lH 20 pyrrole-3-carboxylic acid was used in place of 4-bromo-1 (3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxylic acid to obtain 6-chloro-2- [1- (2, 6-dichlorophenyl) -1H-pyrrol-3- ,659 yl]-8-methyl-4H-3,1-benzoxazine- 4 -one of the formula: CI

H

3 C CI 6-Chloro-2- [1- (2, 6-dichlorophenyl) -1H-pyrrol-3-yll -8 methyl-4H-3,1-benzoxazine-4-one 5 1H-NMR(DMSO-d 6 ,TMS)5(ppm):2.53(3H,s),6.89(H,s), 7 .10(1H,s), 7.43-7.64 (2H,m),7.67-7.77 (2H,m),7.82-7.91(2H,m) Reference Preparation Example 119-(3) According to the same manner as that of Reference Preparation Example 71-(6), 6-chloro-2-[l-(2,6 10 dichlorophenyl)-1H-pyrrol-3-yl]-8-methyl-4H-3,1-benzoxazine -4-one was used in place of 2-[4-bromo-l-(3-chloro-2 pyridinyl) -1H-pyrrol-2-yl] -6-chloro-8-methyl-4H- 3 , 1 benzoxazine-4-one to obtain N-(4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -l- (2, 6-dichlorophenyl) 15 1H-pyrrole-3-carboxamide of the formula:

H

3 C Ci 0 / N C1 N' H O N'NH2 0 N~I H \CI N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl] -l (2,6-dichlorophenyl)-1H-pyrrole-3-carboxamide 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.22(3H,s),4.5 9

(

2 H,brs),6.

79 (lH, -660 brs),6.97(lH,brs),7.37(lH,brs),7.47-7.59(3H,m),7.71(2H,d, J=8Hz),9.66(1H,brs),9.70(lH,brs) Reference Preparation Example 120 To a mixture of 4.61 g of methylhydrazine, 25 ml of 5 methanol and 4.0 g of sodium hydroxide was added dropwise 10.8 g of N,N-dimethylcarbamoyl chloride under ice-cooling. The mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was distilled 10 under reduced pressure (90 to 99*C/22 mmHg) to obtain 5.70 g of 2,,4,4-trimethylsemicarbazide of the formula: CH3 H2N'N N(CH 3

)

2 0 2,4,4-Trimethylsemicarbazide 'H-NMR(CDCl 3 ,TMS)5(ppm):2.90 (6H,s),2.95(3H, s), 3

.

94

(

2 H,brs) . 15 Reference Preparation Example 121 According to the same manner as that of Reference Preparation Example 101, 2-[4,5-dichloro-1-(3-chloro-2 pyridinyl) -lH-pyrrol-2-yll-6-chloro-8-methyl-4H-3, 1 benzoxazine-4-one was used in place of 2- [4-bromo-l- (3-chloro 20 2-pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one to obtain 4,5-dichloro-N-[4-chloro-2-(N methylhydrazinocarbonyl) -6-methylphenyl] -1- (3-chloro-2 pyridinyl)-1H-pyrrole-2-carboxamide of the formula: 661

H

3 C CI N C1 N H -.. NH2 CI N H

H

3 C 4, 5-Dichloro-N- [4-chloro-2- (N-methylhydrazinocarbonyl) -6 methylphenyl] -1- (3-chloro-2-pyridinyl) -1H-pyrrole-2-carboxa mide 5 'H-NMR(CDCl 3 ,TMS)5(ppm):2.01-2.05(3H,m), 2

.

92

(

2 H,s), 3.21(lH,s),4.05(0.7H,brs),4.59(l.3H,brs),6.95-7.10( 2 H,m), 7 .19(0.6H,s),7.29(0.4H,s),7.37(1H,dd,J=8Hz,4Hz),7.86(1H,d, J=8Hz,),8.48(1H,d,J=5Hz),9.11(0.6H,brs),9.42(0.4H,brs) Reference Preparation Example 122-(1) 10 According to the same manner as that of Reference Preparation Example 13, 1-[(2-fluoro-3-pyridinyl) methyl]-3-trifluromethyl-1H-pyrazole-5-carboxylic acid was used in place of 1-(3-chloro-2-pyridinyl)-H-pyrazole-5 carboxylic acid to obtain 6-chloro-2-[l-[(2-fluoro-3 15 pyridinyl)methyl]-3-trifluoromethyl-H-pyrazol-5-yl)-8 methyl-4H-3,1- benzoxazine-4-one of the formula:

F

3 C N, 0 0 F N 1 NN NN.ICH2 ~

H

3 C .CI 6-Chloro-2-[l-[ (2-fluoro-3-pyridinyl)methyl] -3 trifluoromethyl-1H-pyrazol-5-yl) -8-methyl-4H-3, 1- .662 benzoxazine-4-one 'H-NMR(DMSO-d 6 ,TMS)(ppm):2.25(3H,s),6.1 6

(

2 H,s), 7.30-7.36(lH,m) ,7.39-7.46(1H,m) ,7.69(lH, s) ,7.90 (1H,d, J=2Hz), 7.98(1H,d,J=2Hz),8.20(1H,d,J=4Hz) 5 Reference Preparation Example 122-(2) According to the same manner as that of Reference Preparation Example 1, 6-chloro-2- [1- [ (2-fluoro-3-pyridinyl) methyl]-3-trifluoromethyl-1H-pyrazol-5-yl]-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 10 6-chloro-2-[1-(3-chloro 2-pyridinyl)-3-trifluoromethyl-H-pyrazol-5-yl]-8-methyl-4H -3,1-benzoxazine-4-one to obtain N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -1- [(2-fluoro-3 pyridinyl)methyl]-3-trifluoromethyl-lH-pyrazole-5 15 carboxamide of the formula:

F

3 C

H

3 C Cl F N H NH2

CH

2 0 N N H N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl) -1 [ (2-fluoro-3-pyridinyl)methyl] -3-trifluoromethyl-1H pyrazole-5-carboxamide 20 'H-NMR(DMSO-d 6 ,TMS)(ppm):2.13(3H,s),4.

3 7

(

2 H,brs), 5.86 (2H, s),7.32-7.3 8 (2H,m) ,7.50-7.57 (2H,m) ,7.57-7.64 (lH,m), 8.16-8.21(1H,m),9.62(lH,brs),10.28(1H,brs) 663 Reference Preparation Example 123-(l) According to the same manner as that of Reference Preparation Example 13, 1-( (3-chloro-2-pyridinyl)methyl)-5 trifluoromethyl-1H- pyrazole-3-carboxylic acid was used in 5 place of 1-(3-chloro- 2-pyridinyl)-1H-pyrazole-5-carboxylic acid to obtain 2-[1-[(3-chloro-2-pyridinyl)methyl]-5 trifluoromethyl-H-pyrazol-3-yl] -6-chloro-8-methyl-4H-3, 1 benzoxazine-4-one of the formula:

F

3 C HCN, 1 0 0

H

2 C. N N N

H

3 C CI 10 2-[l-[ (3-Chloro-2-pyridinyl)methyl]-5-trifluoromethyl-lH pyrazol-3-yl] -6-chloro-8-methyl-4H- 3 , 1-benzoxazine-4-one 1H-NMR(DMSO-d 6 ,TMS)5 (ppm) :2. 56 (3H,s) ,5. 92 (2H, s), 7. 44 (lH,dd, J=8Hz,5Hz),7.67(lH,s),7.89-7.95(2H,m),8.04(lH,d,J=8Hz), 8.42 (lH,d,J=5Hz) 15 Reference Preparation Example 123-(2) According to the same manner as that of Reference Preparation Example 1, 2-[1-[ (3-chloro-2-pyridinyl)methyl] -5-trifluoromethyl-1H-pyrazol-3-yl)-6-chloro-8-methyl-4H- 3 , 1-benzoxazine-4-one was used in place of 6-chloro-2-[l-( 3 20 chloro-2-pyridinyl) -3-trifluoromethyl-lH-pyrazol-5-yl] -8 methyl-4H-3,1-benzoxazine-4-one to obtain N-[4-chloro-2 (hydrazinocarbonyl) -6-methylphenyl] -l- [(3-chloro-2- .664 pyridinyl)methyl)-5-trifluoromethyl-1H-pyrazole- 3 carboxamide of the formula:

H

3 C C1 0 F 3 C , N N N-N H NH2 C/O N

OH

2 H Cl N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl] -- [(3 5 chloro-2-pyridinyl)methyl]-5-trifluoromethyl-1H-pyrazole- 3 carboxamide 'H-NMR (DMSO-d 6 , TMS) 5 (ppm) :2.19 (3H, s) , 4. 45 (2H, brs) , 5. 87 (2H,s),7.37(lH,brs),7.41-7.50(2H,m),7.52(1H,brs),8.0 4 (lH,d, J=8Hz),8.45(1H,d,J=4Hz),9.71(1H,brs),10.12(1H,brs) 10 Reference Preparation Example 124-(1) To a solution of 5.0 g of 3-chloro-2-(2-formyl-lH-pyrrol 1-yl)pyridine in 50 ml of N,N-dimethylformamide was added 5.4 g of N-iodosuccinimide. The resulting mixture was stirred at room temperature for 1 day. Water was poured into the reaction 15 mixture, and the mixture was extracted with ethyl acetate two times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography 20 to obtain 3. 2 g of 1- (3-chloro-2-pyridinyl) -4 -odo-1H-pyrrole -2-carbaldehyde of the formula: ,665 N CHO CI N and 0.90 g of 1-(3-chloro-2-pyridiny1)-5-iodo-1H-pyrrole 2-carbaldehyde of the formula: I N CHO ClN

I

5 1- (3-Chloro-2-pyridinyl) -4-iodo-.1H-pyrrole-2-carbaldehyde 1H-NMR(CDC 3 ,TMS)(ppm):7.19-7.20(2H,m),7.

3 8- 7

.

42 (lH,m), 7.89(1H,d,J=8Hz),8.45-8.47(1H,m),9.51(lH,s) 1- (3-Chloro-2-pyridinyl) -5-iodo-lH-pyrrole-2-carbaldehyde 10 1H-NMR(CDCl 3 ,TMS)6(ppm):6.72(lH,d,J=4Hz),7.0 4 (lH,d,J=4Hz), 7

.

47 (1H,dd,J=8Hz,5Hz),7.93(1H,dd,J=BHz,2Hz),8.

55 (lH,dd, J=5Hz,2Hz),9.26(1H, s) Reference Preparation Example 124-(2) According to the same manner as that of Reference 15 Preparation Example 71-(4), 1-(3-chloro-2-pyridinyl)-4 iodo-1H-pyrrole-2-carbaldehyde was used in place of 4-bromo-l (3-chloro-2-pyridinyl) -1H-pyrrole-2-carbaldehyde to obtain 1- (3-chloro-2-pyridinyl) -4-iodo-lH-pyrrole-2-carboxylic acid of the formula: ,666 N CO 2 H CI 1- (3-Chloro-2-pyridinyl) -4-iodo-lH-pyrrole-2-carboxylic acid 'H-NMR (DMSO-d 6 , TMS) 6 (ppm) :7. 05 (1H, d, J=2Hz) ,7.4 5 (1H, d, J=2Hz) , 5 7.57(1H,dd,J=8Hz,5Hz) ,8.15(1H,dd,J=BHz,2Hz),8.49(1H,dd, J=5Hz,2Hz) ,12.65(1H,brs) Reference Preparation Example 124-(3) According to the same manner as that of Reference Preparation Example 71-(5), 1-,(3-chloro-2-pyridinyl)-4-iodo 10 1H-pyrrole-2-carboxylic acid was used in place of 4-bromo-1 (3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxylic acid to obtain 6-chloro-2-[1-(3-chloro-2-pyridinyl) -4-odo-1H pyrrol-2-yl]-8-methyl-4H-3,1-benzoxazine-4-one of the formula: S0 0 C1 N / N CI P&C 15

H

3 C 6-Chloro-2- [1- (3-chloro-2-pyridinyl) -4-iodo-1H-pyrrol 2-yl) -8-methyl-4H-3, 1-benoxazine-4-one H-NMR(CDCl 3 ,TMS)5(ppm):1.67(3H,s),7.30(lH,d,J= 2 Hz), 6 67 7.61(lH,d,J=2Hz),7.63-7.67(2H,m),7.82(1H,d,J=3Hz), 8.22(lH,dd,J=8Hz,2Hz),8.56(1H,dd,J=5Hz,2Hz) Reference Preparation Example 124-(4) According to the same manner as that of Reference 5 Preparation Example 71- (6), 6-chloro-2-[1-(3-chloro- 2 pyridinyl)-4-iodo-1H-pyrrol-2-yl]-8-methyl-4H- 3 ,1 benzoxazine-4-one was used in place of 2- [4-bromo-1- (3-chloro 2-pyridinyl)-1H-pyrrol-2-yl)-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one to obtain N-[4-chloro-2 10 (hydrazinocarbonyl)-6-mehtylphenyl]-1-(3-chloro-2-pyridinyl )-4-iodo-lH-pyrrole-2-carboxamide of the formula:

H

3 C C1 N N H NH2 C1 0 N N H N-[4-chloro-2-(hydrazinocarbonyl)-6-mehtylphenyl]-1-(3 chloro-2-pyridinyl)-4-iodo-lH-pyrrole-2-carboxamide 15 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.13(3H,s),4.39(2H,brs), 7.26(1H,s),7.30(lH,s),7.39(1H,s),7.42(1H,s),7.49(1H,dd, J=8Hz,5Hz),8.05(1H,dd,J=8Hz,2Hz),8.43(lH,dd,J=5Hz,2Hz), 9.52(lH,brs),9.84(lH,brs) Reference Preparation Example 125 20 According to the same manner as that of Reference Preparation Example 71-(5), 4,5-dichloro-l-(3-chloro-2- .668 pyridinyl) -1H-pyrrole-2-carboxylic acid and 3-amino-7-bromo 4-chloro-2-naphthoic acid were used in place of 4-bromo-1 (3-chloro-2-pyridinyl)-lH-pyrrole- 2-carboxylic acid and 2-amino-5-chloro-3-methylbenzoic acid respectively to obtain 5 10-chloro-2-[4,5-dichloro-1-(3-chloro-2-pyridinyl)-lH pyrrol-2-yl)-4H-naphtho[2,3-d] [1,3]oxazine-4-one of the formula: CI CI N N Cit C. 10-Chloro-2- [4, 5-dichloro-1- (3-chloro-2-pyridinyl) -1H 10 pyrrol-2-yl]-4H-naphtho[2,3-d) [1,3)oxazine-4-one 1H-NMR(DMSO-d 6 , TMS)6(ppm):7.51(1H, s),7.70 (1H,t, J=8Hz), 7

.

78 (1H,dd,J=8Hz,5Hz),7.84(1H,t,J=8Hz),8.16(1H,d,J=8Hz),8.

28 (lH, d,J=8Hz),8.40(1H,dd,J=8Hz,2Hz),8.68(1H,dd,J=5Hz, 2 Hz),8.

82 (1H,s) 15 Reference Preparation Example 126-(1) To 30 ml of acetic acid were added 5.0 g of 2-chloro-3 pyridinylamine and 5.6 g of 2, 5-dimethoxytetrahydrofuran, and the mixture was heated to reflux for 2 hours. The reaction mixture was allowed to cool to room temperature, poured into 20 water, and then extracted with ethyl acetate two times. The organic layers were combined, washed successively with water ,669 and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 6.5 g of 1- (2-chloro-3-pyridinyl) -lH-' 5 pyrrole of the formula: N C1 1-(2-Chloro-3-pyridinyl)-1H-pyrrole 'H-NMR(DMSO-d 6 ,TMS) 6 (ppm) :6.29 (2H,t, J=2Hz) ,7.09 (2H,t, J=2Hz), 7.58(1H,dd,J=8H,5Hz),7.95(lH,dd,J=8H,2Hz),8.45(lH,dd,J=5H, 10 2Hz) Reference Preparation Example 126-(2) To 14.6 g of N,N-dimethylformamide was added dropwise 8.3 g of phosphorus oxychloride under ice-cooling. The mixture was stirred at room temperature for 30 minutes. Thereto 6.5 g of 15 1-(2-chloro-3-pyridinyl)-1H-pyrrole was added, and the resulting mixture was stirred at 60*C for 2 hours. The reaction mixture was allowed to cool to room temperature, and added to ice water. The mixture was adjusted to pH 4 by an addition of a 2N aqueous sodium hydroxide solution, and then extracted with 20 ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was .670 subjected to silica gel chromatography to obtain 6.05 g of 1-(2-chloro-3-pyridinyl)-lH-pyrrole-2-carbaldehyde of the formula: H N Ci"1 0 5 1-(2-Chloro-3-pyridinyl)-1H-pyrrole-2-carbaldehyde lH-NMR(DMSO-d 6 , TMS)6(ppm) :6.53(lH,t,J=2Hz) ,7.30 (lH,d,J= 2 Hz) , 7.43(1H,brs),7.59(lH,dd,J=8H,5Hz),8.00(1H,d,J=8Hz), 8.52 (1H,d, J=5Hz) ,9.51(1H,s) Reference Preparation Example 126-(3) 10 To a solution of 6.05 g of 1-(2-chloro-3-pyridinyl) -1H pyrrole-2-carbaldehyde in 20 ml of N,N-dimethylformamide was added 5.72 g of N-bromosuccinimide. The resulting mixture was stirred at room temperature for 1 hour. Water was poured into the reaction mixture, and a deposited precipitate was collected 15 by filtration to obtain 4.22 g of 4-bromo 1-(2-chloro-3-pyridinyl)-1H-pyrrole-2-carbaldehyde of the formula: Br H N Cl O 4-Bromo-1-(2-chloro-3-pyridinyl)-lH-pyrrole-2-carbaldehyde 20 H-NMR (DMSO-d 6 , TMS) 5 (ppm) :7. 42 (1H, d, J=2Hz) ,7. 60 (1H, dd, J=8H, 671 5Hz),7.70(1H,dd,J=2H,1Hz),8.06(lH,dd,J=8H,2Hz),8.

54 (lH,dd, J=5H,2Hz),9.47(1H,d,J=lHz) Reference Preparation Example 126-(4) A solution of 4.43 g of potassium permanganate in 15 mi 5 of water was added dropwise to a mixture of 4.22 g of 4-bromo-1-(2-chloro-3-pyridinyl)-lH-pyrrole-2-carbaldehyde and 30 ml of acetone while the mixture was maintained at 40*C. The resulting mixture was stirred at 40*C for 2 hours. A precipitate was filtered off to obtain a filtrate. The filtrate 10 was adjusted to pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution, and then washed with chloroform two times. The aqueous layer was adjusted to around pH 3 by an addition of 2N hydrochloric acid, and then extracted with ethyl acetate two times. The organic layers were combined, washed 15 successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 3.02 g of 4-bromo-1-(2-chloro-3-pyridinyl)-lH-pyrrole-2-carboxylic acid of the formula: Br OH N CI O 20 N, 4-Bromo-1-(2-chloro-3-pyridinyl)-1H-pyrrole-2-carboxylic acid ,672 'H-NMR(DMSO-dG,TMS) 6(ppm) :7.05 (1H,s) ,7.46(lH,s) ,7.57 (lH,dd, J=BH,4Hz),8.02(lH,d,J=8Hz),8.49(1H,d,J=4Hz),12.70(lH,brs) Reference Preparation Example 126-(5) According to the same manner as that of Reference 5 Preparation Example 71-(5), 4-bromo-l-(2-chloro-3 pyridinyl)-lH-pyrrole-2-carboxylic acid was used in place of 4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxylic acid to obtain 2-[4-bromo-l-(2-chloro-3-pyridinyl)-1H pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1-benzoxazine-4-one of 10 the formula: Br C1 N N

H

3 C CI 2-[4-Bromo--(2-chloro-3-pyridinyl)-H-pyrrol-2-yl)-6 chloro-8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR(DMSO-d 6 ,TMS)6 (ppm) :1.65 (3H, s) ,7.31 (1H, s) ,7.62-7.73 15 (3H,m),7.84(1H,s),8.10(1H,d,J=6Hz),8.57(1H,s) Reference Preparation Example 126-(6) According to the same manner as that of Reference Preparation Example 71-(6), 2-[4-bromo-1-(2-chloro-3 pyridinyl)-lH-pyrrol-2-yl]-6-chloro-8-methyl- 4

H-

3 ,1 20 benzoxazine-4-one was used in place of 2-[4-bromo-1-(3-chloro 2-pyridinyl)-lH-pyrrol-2-yl)-6-chloro-8-methyl-4H-3,1-benzo xazine-4-one to obtain 4-bromo-N-[4-chloro-2- .673 (hydrazinocarbonyl)-6-methylphenyl)-1-(2-chloro-3 pyridinyl)-1H-pyrrole-2-carboxamide of the formula: Br 0H 3 C CI N N H -"NH2 H CI N H N 4-Bromo-N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl] 5 1-(2-chloro-3-pyridinyl)-1H-pyrrole-2-carboxamide 'H-NMR(DMSO-d 6 ,TMS)6(ppm):2.14(3H,s),4.37(2H,brs), 7.28(?H,s),7.40-7.46(2H,m),7.52(1H,dd,J=8H,4Hz),7.95(1H,d, J=8Hz),8.42(lH,d,J=4Hz),9.51(lH,brs),9.82(1H,brs) Reference Preparation Example 127-(l) 10 To a mixture of 0.56 g of 3-amino-4-chloro-2-naphthoic acid and 20 ml of acetic acid was added dropwise 0. 4 g of bromine at room temperature. The resulting mixture was stirred at room temperature for 1 hour. A deposited precipitate was collected by filtration, and the resulting solid was washed successively 15 with acetic acid and ethyl acetate to obtain 0.36 g of 3-amino-7-bromo-4-chloro-2-naphthoic acid of the formula: O OH

H

2 N C1 Br 3-Amino-7-bromo-4-chloro-2-naphthoic acid ,674 H-NMR(DMSO-d 6 ,TMS)6 (ppm):7.70 (1H,d,J=9HZ), 7.81(1H,d,J= 9 HZ), 8.24(1H,s),8.53(lH,s) Reference Preparation Example 127-(2) According to the same manner as that of Reference 5 Preparation Example 46-(1), 3-amino-7-bromo-4-chloro-2 naphthoic acid was used in place of 2-amino-3, 5-dibromobenzoic acid to obtain 7-bromo-2-[3-bromo-l-(3-chloro-2-pyridinyl) 1H-pyrazol-5-yl]-10-chloro-4H-naphtho(2,3-d][1,3]oxazine-4 one of the formula: Br N 0 0 N C1 N CI 10 Br 7-Bromo-2-[3-bromo-l-(3-chloro-2-pyridinyl)-1H-pyrazol-5 yl]-10-chloro-4H-naphtho[2,3-d] [1, 3]oxazine-4-one 'H-NMR(DMSO-d 6 , TMS)6 (ppm):7.56 (1H, s),7.75- 7 .81(1H, m), 7.99(1H,d,J=1OHz),8.14(lH,d,J=1OHz),8.37(lH,d,J=8Hz), 15 8.61-8.68(2H,m),8.85(1H,brs) Reference Preparation Example 128-(1) To a mixture of 0.47 g of 3-amino-2-naphthoic acid and 20 ml of acetic acid was added dropwise 0.8 g of bromine at room temperature. The resulting mixture was stirred at room 20 temperature for 1 hour. A deposited precipitate was collected by filtration, and the resulting solid was washed successively ,67 5 with acetic acid and ethyl acetate to obtain 0.61 g of 3-amino-4,7-dibromo-2-naphthoic acid of the formula: 0 OH

H

2 N Br I Br 3-Amino-4, 7-dibromo-2-naphthoic acid 5 H-NMR(DMSO-d 6 ,TMS)6(ppm) :7.70(1H,dd,J=9,2Hz), 7 .80(lH,d, J=9Hz),8.22(lH,d,J=2Hz),8.57(1H,s) Reference Preparation Example 128-(2) According to the same manner as that of Reference Preparation Example 46-(1), 3,-amino-4,7-dibromo-2-naphthoic 10 acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 7,10-dibromo-2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H pyrazol-5-yll-4H-naphtho[2,3-d][1,3]oxazine-4-one of the formula: Br NI I\ O O 'N C1 N N Br Br 15 7,10-Dibromo-2-[3-bromo-1-(3-chloro-2-pyridinyl)-lH pyrazol-5-yl]-4H-naphtho[2,3-d][1,3]oxazine-4-one 1H-NMR (DMSO-dE, TMS) 6 (ppm) :7. 56 (1H, s) ,7. 76 (1H, dd, J=8Hz, 5Hz) , 7.99(1H,d,J=9Hz),8.14(1H,d,J=9Hz),8.37(1H,d,J=BHz), 676 8.61-8.67(2H,m),8.90(1H,brs) Reference Preparation Example 129-(1) A mixture of 10 g of 2-pyrrolecarbaldehyde, 10 g of 2-fluoropyridine, 24 g of cesium carbonate and 100 ml of 5 N-methylpyrrolidone was stirred at 120 0 C for 1 day. The reaction mixture was allowed to cool to room temperature. Water was poured into the mixture, and the mixture was extracted with ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium 10 chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 7.7 g of 1-(2-pyridinyl)-1H-pyrrole-2-carbaldehyde of the formula: N CHO N 15 1- (2-Pyridinyl) -1H-pyrrole-2-carbaldehyde H-NMR(CDC1 3 ,TMS)5(ppm):6.44(lH,dd,J=4Hz,3Hz), 7

.

2 1(lH,dd, J=4Hz,2Hz),7.30-7.33(1H,m),7.44-7.47(2H,m),7.81- 7

.

8 6(lH,m), 8.53 (1H, dd, J=5Hz, 2Hz) ,9.77 (lH, s) Reference Preparation Example 129-(2) 20 According to the same manner as that of Reference Preparation Example 97- (1), 1- (2-pyridinyl) -1H-pyrrole-2 carbaldehyde was used in place of 3-chloro-2-(2-formyl-1H- .677 pyrrole-1-yl) pyridine to obtain 5-chloro-1- (2-pyridinyl) -1H pyrrole-2-carbaldehyde of the formula: C1 N CHO N 5-Chloro-l-(2-pyridinyl)-1H-pyrrole-2-carbaldehyde 5 'H-NMR(CDCl 3 ,TMS)6(ppm):6.36(1H,d,J=4Hz),7.0 7 (1H,d,J= 4 Hz), 7.38(1H,d,J=8Hz),7.44(lH,dd,J=8Hz,5Hz),7.87-7.91(lH,m), 8.61(lH,d,J=5Hz),9.41(1H,s) Reference Preparation Example 129-(3) According to the same manner as that of Reference 10 Preparation Example 71- (4), 5-chloro-1-(2-pyridinyl) -1H pyrrole-2-carbaldehyde was used in place of 4-bromo-1-(3 chloro-2-pyridinyl)-1H-pyrrole-2-carbaldehyde to obtain 5-chloro-1- (2-pyridinyl) -lH-pyrrole-2-carboxylic acid of the formula: ClN CO2H 15 5-Chloro-l-(2-pyridinyl)-lH-pyrrole-2-carboxylic acid 'H-NMR(DMSO-d 6 ,TMS)6(ppm):6.36(1H,d,J=4Hz),6.98(lH,d,J= 4 Hz), 7.45(1H,d,J=8Hz),7.50-7.53(1H,m),7.97-8.00(1H,m),8.56(1H,d, J=5Hz) ,12. 34 (1H, brs) 678 Reference Preparation Example 129-(4) According to the same manner as that of Reference Preparation Example 71- (5), 5-chloro-1-(2-pyridinyl) -1H pyrrole-2-carboxylic acid was used in place of 4-bromo-1-(3 5 chloro-2-pyridinyl)-1H- pyrrole-2-carboxylic acid to obtain 2-[5-chloro-1-(2-pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8 methyl-4H-3,1-benoxazine-4-one of the formula: N N

H

3 C CI 2-[5-Chloro-l-(2-pyridinyl)-iH-pyrrol-2-yl)-6-chloro-8 10 methyl-4H-3,1-benoxazine-4-one 'H-NMR(CDCl 3 ,TMS)6(ppm):1.70(3H,s),6.38(lH,d,J=4Hz),7.29(lH, d,J=4Hz),7.38(lH,s),7.41-7.49(2H,m),7.91-7.94(2H,m), 8

.

66 (lH, brs) Reference Preparation Example 129-(5) 15 According to the same manner as that of Reference Preparation Example 71-(6), 2-[5-chloro-l-(2-pyridinyl) 1H-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1-benoxazine-4-one was used in place of 2-[4-bromo-1-(3-chloro-2-pyridinyl)-lH pyrrol-2-yl)-6-chloro-8-methyl-4H-3,1-benozxazine-4-one to 20 obtain 5-chloro-N-[4-chloro-2-(hydrazinocarbonyl)-6 methylphenyl -1- (2- pyridinyl) -1H-pyrrole-2-carboxamide of teh formula: 679

H

3 C C1 0 NH -NH2 0 N N H 5-Chloro-N- [4-chloro-2- (hydrazinocarbonyl) -6-methylphenyl) 1- (2-pyridinyl) -1H-pyrrole-2-carboxamide 'H-NMR(DMSO-d 6 ,TMS)6(ppm):2.13(3H,s),4.43(2H,brs), 6

.

4 0(lH,d, 5 J=4Hz),7.11(1H,d,J=4Hz),7.30(1H,d,J=2Hz),7.40-7.47(3H,m), 7.94(1H,td,J=7Hz,2Hz),8.51(1H,dd,J=5Hz,2Hz),9.51(1H,brs), 9.85 (lH, brs) Reference Preparation Example 130 According to the same manner as that of Reference 10 Preparation Example 101, 8-bromo-2-[4-bromo-1-(3-chloro 2-pyridinyl) -1H-pyrrol-2-yl) -6-chloro-4H-3, 1-benoxazine-4 one was used in place of 2-[4-bromo-1-(3-chloro-2-pyridinyl) 1H-pyrrol-2-yl)-6-chloro-8-methyl-4H-3,1-benoxazine-4-one to obtain 4-bromo-N-[6-bromo-4-chloro-2-(N 15 methylhydrazinocarbonyl)phenyl]-1-(3-chlolo-2-pyridinyl)-1H -pyrrole-2-carboxamide of the formula: BrBr C N N H C NNH2 N I N H3C 4-Bromo-N-[6-bromo-4-chloro-2-(N-methylhydrazinocarbonyl) .680 phenyl) -1- (3-chlolo-2-pyridinyl) -lH-pyrrole-2-carboxamide 'H-NMR(CDC13 ,TMS) 6(ppm) :2. 96(1.5H, s) ,3. 15 (1.5H, s) ,4.05(lH, brs),4.49(1H,brs),7.03(1H,d,J=2Hz),7.16(1H,dd,J=7Hz,4Hz), 7.20 (1H,d,J=2Hz) ,7.29-7.34 (1H,m) ,7.47(0.5H,d,J=2Hz), 5 7.53(0.5H,d,J=2Hz) ,7.83-7.79(1H,m) ,8.40-8.43(lH,m), 8.67(0.5H,brs),8.77(0.5H,brs) Reference Preparation Example 131-(1) According to the same manner as that of Reference Preparation Example 129- (1), 2-chloro-3-cyanopyridine was 10 used in place of 2-fluoropyridine to obtain 2-(2-formyl-1H pyrrol-1-yl)-3-cyanopyridine of the formula: N CHO N NC -N 2-(2-Formyl-1H-pyrrol-1-yl)-3-cyanopyridine H-NMR (CDC13 , TMS) 5 (ppm) : 6. 53 (1H, dd, J=4H z, 3H z) , 7. 22 (1H, dd, 15 J=4Hz,2Hz),7.29-7.31(1H,m),7.51(1H,dd,J=8Hz,5Hz),8.12(lH,dd, J=8Hz,2Hz),8.74(1H,dd,J=5Hz,2Hz)9.65(lH,s) Reference Preparation Example 131-(2) According to the same manner as that of Reference Preparation Example 71-(3), 2-(2-formyl-lH-pyrrol-yl)-3 20 cyanopyridine was used in place of 3-chloro-2-(2-formyl-lH pyrrol-1-yl)pyridine to obtain 2-(4-bromo-2-formyl-H pyrrol-1-yl)-3-cyanopyridine of the formula: ,681. Br N CHO NC 1N 2-(4-Bromo-2-formyl-1H-pyrrol-1-yl)-3-cyanopyridine IH-NMR(CDCl 3 ,TMS)5(ppm):7.18(lH,d,J=2Hz),7.29(lH,d,J= 2 Hz), 7.54(1H,dd,J=8Hz,5Hz),8.13(lH,dd,J=8Hz,2Hz),8.74(1H,dd, 5 J=5Hz,2Hz),9.59(1H,s) Reference Preparation Example 131-(3) According to the same manner as that of Reference Preparation Example 71-(4), 2-(4-bromo-2-formyl-lH pyrrol-1-yl)-3-cyanopyridine was used in place of 4-bromo-1 10 (3-chloro-2-pyridinyl)-lH-pyrrole- 2-carbaldehyde to obtain 4-bromo-1-(3-cyano-2-pyridinyl)-lH-pyrrole-2-carboxylic acid of the formula: Br N CO 2 H NC N 4-Bromo-l-(3-cyano-2-pyridinyl)-1H-pyrrole-2-carboxylic 15 acid 'H-NMR(DMSO-d 6 ,TMS)6(ppm):7.10(1H,d,J=2Hz),7.65(1H,d,J= 2 Hz), 7.75(1H,dd,J=8Hz,5Hz),8.55(1H,dd,J=8Hz,2Hz),8.82(1H,dd,J=5H z,2Hz) Reference Preparation Example 131-(4) .682 According to the same manner as that of Reference Preparation Example 71- (5), 4-bromo-1-(3-cyano-2-pyridinyl) 1H-pyrrole-2-carboxylic acid and 2-amino-3,5-dibromobenzoic acid were used in place of 4-bromo-1-(3-chloro-2-pyridinyl)-' 5 1H-pyrrole-2-carboxylic acid and 2-amino-5-chloro-3 methylbenozoic acid respectively to obtain 6,8-dibromo-2-[4 bromo-1-(3-cyano-2-pyridinyl)-1H-pyrrol-2-yl]-4H-3,1-benzox azine-4-one of the formula: Br 0 0 N NC N Br Br 10 6,8-Dibromo-2-[4-bromo-1-(3-cyano-2-pyridinyl)-1H-pyrrol-2 -yl)-4H-3,1-benoxazine-4-one 1 H-NMR(DMSO-d 6 ,TMS)6(ppm):7.39(1H,d,J=2Hz),7.77(1H,dd,J=8Hz, 5Hz),7.81(lH,d,J=2Hz),8.14(1H,d,J=2Hz),8.21(lH,d,J= 2 Hz), 8.58(1H,dd,J=8Hz,2Hz),8.83(1H,dd,J=5Hz,2Hz) 15 Reference Preparation Example 132-(1) According to the same manner as that of Reference Preparation Example 129-(1), 2-chloro-3 trifluoromethylpyridine was used in place of 2-f luoropyridine to obtain 1-(3-trifluoromethyl-2-pyridinyl)-1H-pyrrole-2 20 carbaldehyde of the formula: 683 F N CHO F N F N 1-(3-Trifluoromethyl-2-pyridinyl)-1H-pyrrole-2 carbaldehyde 1 H-NMR(CDCl 3 ,TMS)6(ppm):6.47(1H,dd,J=4Hz,3Hz),7.12- 7 .14( 2 H, 5 m),7.59(1H,dd,J=8Hz,5Hz),8.18(1H,d,J=8Hz),8.75(1H,d,J=5Hz), 9. 54 (1H, d, J=lHz) Reference Preparation Example 132-(2) According to the same manner as that of Reference Preparation Example 71-(3), 1-(3-trifluoromethyl-2 10 pyridinyl)-1H-pyrrole-2-carbaldehyde was used in place of 3-chloro-2-(2-formyl-lH-pyrrol-1-yl)pyridine to obtain 4-bromo-l-(3-trifluoromethyl-2-pyridinyl)-1H-pyrrole-2 carbaldehyde of the formula: Br F N CHO F N 15 4-Bromo-l-(3-trifluoromethyl-2-pyridinyl)-H-pyrrole-2 carbaldehyde 1 H-NMR(CDCl 3 ,TMS)6(ppm):7.11(2H,s),7.62(li,dd,J=8Hz,5Hz), 8.18(1H,d,J=8Hz),8.74(1H,d,J=5Hz),9.47(lH,s) Reference Preparation Example 132-(3) -684 According to the same manner as that of Reference Preparation Example 71-(4), 4-bromo-1-(3-trifluoromethyl- 2 pyridinyl)-1H-pyrrole-2- carbaldehyde was used in place of 4-bromo-l-(3-chloro-2-pyridinyl)-lH-pyrrole-2-carbaldehyde 5 to obtain 4-bromo-1- (3-trifluoromethyl-2-pyridinyl) -1H pyrrole-2-carboxylic acid of the formula: Br F N CO 2 H F N 4-Bromo-1-(3-trifluoromethyl-2-pyridinyl)-lH-pyrrole-2 carboxylic acid 10 H-NMR(DMSO-d 6 ,TMS)5(ppm):7.02(lH,d,J=2Hz),7.56(lH,d,J= 2 Hz), 7.80(lH,dd,J=7Hz,5Hz),8.42(1H,d,J=7Hz),8.82(1H,d,J=5Hz),1 2 . 66 (1H,brs) Reference Preparation Example 132-(4) According to the same manner as that of Reference 15 Preparation Example 71-(5), 4-bromo-1-(3-trifluoromethyl 2-pyridinyl)-lH-pyrrole-2- carboxylic acid and 2-amino-3,5 dibromobenzoic acid were used in place of 4-bromo-1- (3-chloro 2-pyridinyl)-lH-pyrrole-2-carboxylic acid and 2-amino-5 chloro-3-methylbenzoic acid respectively to obtain 20 6,8-dibromo-2-[4-bromo-l-(3-trifluoromethyl-2-pyridinyl) 1H-pyrrol-2-yl]-4H-3,1-benzoxazine-4-one of the formula: .685 Br 0 0

N

1

F

3 C *" "','

-

Br Br 6, 8-Dibromo-2- [4-bromo-1- (3-trifluoromethyl-2-pyridinyl) 1H-pyrrol-2-yl ]-4H-3, 1-benzoxazine-4-one 'H-NMR(DMSO-d 6 ,TMS)6(ppm):7.34(lH,s),7.71(lH,s), 7 .8 3 (l,dd, 5 J=8Hz,5Hz),8.10(lH,d,J=2Hz),8.19(lH,d,J=2Hz),8.48(lH,d, J=8Hz),8.84(lH,d,J=5Hz) Reference Preparation Example 133-(1) According to the same manner as that of Reference Preparation Example 71- (4) , 1-,(3-chloro-2-pyridinyl) -5-iodo 10 1H-pyrrole-2-carbaldehyde was used in place of 4-bromo-l-(3 chloro-2-pyridinyl)-lH-pyrrole-2-carbaldehyde to obtain 1-(3-chloro-2-pyridinyl)-5-iodo-lH-pyrrole-2-carboxylic acid of the formula: SN CO2H 15 1- (3-Chloro-2-pyridinyl) -5-iodo-1H-pyrrole-2-carboxylic acid 'H-NMR(DMSO-d 6 ,TMS)6(ppm):6.63(lH,d,J=4Hz),6.97(lH,d,J= 4 Hz), 7.62(lH,dd,J=8Hz,5Hz),8.20(lH,d,J=8Hz),8.56(lH,d,J=5Hz), 12.43(lH,brs) ,686 Reference Preparation Example 133-(2) According to the same manner as that of Reference Preparation Example 71-(5), 1-(3-chloro-2-pyridinyl)-5-iodo 1H-pyrrole-2-carboxylic acid was used in place of 5 4-bromo-1- (3-chloro-2-pyridinyl) -lH-pyrrole- 2-carboxylic acid to obtain 6-chloro-2-[1-(3-chloro-2-pyridinyl)-5-iodo 1H-pyrrol-2-yl) -8-methyl-4H-3, 1-benzoxazine-4-one of the formula: Ct N N / C 1 N N HCC -N

H

3 C C1 10 6-Chloro-2-[1-(3-chloro-2-pyridinyl)-5-iodo-1H-pyrrol 2-yl)-8-methyl-4H-3,1-benzoxazine-4-one 1H-NMR(DMSO-d,,TMS)5(ppm):1.65(3H,s),6.82(1H,d,J= 3 Hz), 7.23(lH,d,J=3Hz),7.67(H,s),7.71(1H,dd,J=BHz,5Hz), 7.81(lH,s),8.32(1H,d,J=8Hz),8.65(1H,d,J=5Hz) 15 Reference Preparation Example 133-(3) According to the same manner as that of Reference Preparation Example 71-(6), 6-chloro-2-[I-(3-chloro-2 pyridinyl) -5-iodo-1H-pyrrol-2-yl) -B-methyl-4H-3, 1 benzoxazine-4-one was used in place of 2-[4-bromo-1- (3-chloro 20 2-pyridinyl)-H-pyrrol-2-yl)-6-chloro-8-methyl- 4 H-3, 1 benzoxazine-4-one to obtain N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl)-1-(3-chlo 687 ro-2-pyridinyl) -5-iodo-lH-pyrrole-2-carboxamide of the formula:

H

3 C CI N N H NH2 CI O N N H N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl)-1-(3 5 chloro-2-pyridinyl)-5-iodo-1H-pyrrole-2-carboxamide 'H-NMR(CDCl 3 ,TMS)5(ppm):2.16(3H,s),4.02(2H,brs),6.66(lH,s), 7.05(lH,s),7.19(lH,s),7.24(lH,s),7.37(lH,dd,J=8Hz,5Hz), 7.50(lH,brs),7.86(lH,d,J=8Hz),8.49(lH,d,J=5Hz),9.28(1H,brs) Reference Preparation Example 134-(1) 10 A mixture of 1.51 g of 2-amino-3-methylbenzoic acid, 1.0 g of acetic anhydride and 20 ml of tetrahydrofuran was stirred at 80 0 C for 13 hours. The reaction mixture was allowed to cool to room temperature, poured into water, and extracted with ethyl acetate two times. The organic layers were combined, 15 washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was washed with ethyl acetate to obtain 0.72 g of 2-acetylamino-3 methylbenzoic acid of the formula: 688 0 OH H

H

3 C N 0)3z

H

3 C. 2-Acetylamino-3-methylbenzoic acid 1 H-NMR(DMSO-d 6 ,TMS)6(ppm) :2.00(3H,s) ,2.19(3H,s) ,7.21(1H,t, J=8Hz),7.41(lH,d,J=8Hz),7.58(lH,d,J=8Hz),9.47(lH,brs) 5 Reference Preparation Example 134-(2) To a mixture of 0.72 g of 2-acetylamino-3-methylbenzoic acid and 8 ml of concentrated sulfuric acid was added dropwise 1.6 g of fuming nitric acid at room temperature. The resulting mixture was stirred at room temperature for 2 hours. The 10 reaction mixture was poured into ice water. A deposited precipitate was collected by filtration to obtain 0.45 g of 2-acetylamino-3-methyl-5-nitrobenzoic acid of the formula: O OH H

H

3 C N 0

H

3 C NO2 2-Acetylamino-3-methyl-5-nitrobenzoic acid 15 'H-NMR(DMSO-d,,TMS)6(ppm):2.06(3H,s),2.34(3H,s),8.

3 1( 2 H,s), 9.93 (1H,brs) Reference Preparation Example 134-(3) A mixture of 0.45 g of 2-acetylamino-3-methyl-5 nitrobenzoic acid, 0.45 g of potassium hydroxide, 5 ml of 20 methanol and 20 ml of water was heated to reflux at 80*C for 2 hours. The reaction mixture was allowed to cool to room ,689 temperature, and water was poured into the mixture. The mixture was adjusted to pH 3 by an addition of 2N hydrochloric acid. A deposited precipitate was collected by filtration to obtain 0.28 g of 2-amino-3-methyl-5-nitroben zoic acid of the formula: O OH

H

2 N 5

H

3 C

NO

2 2-Amino-3-methyl-5-nitrobenzoic acid IH-NMR(DMSO-d 6 ,TMS)b(ppm) :2.19(3H,s) ,7.99(lH,s) ,8.56(1H,s) Reference Preparation Example 134-(4) According to the same manner as that of Reference 10 Preparation Example 46-(1), 2-amino-3-methyl-5-nitrobenzoic acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain 2-[3-bromo-1-(3-chloro-2-pyridinyl)-lH-pyrazol-5 yl]-8-methyl-6-nitro-4H-3,1-benzoxazine-4-one of the formula: Br N.. 0 0 CIN %N 15

H

3 C NO 2 2-[3-Bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-yl]-8 methyl-6-nitro-4H-3,1-benzoxazine-4-one 'H-NMR(DMSO-d 6 ,TMS)6(ppm):1.81(3H,s),7.64(1H,s), 7

.

7 9 (lH,dd, J=BHz,4Hz),8.38(1H,d,J=8Hz),8.48(lH,s),8.55(1H,s), 8

.

64 (lH,d, -690 J=4Hz) Reference Preparation Example 135-(l) According to the same manner as that of Reference Preparation Example 129-(1), 2-chloro-3-nitropyridine was 5 used in place of 2-fluoropyridine to obtain 1-(3-nitro-2 pyridinyl)-1H-pyrrole-2-carbaldehyde of the formula: N CHO 0 2 N t 1-(3-Nitro-2-pyridinyl)-1H-pyrrole-2-carbaldehyde lH-NMR(CDCl 3 ,TMS)5(ppm):6.54(.1H,dd,J=4Hz,3Hz),7.18(1H,dd, 10 J=4Hz,2Hz),7.34-7.35(1H,m),7.60(1H,dd,J=8Hz,5Hz),8.51(1H, dd,J=8Hz,2Hz),8.75(lH,dd,J=5Hz,2Hz),9.48(1H,d,J=1Hz) Reference Preparation Example 135-(2) According to the same manner as that of Reference Preparation Example 71-(3), 1-(3-nitro-2-pyridinyl)-1H 15 pyrrole-2-carbaldehyde was used in place of 3-chloro-2-(2 formyl-lH-pyrrol-1-yl)pyridine to obtain 4-bromo-1-(3 nitro-2-pyridinyl) -lH-pyrrole-2-carbaldehyde of the formula: Br N CHO 0 2 N N 4-Bromo-1-(3-nitro-2-pyridinyl)-lH-pyrrole-2-carbaldehyde .691 H-NMR(CDC1 3 ,TMS)6(ppm):7.14(1H,d,J=2Hz),7.33(1H,d,J= 2 Hz), 7.63(1H,dd,J=8Hz,5Hz),8.53(1H,dd,J=8Hz,2Hz),8.75(1H,dd, J=5Hz,2Hz), 9.42 (1H, s) Reference Preparation Example 135-(3) 5 According to the same manner as that of Reference Preparation Example 71- (4), 4-bromo-1- (3-nitro-2-pyridinyl) 1H-pyrrole-2-carbaldehyde was used in place of 4-bromo-1-(3 chloro-2-pyridinyl)-1H-pyrrole-2- carbaldehyde to obtain 4-bromo-1- (3-nitro-2-pyridinyl) -1H-pyrrole-2- carboxylic 10 acid of the formula: Br N CO 2 H 0 2 N N 4-Bromo-1-(3-nitro-2-pyridinyl)-1H-pyrrole-2-carboxylic acid lH-NMR(DMSO-d,TMS)6(ppm):7.05(H,d,J=2Hz),7.60(lH,d,J= 2 Hz), 15 7.84(1H,dd,J=8Hz,5Hz),8.68(1H,d,J=8Hz,2Hz),8.84(lH,d,J= 5 Hz, 2Hz) Reference Preparation Example 135-(4) According to the same manner as that of Reference Preparation Example 71- (5), 4-bromo-1-(3-nitro-2-pyridinyl) 20 1H-pyrrole-2-carboxylic acid and 2-amino-3,5-dibromobenzoic acid were used in place of 4-bromo-1-(3-chloro-2-pyridinyl) 1H-pyrrole-2-carboxylic acid and 2-amino-5-chloro-3- .692 methylbenzoic acid respectively to obtain 6,8-dibromo-2 [4-bromo-1-(3-nitro-2-pyridinyl)-1H-pyrrol-2-yl]- 4

H-

3 ,1 benzoxazine-4-one of the formula: Br 00 N 0 2 N tjNB B Br Br 5 6,8-Dibromo-2-[4-bromo-l-(3-nitro-2-pyridinyl)-lH-pyrrol-2 -yl]-4H-3,1-benzoxazine-4-one 'H-NMR(DMSO-d 6 ,TMS)6(ppm):7.38(lH,d,J=2Hz),7.80(lH,d,J=2Hz), 7.92(lH,dd,J=8Hz,5Hz),8.1l(lH,d,J=2Hz),8.26(lH,d,J=2Hz), 8.84 (lH,d,J=8Hz),8.65(lH,d,J=5Hz) 10 Reference Preparation Example 136-(1) According to the same manner as that of Reference Preparation Example 129-(l), 3-bromo-2-chloropyridine was used in place of 2-fluoropyridine to obtain 1-(3-bromo-2 pyridinyl)-1H-pyrrole-2-carbaldehyde of the formula: N CHO Br N 15 1-(3-Bromo-2-pyridinyl)-1H-pyrrole-2-carbaldehyde IH-NMR(CDCl 3 ,TMS)6(ppm):6.48(1H,dd,J=4Hz,3Hz),7.10-7.17 (2H,m),7.31(lH,dd,J=8Hz,5Hz),8.05(lH,dd,J=8Hz,2Hz),8.51(lH, dd,J=5Hz,2Hz),9.57(lH,s) .693 Reference Preparation Example 136-(2) According to the same manner as that of Reference Preparation Example 71-(3), 1-(3-bromo-2-pyridinyl)-1H 5 pyrrole-2-carbaldehyde was used in place of 3-chloro-2 (2-formyl-1H-pyrrol-1-yl)pyridine to obtain 4-bromo-1-(3 bromo-2-pyridinyl) -1H-pyrrole-2-carbaldehyde of the formula: Br N CHO Br N 4-Bromo-1-(3-bromo-2-pyridinyl)-1H-pyrrole-2-carbaldehyde 10 lH-NMR(CDCla,TMS)&(ppm):7.1l-7.14(2H,m),7.33(lH,dd,J= 8 Hz, 5Hz),8.06(lH,dd,J=8Hz,2Hz),8.50(lH,dd,J=5Hz,2Hz),9.50(lH,d, J=lHz) Reference Preparation Example 136-(3) According to the same manner as that of Reference 15 Preparation Example 71- (4), 4-bromo-1-(3-bromo-2-pyridinyl) 1H-pyrrole-2-carbaldehyde was used in place of 4-bromo-1-(3 chloro-2-pyridinyl)-lH- pyrrole-2-carbaldehyde to obtain 4-bromo-1-(3-bromo-2-pyridinyl)-lH- pyrrole-2-carboxylic acid of the formula: 694 Br N CO 2 H Br- N 4-Bromo-1- (3-bromo-2-pyridinyl) -1H-pyrrole-2-carboxylic acid 'H-NMR (DMSO-d , TMS) (ppm) :7.01 (1H, s) ,7.48-7.51 (2H,m) 8.28 5 (1H,d,J=8Hz),8.52(1H,d,J=5Hz),12.67(1H,brs) Reference Preparation Example 136-(4) According to the same manner as that of Reference Preparation Example 71- (5), 4-bromo-1- (3-bromo-2-pyridinyl) 1H-pyrrole-2-carboxylic acid and 2-amino-3, 5-dibromobenzoic 10 acid were used in place of 4-bromo-1- (3-chloro-2-pyridinyl) 1H-pyrrole-2-carboxylic acid and 2-amino-5-chloro-3 methylbenzoic acid respectively to obtain 6,8-dibromo-2-[4 bromo-1- (3-bromo-2-pyridinyl) -lH-pyrrol-2-yl] -4H-3, 1 benzoxazine-4-one of the formula: Br N 15 Br Br 6,8-Dibromo-2-[4-bromo-l-(3-bromo-2-pyridinyl)-1H-pyrrol 2-yl]-4H-3,1-benzoxazine-4-one lH-NMR(DMSO-d 6 ,TMS)5(ppm):7.33(lH,s),7.53(lH,dd,J=BHz,5Hz), 7.72 (1H, s) ,8. 12 (1H, d, J=2Hz), 8. 27 (1H, d, J=2Hz) ,8. 36 (1H, d, -695 J=8Hz),8.57(lH,d,J=5Hz) Reference Preparation Example 137-(1) A mixture of 2.0 g of 2-pyrrolecarbaldehyde, 3.0 g of 3, 4-dichloropyridine, 8.0 g of cesium carbonate and 30 ml of' 5 N-methylpyrrolidone was stirred at 120 0 C for 25 hours. The reaction mixture was allowed to cool room temperature, and water was poured into the mixture. The mixture was extracted with ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium 10 chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 2.95 g of 1-(3-chloro-4-pridinyl)-1H-pyrrole-2-carbaldehyde of the formula: 71 H CI O 15 N 1-(3-Chloro-4-pridinyl)-lH-pyrrole-2-carbaldehyde 'H-NMR (DMSO-d 6 , TMS) 5 (ppm) :6. 55 (1H, dd, J=4Hz, 3Hz), 7. 33 (1H, dd, J=4Hz,2Hz),7.44(lH,ddd,J=3Hz,2Hz,1Hz),7.60(lH,d,J=5Hz), 8.66(lH,d,J=5Hz),8.83(1H,s),9.52(lH,d,J=lHz) 20 Reference Preparation Example 137-(2) To a solution of 2.95 g of 1-(3-chloro-4-pyridinyl)-1H pyrrole-2-carbaldehyde in 20 ml of N,N-dimethylformamide was 696 added 2.66 g of N-bromosuccinimide. The resulting mixture was stirred at room temperature for 10 hours. Water was poured into the reaction mixture, and a deposited precipitate was collected by filtration to obtain 1.2 g of 5 4-bromo-l-(3-chloro-4-pyridinyl)-1H-pyrrole-2-carbaldehyde of the formula: Br H N N 4-Bromno-1-(3-chloro-4-pyridinyl)-1H-pyrrole-2-carbaldehyde 1H-NMR(DMSO-d 6 , TMS) 6 (ppm) :7. 44-7.46 (1H,m), 7. 66 (1H, d, J=5Hz) , 10 7.69-7.72(1H,m),8.68(lH,d,J=5Hz),8.85(1H,s),9.47(lH,s) Reference Preparation Example 137-(3) A solution of 2.0 g of potassium permanganate in 10 ml of water was added dropwise to a mixture of 1.2 g of 4-bromo-l (3-chloro-4-pyridinyl)-1H-pyrrole-2-carbaldehyde and 30 ml of 15 acetone while the mixture was maintained at 40 0 C. The resulting mixture was stirred at 60 0 C for 1 hour. A precipitate was filtered off to obtain a filtrate. The filtrate was adjusted to pH 10-12 by an addition of a 2N aqueous sodium hydroxide solution, and then washed with chloroform two times. The 20 aqueous layer was adjusted to around pH 3 by an addition of 2N hydrochloric acid, and then extracted with ethyl acetate two times. The organic layers were combined, washed successively -697 with water and an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 0.43 g of 4-bromo-1-(3-chloro- 4 pyridinyl)-1H-pyrrole-2-carboxylic acid of the formula: Br OH N C1 0 5 N 4-Bromo-1-(3-chloro-4-pyridinyl)-1H-pyrrole-2-carboxylic acid H-NMR(DMSO-d 6 ,TMS) 6 (ppm) : 7.07 (1H,d, J=2Hz) , 7.47 (1H,d, J=2Hz), 7.63(1H,d,J=5Hz),8.65(1H,d,J=5Hz),8.81(lH,s) Reference Preparation Example 137-(4) 10 According to the same manner as that of Reference Preparation Example 71-(5), 4-bromo-1-(3-chloro-4 pyridinyl)-1H-pyrrole-2-carboxylic acid was used in place of 4-bromo-1-(3-chloro-2-pyridinyl)- 1H-pyrrole-2-carboxylic acid to obtain 2-(4-bromo-1-(3-chloro-4-pyridinyl)-1H 15 pyrrol-2-yll-6-chloro-8-methyl-4H-3,1- benzoxazine-4 -one of the formula: Br N CI N N H 3 C CI 2-[4-Bromo-l-(3-chloro-4-pyridinyl)-1H-pyrrol-2-yl]-6 chloro-8-methyl-4H-3,1-benzoxazine-4-one 698 'H-NMR(DMSO-d 6 ,TMS) 6 (ppm) :1. 63 (3H, s) , 7.33 (lH,d, J=2Hz) , 7 .68 7.74 (3H,m),7.85(lH,d,J=2Hz),8.73(lH,d, J=5Hz),8.91(lH,s) Reference Preparation Example 137-(5) According to the same manner as that of Reference 5 Preparation Example 71-(6), 2-[4-bromo-1-(3-chloro-4 pyridinyl)-lH-pyrrol-2-yl]-6-chloro-8-methyl-4H-3,1 benzoxazine-4-one was used in place of 2-[4-bromo-1-(3 chloro-2-pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8-methyl-4H-3, 1-benzoxazine-4-one to obtain 4-bromo-N-[4-chloro-2 10 (hydrazinocarbonyl)-6-methylphenyl)-1-(3-chloro-4-pyridinyl )-lH-pyrrole-2-carboxamide of the formula:

H

3 C C1 Br / / N N H -NH2 CI O N H N 4-Bromo-N-[4-chloro-2-(hydrazinocarbonyl)-6-methylphenyl] 1- (3-chloro-4-pyridinyl) -1H-pyrrole-2-carboxamide 15 H-NMR(DMSO-d 6 ,TMS)5(ppm) :2.15(3H,s),4.39(2H,brs),7.2 7

-

7

.

3 1 (2H,m),7.42-7.46(2H,m),7.56(1H,d,J=5Hz),8.60(lH,d,J=5Hz), 8.72(lH,s),9.54(lH,brs),9.87(lH,brs) Reference Preparation Example 138-(1) According to the same manner as that of Reference 20 Preparation Example 46- (1), 2-amino-5-chloro-benzoic acid was used in place of 2-amino-3,5-dibromobenzoic acid to obtain .699 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-yl]-6 chloro-4H-3,1- benzoxazine-4-one of the formula: Br N O CIN / C N C1 2- [3-Bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-yl]-6 5 chloro-4H-3, 1-benzoxazine-4-one H-NMR (DMSO-d,, TMS) 6 (ppm) :7. 01 (1H, d, J=9Hz) ,7.53 (1H, s) , 7

.

78 (1H,dd,J=8Hz,5Hz),7.88(1H,dd,J=9Hz,3Hz),8.06(1H,d,J=3Hz), 8.32(1H,dd,J=8Hz,1Hz),8.60(1H,dd,J=5Hz,1Hz). Reference Preparation Example,139 10 According to the same manner as that of Reference Preparation Example 84, 2-[3-bromo-1-(3-chloro-2-pyridinyl) 1H-pyrazol-5-yl) -6- chloro-4H-3, 1-benzoxazine-4-one was used in place of 2-[3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazol 5-yl]-6- chloro-8-methyl-4H-3,1-benoxazine-4-one to obtain 15 3-bromo-N-[4-chloro-2-(N-methylhydrazinocarbonyl)phenyl]-1 -(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide of the formula: Br OC H C1 0 N

H

3 C 3-Bromo-N-[4-chloro-2-(N-methylhydrazinocarbonyl)phenyl]- 700 1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide lH-NMR(DMSO-d 6 ,TMS)5(ppm):2.88(0.6H,s),3.10(2.4H,s), 4

.

7 1 (1.6H,s),5.01(0.4H,s),7.29-7.34(1.OH,brm),7.38-7.52(3.OH,m), 7.65(1.OH,dd,J=8Hz,5Hz),8.22(1.0H,dd,J=8Hz,2Hz),8.52(1.OH, 5 dd,J=5Hz,2Hz),10.40-10.50(1.OH,brm). Reference Preparation Example 140 According to the same manner as that of Reference Preparation Example 88, 2-[3-bromo-l-(3-chloro-2-pyridinyl) 1H-pyrazol-5-yl]-6-chloro-4H-3,1-benzoxazine-4-one was used 10 in place of 2-[3-bromo-l-(3-chloro-2-pyridinyl)-1H-pyrazol 5-yl]-6-. chloro-8-methyl-4H-3,1-benzoxazine-4-one to obtain 3-bromo-N-[4-chloro-2-(N,N'-dimethylhydrazinocarbonyl) phenyl] -1- (3-chloro-2-pyridinyl) -lH-pyrazole-5-carboxamide of the formula: Br O / C1 N, N"' CH 3 N H IN C N H 3 C 15 3-Bromo-N-[4-chloro-2-(N,N'-dimethylhydrazinocarbonyl) phenyl)-1-(3-chloro-2-pyridinyl)-lH-pyrazole-5-carboxamide 1 H-NMR(CDCl 3 ,TMS)6(ppm):2.69(3H,brs),3.28 (3H,s),6.92(1H,s), 7.30-7.46(3H,m),7.91(lH,dd,J=8Hz,2Hz),8.17(1H,d,J=9Hz),8.49 20 (lH,dd,J=5Hz,2Hz),10.29(lH,brs). Reference Preparation Example 141-(l) According to the same manner as that of Reference ,701 Preparation Example Preparation Example 100- (1) , 2- (2-f ormyl 1H-pyrrol-1-yl)pyridine was used in place of 3-chloro-2-(2 formyl-1H-pyrrol-1-yl)pyridine to obtain 4,5-dichloro-l-(2 pyridinyl) -lH-pyrrole-2-carbaldehyde of the formula: CI CI N CHO 5 N and 3,5-dichloro-l-(2-pyridinyl)-1H-pyrrole-2-carbaldehyde of the formula: CI CI N CHO N 4, 5-Dichloro-l- (2-pyridinyl) -lH-pyrrole-2-carbaldehyde 10 1 H-NMR(CDCl 3 ,TMS)6(ppm) :7.08(1H,s),7.38-7.41(lH,m),7.47 7.50(1H,m),7.91-7.95(1H,m),8.63-8.65(1H,m),9.40(1H,s) 3,5-Dichloro-1-(2-pyridinyl)-lH-pyrrole-2-carbaldehyde 1 H-NMR(CDCl 3 , TMS) 6 (ppm) :6. 35 (1H, s) ,7. 33-7. 36 (1H,m), 7.

45 15 7.48 (1H,m) ,7.89-7.93 (1H,m) ,8.61-8.62 (1H,m) ,9.64 (1H, s) Reference Preparation Example 141-(2) According to the same manner as that of Reference Preparation Example 71- (4), 4,5-dichloro-1- (2-pyridinyl) -lH pyrrole-2-carbaldehyde was used in place of 4-bromo-1-(3- .702 chloro-2-pyridinyl)-lH-pyrrole-2-carbaldehyde to obtain 4, 5-dichloro-l- (2-pyridinyl) -1H-pyrrole-2-carboxylic acid of the formula: CI Cl N CO 2 H N 5 4,5-Dichloro-1-(2-pyridinyl)-lH-pyrrole-2-carboxylic acid 1 H-NMR(DMSO-d 6 ,TMS)6(ppm):7.11(1H,s),7.56- 7 .5 8

(

2 H,m),8.0 3 (1H,td,J=8Hz,2Hz),8.58(1H,dd,J=4Hz,2Hz) Reference Preparation Example 141-(3) According to the same manner as that of Reference 10 Preparation Example 71-(5), 4, 5-dichloro-1-(2-pyridinyl) 1H-pyrrole-2-carboxylic acid was used in place of 4-bromo-l (3-chloro-2-pyridinyl)-lH- pyrrole-2-carboxylic acid to obtain 6-chloro-2-(4,5-dichloro-1-(2-pyridinyl)-lH-pyrrol 2-yl]-8-methyl-4H-3,1-benzoxazine- 4-one of the formula: C1 C1 O O C N N 15

H

3 C Cl 6-Chloro-2- [4, 5-dichloro-l- (2-pyridinyl) -1H-pyrrol-2-yl] 8-methyl-4H-3,1-benzoxazine-4-one 'H-NMR(DMSO-d 6 ,TMS)5(ppm):2.07(3H,s),7.35(1H,s), 7 .62- 7 .67 .703 (3H,m),7.81(lH,s),8.11(1H,t,J=8Hz),8.65(1H,d,J=5Hz) Reference Preparation Example 141-(4) According to the same manner as that of Reference Preparation, Example 71- (6), 6-chloro-2-[4, 5-dichloro-1 5 (2-pyridinyl)-1H-pyrrol-2-yl]-8-methyl-4H-3,1-benzoxazine-4 -one was used in place of 2- [4-bromo-l- (3-chloro-2-pyridinyl) 1H-pyrrol-2-yl]-6- chloro-8-methyl-4H-3,1-benzoxazine-4-one to obtain 4,5-dichloro-N-[4-chloro-2-(hydrazinocarbonyl)-6 methylphenyl -- 1- (2-pyridinyl) -lH-pyrrole-2-carboxamide of 10 the formula:

H

3 C C1 NN CI N H .NH2 O N N H 4, 5-Dichloro-N- [4-chloro-2- (hydrazinocarbonyl) -6 methylphenyl)-1-(2-pyridinyl)-1H-pyrrole-2-carboxamide 'H-NMR(CDC1 3 ,TMS)8 (ppm) :2.16 (3H, s) , 7.01(lH, s) , 7.25 (2H, s), 15 7.36-7.41(2H,m),7.87(1H,td,J=8Hz,2Hz),7.95(1H,brs), 8.55-8.57(lH,m),9.42(lH,brs) Reference Preparation Example 142-(l) According to the same manner as that of Reference Preparation Example 71-(4), 3,5-dichloro-l-(2-pyridinyl)-1H 20 pyrrole-2-carbaldehyde was used in place of 4-bromo-l-(3 chloro-2-pyridinyl)-1H-pyrrole- 2-carbaldehyde to obtain 704 3, 5-dichloro-1- (2-pyridinyl) -1H-pyrrole-2-carboxylic acid of the formula: CI CI N

CO

2 H N 3,5-Dichloro-1-(2-pyridinyl)-1H-pyrrole-2-carboxylic acid 5 'H-NMR(DMSO-d 6 ,TMS)6(ppm):6.64(1H,s),7.53- 7 .5 7

(

2 H,m), 8. 02 (1H, td, J=8Hz, 2Hz) ,8. 55-8 .57 (1H, m) Reference Preparation Example 142-(2) According to the same manner as that of Reference Preparation Example 71-(5), 3,5-dichloro-1-(2-pyridinyl) 10 1H-pyrrole-2-carboxylic acid was used in place of 4-bromo-1 (3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxylic acid to obtain 6-chloro-2-[3,5-dichloro-1-(2-pyridinyl)-lH-pyrrol 2-yl]-8-methyl-4H-3,1-benzoxazine-4-one of the formula: C 0 0 N 6I N

H

3 C 15 6-Chloro-2-[3,5-dichloro-1-(2-pyridinyl)-1H-pyrrol-2-yl] 8-methyl-4H-3,1-benzoxazine-4-one 1 H-NMR(DMSO-d 6 ,TMS)6(ppm):1.82(3H,s),6.

97 (lH,s), 7 .60-7.

7 0 (3H,m),7.81-7.83(1H,m),8.04-8.12(1H,m),8.58(1H,d,J=6Hz) -705 Reference Preparation Example 142- (3) According to the same manner as that of Reference Preparation Example 71-(6), 6-chloro-2-(3,5-dichloro-1-(2 pyridinyl)-1H-pyrrol-2-yl]-8-methyl- 4

H-

3 ,1-benzoxazine-4 5 one was used in place of 2-[4-bromo-1-(3-chloro-2-pyridinyl) 1H-pyrrol-2-yl]-6-chloro-8-methyl- 4H-3,1-benzoxazine-4-one to obtain 3,5-dichloro-N-[4-chloro-2-(hydrazinocarbonyl)-6 methylphenyl]-1-(2-pyridinyl)-1H- pyrrole-2-carboxamide of the formula: C1 H 3 C CI N N N HH 10 3,5-Dchloro-N-[4-chloro-2-(hydrazinocarbonyl)-6 methylphenyl]-1-(2-pyridinyl)-1H-pyrrole-2-carboxamide 1 H-NMR(CDCl 3 ,TMS)&(ppm):2.14(3H,s),6.26(1H,s), 7 .20- 7

.

2 3 (2H, s), 7.28-7.34 (2H,m), 7.61-7.65(1H,m), 7.76-7.81(1H,,m) , 15 8.49(1H,brs),8.79(1H,brs) Reference Preparation Example 143-(1) To a solution of 3.0 g of 3-chloro-2-(4-bromo-2 formyl-lH-pyrrol-1-yl)-pyridine in 30 ml of tetrahydrofuran was added 1.5 g of N-chlorosuccinimide. The resulting mixture 20 was stirred at room temperature for 2 days. Water was poured into the reaction mixture, and the mixture was extracted with .706 ethyl acetate two times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel' 5 column chromatography to obtain 2.5 g of 4-bromo-5-chloro-1 (3-chloro-2-pyridinyl)-1H-pyrrole-2-carbaldehyde of the formula: Br CI N CHO C' N 4-Bromo-5-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2 10 carbaldehyde 'H-NMR(CDCl 3 ,TMS)5(ppm):7.12(1H,s),7.47(lH,dd,J=8Hz,5Hz), 7.94(1H,dd,J=8Hz,2Hz),8.53(1H,dd,J=5Hz,2Hz),9.38(1H,s) Reference Preparation Example 143-(2) According to the same manner as that of Reference 15 Preparation Example 71-(4), 4-bromo-5-chloro-1-(3-chloro- 2 pyridinyl)-lH-pyrrole-2-carbaldehyde was used in place of 4-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carbaldehyde to obtain 4-bromo-5-chloro-1-(3-chloro-2-pyridinyl)-1H pyrrole-2-carboxylic acid of the formula: * 707 Br CI N

CO

2 H C1 N 4-Bromo-5-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2 carboxylic acid 'H-NMR(DMSO-dr, TMS)5(ppm):7.20(1H,s),7.67(1H,dd,J=8Hz,5Hz), 5 8.25 (1H, dd, J=8Hz, 2Hz), 8. 58 (1H, dd, J=5Hz, 2Hz) ,12. 99 (1H, brs) Reference Preparation Example 143-(3) According to the same manner as that of Reference Preparation Example 71-(5), 4-bromo-5-chloro-1-(3-chloro 2-pyridinyl)-1H-pyrrole-2-carboxylic acid and 2-amino-3, 5 10 dibromobenzoic acid were used in place of 4-bromo-1- (3-chloro 2-pyridinyl)-1H-pyrrole-2-carboxylic acid and 2-amino-5 chloro-3-methylbenzoic acid respectively to obtain 2-(4-bromo-5-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrrol-2-yl J-6,8-dibromo-4H-3,1-benzoxaziine-4-one of the formula: Br O0 CI N / N C1 NZ Br 15 Br 2-[4-Bromo-5-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrrol 2-yl]-6,8-dibromo-4H-3,1-benzoxazine-4-one 1 H-NMR(CDC1 3 ,TMS)b(ppm):7.49(1H,S),7.71(1H,dd,J=8Hz,5Hz), 8.11(1H,d,J=2Hz),8.26(1H,d,J=2Hz),8.34(1H,dd,J=8Hz,1Hz), ,7 08 8.63(1H,dd,J=5Hz,1Hz) Reference Preparation Example 143-(4) According to the same manner as that of Reference Preparation Example 71-(6), 2-[4-bromo-5-chloro-1-(3-chloro 5 2-pyridinyl)-lH-pyrrol-2-yl]-6,8-dibromo-4H-3,1-benzoxazine -4-one was used in place of 2-[4-bromo-l-(3-chloro-2 pyridinyl)-1H-pyrrol-2-yl]-6-chloro-8-methyl-4H- 3

,

1 benzoxazine-4-one to obtain 4-bromo-N-(4,6-dibromo-2 (hydrazinocarbonyl)phenyl)-5-chloro-1-(3-chloro-2-pyridinyl 10 )-1H-pyrrole-2-carboxamide of the formula: Br Br 0 BBr CB NI C1 N H NH2 N H 4-Bromo-N-[4,6-dibromo-2-(hydrazinocarbonyl)phenyl]-5 chloro-1-(3-chloro-2-pyridinyl)-1H-pyrrole-2-carboxamide

'H-NMR(CDC

3 , TMS)6(ppm):7.21(1H,s),7.39(1H,dd,J=8Hz,5Hz), 15 7.42(1H,d,J=2Hz),7.70(lH,d,J=2Hz),7.88(1H,dd,J=8Hz,2Hz), 8.49(lH,dd,J=5Hz,2Hz),8.71(lH,s) Reference Preparation Example 144 Under ice-cooling, 8.42 g of 2-[3-bromo-1-(3-chloro-2 pyridinyl)-1H-pyrazol-5-yl]-6,8-dibromo-4H-3,1-benzoxazine 20 4-one, 3.0 g of hydrazine monohydrate and 60 ml of tetrahydrofuran were mixed, and the mixture was stirred at room '709 temperature for 3 hours. A deposited precipitate was collected by filtration, and washed successively with tetrahydrofuran and methyl t-butyl ether to obtain 4.85 g of 3-bromo-N-[4,6 dibromo-2-(hydrazinocarbonyl)phenyl]-1-(3-chloro-2 5 pyridinyl)-1H- pyrazole-5-carboxamide of the formula: Br O Br Br N N C N H NNH2 Ci O N H 3-Bromo-N-(4,6-dibromo-2-(hydrazinocarbonyl)phenyl]-1 (3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide 1 H-NMR(DMSO-d 6 ,TMS)5(ppm):4.35(2H,brs),7.42(1H,s),7.58- 7

.

62 10 (2H,m),8.07(lH,d,J=2Hz),8.16(lH,dd,J=8Hz,2Hz),8.50(lH,dd, J=5Hz,2Hz),9.61(1H,brs) Reference Preparation Example 145 A mixture of 0.50 g of 6,8-dibromo-2-(4-bromo-1-(3 chloro-2-pyridinyl) -lH-pyrrol-2-yl] -4H-3, 1-benzoxazine-4 15 one, 0.15 ml of methylhydrazine and 8 ml of tetrahydrofuran was stirred at room temperature for 20 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and an aqueous saturated sodium chloride solution, dried over 20 anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel .710 chromatography to obtain 0.39 g of 4-bromo-N-[4,6-dibromo-2 (N-methylhydrazinocarbonyl) phenyl) -1- (3-chloro-2-pyridinyl) -1H-pyrrole-2-carboxamide of the formula: Br Br Br \AN N H

.NH

2 CI O N

H

3 C 5 4-Bromo-N-[4,6-dibromo-2-(N-methylhydrazinocarbonyl) phenyl) -1- (3-chloro-2-pyridinyl) -1H-pyrrole-2-carboxamide 'H-NMR (CDCl 3 , TMS)(ppm):2.96(1.5H,s), 3.15(1.5H, s), 4 .05(1.OH, s),4.48 (1.OH, s),7.03 (1.OH,d,J=2Hz),7.18 (0.5H,d, J=2Hz), 7.21(0.5H,d,J=2Hz),7.29-7.34(2.OH,m),7.63(0.5H,d,J=2Hz), 10 7.68(0.5H,d,J=2Hz),7.79-7.83(1.OH,m),8.40-8.44(1.0H,m), 8.67(0.5H,s),8.77(0.5H,s) Reference Preparation Example 146 A mixture of 1.0 g of 2-(3-bromo-1-(3-chloro-2 pyridinyl)-1H-pyrazol-5-yl]-6,8-dibromo-4H-3,1-benzoxazine 15 4-one, 0.28 ml of methylhydrazine and 16 ml of tetrahydrofuran was stirred at room temperature for 19 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and an aqueous saturated sodium chloride solution, dried 20 over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 0.97 g of 3-bromo-N-[4, 6- -711 dibromo-2- (N-methylhydrazinocarbonyl) phenyl] -1- (3-chloro-2 pyridinyl)-1H-pyrazole-5-carboxamide of the formula: Br Br Br N N N H

.NH

2 C1 O N N ' |N

H

3 C 3-Bromo-N-[4,6-dibromo-2-(N-methylhydrazinocarbonyl) 5 phenyl] -1- (3-chloro-2-pyridinyl) -1H-pyrazole-5-carboxamide 'H-NMR (CDCl 3 , TMS) 6 (ppm) :2. 97 (1. 5H, s) ,3.17 (1. 5H, s), 3

.

99 (1. OH, s),4.51(1.OH,s),7.31(1.OH,d,J=2Hz),7.35-7.41(2.0H,m), 7.61(0.5H,d,J=2Hz),7.67(0.5H,d,J=2Hz),7.84-7.89(1.OH,m), 8.45-8.50(1.OH,m),9.32(0.5H,s.),9.45(0.5H,s) 10 Reference Preparation Example 147 To a mixture of 0.42 g of N,N'-dimethylhydrazine dihydrochloride, five drops of water, 0.87 g of potassium carbonate and 10 ml of tetrahydrofuran was added 0.60 g of 2- [3-bromo-1- (3-chloro-2-pyridinyl) -1H-pyrazol-5-yl) -6,8 15 dibromo-4H-3,1-benzoxazine-4-one. The resulting mixture was stirred at room temperature for 19 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and an aqueous saturated sodium chloride solution, dried over 20 anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 0.51 g of 3-bromo-N-[4,6-dibromo-2- 712 ' (N,N'-dimethylhydrazinocarbonyl)phenyl]-1-(3-chloro-2 pyridinyl)-lH-pyrazole-5-carboxamide of the formula: Br Br Br 0~ N, N CH 3 N H H CI O N

H

3 C 3-Bromo-N-[4,6-dibromo-2-(N,N'-dimethylhydrazinocarbonyl) 5 phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide 1 H-NMR(CDCl 3 ,TMS)5(ppm):2.49(1.5H,d,J=6Hz),2.58 (1.5H,d, J=6Hz),2.92(1.5H,s),3.11(1.5H,s),3.52(0.5H,q,J=6Hz), 5.43(0.5H,q,J=6Hz),7.21(0.5H,s),7.24(0.5H,s),7.30(0.5H,d, J=2Hz),7.32(0.5H,d,J=2Hz),7.35-7.39(1.OH,m),7.61(0.5H,d, 10 J=2Hz),7.67(0.5H,d,J=2Hz),7.83-7.87(1.0H,m),8.44-8.4 7 (1.OH,m),9.24(0.5H,s),9.42(0.5H,s) Reference Preparation Example 148 To a mixture of 0.42 g of N,N'-dimethylhydrazine dihydrochloride, five drops of water, 0.87 g of potassium 15 carbonate and 10 ml of tetrahydrofuran was added 0.59 g of 6,8-dibromo-2-4-bromo--(3-chloro-2-pyridinyl)-1H-pyrrol 2-yl]-4H-3,1-benzoxazine-4-one. The resulting mixture was stirred at room temperature for 2 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl 20 acetate. The organic layer was washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced '713 pressure. The resulting residue was subjected to silica gel chromatography to obtain 0.52 g of 4-bromo-N-[4,6-dibromo-2 (N,N'-dimethylhydrazinocarbonyl)phenyl]-1-(3-chloro-2 pyridinyl)-lH-pyrrole-2-carboxamide of the formula: Br Br Br BN

CH

3 N H CI O N N '

H

3 C 5 4-Bromo-N-[4,6-dibromo-2-(N,N'-dimethylhydrazinocarbonyl) phenyl]-1-(3-chloro-2-pyridinyl)-lH-pyrrole-2-carboxamide 1 H-NMR(CDC1 3 ) 5:2. 47 (1.5H,d,J=6Hz) ,2. 55 (1.5H,brs) ,2. 91 (1.5H,s),3.08(1.5H,s),3.54(0.-5H,q,J=6Hz),5.46(0.5H,brs), 10 7.03(1.OH,d,J=2Hz),7.10(0.5H,d,J=2Hz),7.15(0.5H,d,J=2Hz), 7.28-7.32(2.OH,m),7.65(0.5H,d,J=2Hz),7.69(0.5H,d,J=2Hz), 7.77-7.81(1.OH,m),8.39-8. 41(1.5H,m),8.62 (0.5H, s). Reference Preparation Example 149-(1) To 10 ml of methanol were added 1.0 g of 3-chloro-2 15 (2-formyl-lH-pyrrol-1-yl)pyridine and 1.4 g of sodium thiocyanate. A solution of 1.0 g of bromine in 5 ml of saturated sodium bromide-methanol was added dropwise thereto at -20 0 C. The resulting mixture was stirred at the same temperature for 2 hours. The reaction mixture was added to 100 ml of ice water, 20 and extracted with chloroform two times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and -714 concentrated under reduced pressure to obtain 1.6 g of 1-(3-chloro-2-pyridinyl)-5-thiocyanato-lH-pyrrole-2 carbaldehyde of the formula: NC''Sk 4 T CHO CI N 5 1-(3-Chloro-2-pyridinyl)-5-thiocyanato-1H-pyrrole-2 carbaldehyde I H-NMR(CDC1,TMS)6(ppm):6.95(H,d,J=4Hz),7.16(1H,d,J=4Hz), 7.52(1H,dd,J=8Hz,5Hz),7.97(1H,dd,J=8Hz,2Hz),8.57(lH,dd, J=5Hz,2Hz),9.58(1H,s) 10 Reference Preparation Example 149-(2) According to the same manner as that of Reference Preparation Example 71-(4), 1-(3-chloro-2-pyridinyl)-5 thiocyanato-lH-pyrrole-2-carbaldehyde was used in place of 4-bromo-1-(3-chloro- 2-pyridinyl)-1H-pyrrole-2-carbaldehyde 15 to obtain 1- (3-chloro-2-pyridinyl) -5-thiocyanato-1H-pyrrole 2-carboxylic acid of the formula: NCS N CO 2 H Cl' N 1-(3-Chloro-2-pyridinyl)-5-thiocyanato-1H-pyrrole-2 carboxylic acid 715 1 H-NMR(DMSO-d 6 ,TMS)6(ppm):7.07(1H,d,J=4Hz),7.11(1H,d,J= 4 Hz), 7.69(1H,dd,J=8Hz,5Hz),8.27(1H,d,J=8Hz),8.62(1H,d,J=5Hz) Reference Preparation Example 149-(3) According to the same manner as that of Reference 5 Preparation Example 71-(5), 1-(3-chloro-2-pyridinyl)-5 thiocyanato-1H-pyrrole-2- carboxylic acid and 2-amino-3,5 dibromobenzoic acid were used in place of 4-bromo-1-(3-chloro 2-pyridinyl)-1H-pyrrole-2-carboxylic acid and 2-amino-5 chloro-3-methylbenzoic acid respectively to obtain 10 6, 8-dibromo-2- [1- (3-chloro-2-pyridinyl) -5-thiocyanato-lH pyrrol-2-yl)-4H- 3,1-benzoxazine-4-one of the formula: NCs 00 C, N "N Br Br 6, 8-Dibromo-2- [1- (3-chloro-2-pyridinyl) -5-thiocyanato-lH pyrrol-2-yl]-4H-3,1-benzoxazine-4-one 15 1H-NMR(DMSO-d 6 ,TMS)6(ppm):7.23(lH,d,J=4Hz),7.41(1H,d,J=4Hz), 7.72 (1H,dd, J=8Hz, 5Hz) ,8.14 (1H,d, J=2Hz) ,8.29 (1H, d,J=2Hz), 7.34(1H,d,J=8Hz),8.66(1H,d,J=5Hz) Reference Preparation Example 150 Under ice-cooling, 0.569 g of 6,8-dibromo-2-[4-bromo-1 20 (3-chloro-2-pyridinyl)-1H-pyrrol-2-yl]-4H-3,1-benzoxazine 4-one, 0.20 g of hydrazine monohydrate and 2 ml of tetrahydrofuran were mixed, and the mixture was stirred at room .716 temperature for 1 hour. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate, and concentrated under reduced pressure to obtain 0.53 g of' 5 4-bromo-N-[4,6-dibromo-2-(hydrazinocarbonyl)phenyl)-l-( 3 chloro-2-pyridinyl) -1H-pyrrole-2-carboxamide of the formula: Br Br Br B N rN H -NH2 Cl O N N H Reference Preparation Example. 151-(1) 10 A mixture of 1.0 g of 4-bromoimidazole, 1.3 g of 3-chloro-2-(methanesulfonyl)pyridine, 2.7 g of cesium carbonate and 10 ml of N,N-dimethylformamide was stirred at 100"C for 6 hours. The reaction mixture was allowed to cool to room temperature, and water was poured into the mixture. A 15 deposited precipitate was collected by filtration to obtain 1. 7 g of 2-(4-bromo-lH-imidazol-1-yl)-3-chloropyridine of the formula: Br N - N 2-(4-Bromo-1H-imidazol-1-yl)-3-chloropyridine .717 % 'H-NMR(CDCl 3 ,TMS)5(ppm):7.33(1H,dd,J=8HZ,5Hz),7.

63 (lH,S), 7.93(lH,dd,J=BHz,2Hz),8.13(lH,s),8.45-8.46(lH,m) Reference Preparation Example 151-(2) To a solution of 1.0 g of 2-(4-bromo-1H-imidazol-1-yl)-' 5 3-chloropyridine in 5 ml of dichloromethane was added dropwise a solution of 0.45 ml of trichloroacetyl chloride in 5 ml of dichloromethane at room temperature. The resulting mixture was stirred at room temperature for 1 day. Thereto 0.57 ml of triethylamine was added, and the resulting mixture was stirred 10 at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was subjected to silica gel chromatography to obtain 1.0 g of 1-[4-bromo-1-(3-chloro-2-pyridinyl)-1H-imidazol-2-yl] 2,2,2-trichloroethanone of the formula: Br N C1 CIC 15 1- [4-Bromo-1- (3-chloro-2-pyridinyl) -1H-imidazol-2-yl] 2,2,2-trichloroethanone 1 H-NMR(CDCl 3 ,TMS)5(ppm):7.35(1H,s),7.49(1H,dd,J=8Hz,5Hz), 7.95(1H,dd,J=8Hz,2Hz),8.51(1H,dd,J=5Hz,2Hz) 20 Reference Preparation Example 151-(3) To a solution of 0.50 g of 1-[4-bromo-1-(3-chloro-2 pyridinyl)-lH-imidazol-2-yl]-2,2,2-trichloroethanone and .718 0.37 g of 2-amino-3,5-dibromobenzoic acid in 10 ml of acetonitrile was added 0.43 ml of triethylamine. The resulting mixture was stirred at room temperature for 1 day. Thereto 0.12 ml of methanesulfonyl chloride was added, and the mixture was' 5 stirred at room temperature for 3 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced 10 pressure. The residue was subjected to silica gel column chromatography to obtain 0.29 g of 2-[4-bromo-1-(3-chloro-2 pyridinyl)-lH-imidazol-2-yl]-6,8-dibromo-4H-3,1-benzoxazine -4-one of the formula: Br CI N Br Br 15 2-[4-Bromo-l-(3-chloro-2-pyridinyl)-lH-imidazol-2-yl]-6, 8 dibromo-4H-3,1-benzoxazine-4-one. 'H-NMR(DMSO-dsTMS)6(ppm):7.70(lH,dd,J=8Hz,5Hz),8.18(lH,d, J=3Hz),8.18(lH,s),8.31(lH,dd,J=8Hz,1Hz),8.33(1H,d,J=3Hz), 8.59 (1H,dd, J=5Hz, 1Hz) 20 Reference Preparation Example 152-(1) A mixture of 0.70 g of 1-(3-chloro-2-pyridinyl)-5 thiocyanato-lH-pyrrole-2-carbaldehyde, 0.64 g of sodium ,719 sulfide nonahydrate and 10 ml of water was stirred for 1 hour under heat refluxing. The reaction mixture was allowed to cool to room temperature, adjusted to pH 5 by an addition of acetic acid, and then extracted with ethyl acetate two times. The' 5 organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was washed with methyl tert-butyl ether to obtain 0.50 g of 1-(3-chloro-2-pyridinyl)-5-mercapto-1H-pyrrole-2 10 carbaldehyde of the formula: HS N CHO CI NN 1-(3-Chloro-2-pyridinyl)-5-mercapto-lH-pyrrole-2 carbaldehyde IH-NMR(CDCl 3 ,TMS)5(ppm):6.56(lH,d,J=4Hz),7.07(lH,d,J=4Hz), 15 7.46(lH,dd,J=BHz,5Hz),7.93(lH,dd,J=8Hz,2Hz),8.54(lH,dd, J=5Hz,2Hz),9.42(1H,s) Reference Preparation Example 152-(2) A mixture of 0.50 g of 1-(3-chloro-2-pyridinyl)-5 mercapto-lH-pyrrole-2- carbaldehyde, 0.36 g of methyl iodide, 20 0.43 g of potassium carbonate and 50 ml of N,N-dimethylformamide was stirred at room temperature for 1 day. Water was poured into the reaction mixture, and the mixture was 720 extracted with ethyl acetate three times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure.' 5 The residue was subjected to silica gel column chromatography to obtain 0.34 g of 1-(3-chloro-2-pyridinyl)-5-methylthio-lH pyrrole-2-carbaldehyde of the formula:

H

3 CS N CHO CI N 1-(3-Chloro-2-pyridinyl)-5-methylthio-1H-pyrrole-2 10 carbaldehyde 1 H-NMR(CDCl 3 ,TMS)5(ppm):2.39(3H,s),6.45(lH,d,J=4Hz), 7.10(lH,d,J=4Hz),7.43(lH,dd,J=8Hz,5Hz),7.90(lH,dd,J=8Hz, 2Hz),8.52(lH,dd,J=5Hz,2Hz),9.41(lH,s) Reference Preparation Example 152-(3) 15 To a mixture of 0.38 g of 1-(3-chloro-2-pyridinyl)-5 methylthio-1H-pyrrole-2-carbaldehyde, 5 ml of acetone and 3 ml of water was added 0.38 g of potassium permanganate at 40 0 C. The resulting mixture was stirred at 50 0 C for 4 hours. The reaction mixture was allowed to cool to room temperature, and 20 filtered. The filtrate was washed with chloroform two times, and then adjusted to around pH 3 by an addition of 2N hydrochloric acid. A deposited crystal was collected by ,721 filtration to obtain 0.38 g of a mixture of 1-(3-chloro-2 pyridinyl) -5-methylsulfonyl-lH-pyrrole- 2 -carboxylic acid and 1-(3-chloro-2-pyridinyl)-5-methylthio-lH-pyrrole-2 carboxylic acid. 5 A mixture of the resulting mixture and 0.29 ml of thionyl chloride was heated to reflux in 10 ml of acetonitrile for 1 hour. The reaction mixture was allowed to cool to room temperature, and concentrated under reduced pressure. The resulting residue was dissolved in 10 ml of acetonitrile. 10 Thereto 0.39 g of 2-amino-3,5-dibromobenzoic acid and 0.65 ml of triethylamine were added, and the mixture was stirred at room temperature for 6 hours. Thereto 0.13 ml of methanesulfonyl chloride was added, and the mixture was stirred at room temperature for 1 hour. Water was poured into the reaction 15 mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography 20 to obtain 0.05 g of 6,8-dibromo-2-[1-(3-chloro-2-pyridinyl) 5-methylsulfonyl-1H-pyrrol- 2 -yl)-4H-3,1-benzoxazine-4-one of the formula: 722 0

H

3 CS O 0 C0 N/ N 5.Br Br and 0.05 g of 6, 8-dibromo-2-[1-(3-chloro-2-pyridinyl)-5 methylthio-1H-pyrrol-2-yl)-4H-3,1-benzoxazine-4-one of the formula:

H

3 C-S O O N N &Br 5 Br . 6,8-Dibromo-2-[l-(3-chloro-2-pyridinyl)-5-methylsulfonyl 1H-pyrrol-2-yl)-4H-3,1-benzoxazine-4-one 1H-NMR(CDCl 3 ,TMS)6(ppm):3.23(3H,s),7.21(1H,d,J=4Hz), 7

.

4 1(1H, d,J=4Hz),7.50(1H,dd,J=8Hz,4Hz),7.95(1H,d,J=8Hz),8.02(1H,d, 10 J=2Hz),8.24(lH,d,J=2Hz),8.56(lH,d,J=4Hz) 6,8-Dibromo-2-[1-(3-chloro-2-pyridinyl)-5-methylthio-1H pyrrol-2-yl]-4H-3,1-benzoxazine-4-one 'H-NMR(CDCl3,TMS)5(ppm):2.39(3H,s),6.63(1H,d,J=4Hz), 7

.

3 5(1H, 15 d,J=4Hz),7.63(1H,dd,J=8Hz,5Hz),8.08(1H,d,J=2Hz),8.22(1H,d, J=2Hz),8.25(1H,dd,J=BHz,2Hz),8.58(lH,dd,J=5Hz,2Hz) Reference Preparation Example 153-(1) To a mixture of 20 g of 3-chloro-2-hydrazinopyridine, 56 ml of sodium ethoxide (a 21% solution in ethanol) and 75 ml of ,723 ethanol was added dropwise 27 ml of diethyl maleate. The resulting mixture was heated to reflux for 10 minutes. The reaction mixture was allowed to cool to 65*C, and 15 ml of acetic acid was poured into the mixture. The reaction mixture was' 5 allowed to cool to room temperature. After 190 ml of water was poured into the reaction mixture, the mixture was adjusted to pH 2 by an addition of 6N hydrochloric acid and then extracted with methyl tert-butyl ether three times. The organic layers were combined, washed with an aqueous saturated sodium chloride 10 solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Diethyl ether was added to the resulting residue, and, a solid was collected by filtration to obtain 4.28 g of ethyl 2-(3-chloro-2-pridinyl) 5-oxo-3-pyrazolidinecarboxylate of the formula: 0 O HN% OCH 2

CH

3 N CI N 15 Ethyl 2-(3-chloro-2-pyridinyl)-5-oxo-3 pyrazolidinecarboxylate H-NMR(DMSO-d 6 , TMS)5(ppm) :1.22(3H, t, J=7Hz), 2.36 (lH, d, J=17Hz),2.92(lH,dd,J=17Hz,10Hz),4.20(2H,q,J=7Hz),4.83(lH,d, 20 J=lOHz),7.20(1H,dd,J=8Hz,5Hz),7.93(lH,d,J=8Hz),8.

27 (lH,d,J= 5Hz) ,10.17 (lH, s) Reference Preparation Example 153-(2) 724 To a mixture of 12.0 g of ethyl 2-(3-chloro-2-pyridinyl) 5-oxo-3-pyrazolidinecarboxylate, 90 ml of acetonitrile and 4.8 ml of sulfuric acid was added 14.5 g of potassium persulfate. The resulting mixture was heated to reflux for 3.5 hours. The' 5 reaction mixture was allowed to cool to room temperature, and filtered. Water was poured into the filtrate, and the mixture was extracted with methyl tert-butyl ether three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium 10 sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 7.23 g of ethyl 1-(3-chloro-2-pyridinyl)-3-hydroxy lH-pyrazole-5-carboxylate of the formula: HO C N

OCH

2

CH

3 N

CI

15 Ethyl 1-(3-chloro-2-pyridinyl)-3-hydroxy-1H-pyrazole-5 carboxylate 'H-NMR(DMSO-d 6 ,TMS)5 (ppm) :1. 06 (3H,t,J=7Hz) ,4. 11 (2H,q, J=7Hz), 6.34(1H,s),7.59-7.63(1H,m),8.17-8.23(1H,m),8.50-8.52(1H,m), 10.65(1H,s) 20 Reference Preparation Example 153-(3) Trifluoromethyl trifluorovinyl ether was blown into a mixture of 1.0 g of ethyl 1-(3-chloro-2-pyridinyl)-3-hydroxy- -725 1H-pyrazole-5-carboxylate, 0.042 g of potassium hydroxide, 10 ml of methanol and 10 ml of dimethyl sulfoxide under ice-cooling. The resulting mixture was stirred at room temperature for 4 days. Water was poured into the reaction mixture, and the mixture was' 5 extracted with diethyl ether two times. The organic layers were combined, washed with water and an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 1.32 g of 10 methyl 1-(3-chloro-2-pyridinyl)-3-[1,1,2-trifluoro- 2 (trifluoromethoxy) ethoxy) -lH-pyrazole-5-carboxylate of the formula:

F

3 CO H 00 F N

OCH

3 N CI NN Methyl 1-(3-chloro-2-pyridinyl)-3-[1,1,2-trifluoro-2 15 (trifluoromethoxy)ethoxy]-1H-pyrazole-5-carboxylate 'H-NMR(CDC1 3 ,TMS)5(ppm):3.80(3H,s),6.04(lH,dt,J=54Hz,3Hz), 6.80(lH,s),7.45(lH,dd,J=8Hz,5Hz),7.92(lH,dd,J=8Hz,2Hz),8.51 (1H, dd, J=5Hz,2H z) Reference Preparation Example 153-(4) 20 To a mixture of 1. 32 g of methyl 1- (3-chloro-2-pyridinyl) 3- [1,1, 2-trifluoro-2- (trifluoromethoxy) ethoxy] -1H-pyrazole- 726 1 5-carboxylate and 15 ml of methanol was added 5 ml of a 2N aqueous sodium hydroxide solution. The resulting mixture was stirred at room temperature for 3 hours. Water was poured into the reaction mixture, and the mixture was washed with methyl' 5 tert-butyl ether. The 'aqueous layer was adjusted to pH 2 by an addition of 6N hydrochloric acid and then extracted with methyl tert-butyl ether two times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and 10 concentrated under reduced pressure to obtain 1.18 g of 1- (3-chloro-2-pyridinyl) -3- [1,1, 2-trifluoro-2 (trifluoromethoxy)ethoxy]-1H-pyrazole-5-carboxylic acid of the formula:

F

3 C HF 0 0 F F\ FF N OH N CI N 15 1-(3-Chloro-2-pyridinyl)-3-[1,1,2-trifluoro-2 (trifluoromethoxy)ethoxy]-lH-pyrazole-5-carboxylic acid H-NMR(CDC1 3 ,TMS)6(ppm):6.04(lH,dt,J=54Hz,3Hz),6.84(lH,s), 7.46(lH,dd,J=8Hz,5Hz),7.93(lH,dd,J=8Hz,2Hz),8.50(lH,dd,J= 5Hz,2Hz) 20 Reference Preparation Example 153-(5) According to the same manner as that of Reference .727 Preparation Example 13, 1-(3-chloro-2-pyridinyl) -3-[1,1,2 trifluoro-2-(trifluoromethoxy)ethoxy]-1H-pyrazole-5 carboxylic acid was used in place of 1-(3-chloro-2 pyridinyl)-lH-pyrazole-5-carboxylic acid to obtain 6-chloro 5 2-{1-(3-chloro-2-pyridinyl)-3-[1,1,2-trifluoro- 2 (trifluoromethoxy)ethoxy]-1H-pyrazol-5-yl)-8-methyl-4H- 3 ,1 benzoxazine-4-one of the formula:

F

3 C HF FF N, 0 0 'N _N)

H

3 C CI 6-Chloro- 2-{1-(3-chloro-2-pyridinyl)-3-[1,1,2-trifluoro- 2 10 (trifluoromethoxy)ethoxy]-lH-pyrazol-5-yl)- 8 -methyl- 4

H-

3 ,1 benzoxazin-4-one 1H-NMR(CDCl 3 ,TMS) 5 (ppm) :1.83 (3H, s) ,6.06(1H,dt,J=5 4 Hz, 3 Hz) , 7 .04(lH,s),7.48-7.51(2H,m),7.'96-8.00(2H,m),8.55(lH,dd,J=5Hz, 2Hz) 15 Reference Preparation Example 154-(1) To a mixture of 4.0 g of N,N-dimethyl-lH-pyrazole-1 sulfonamide and 50 ml of tetrahydrofuran was added dropwise 15.7 ml of a 1.6M solution of N-butyl lithium in hexane at -78*C. The resulting mixture was stirred at -78"C for 10 minutes. A 20 mixture of 1.46 g of sulfur and 20 ml of tetrahydrofuran was added to the mixture. The mixture was stirred at -78*C for 1 728 hour, and further stirred for 1.5 hours while the reaction temperature was gradually raised to room temperature. A deposited solid was collected by filtration, and washed with diethyl ether. The solid was dissolved in water. The resulting' 5 aqueous solution was adjusted to around pH 3 by an addition of 6N hydrochloric acid, and then extracted with methyl t-butyl ether three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to 10 obtain 3.92 g of N,N-dimethyl-5-mercapto-lH-pyrazole-l sulfonamide of the formula: N SH S0 2

N(CH

3

)

2 N,N-Dimethyl-5-mercapto-1H-pyrazole-l-sulfonamide 'H-NMR (CDCl 3 , TMS) 6 (ppm) :3.03 (6H, s) ,4.39 (1H, s) ,6.

27 (1H, d, J= 15 2Hz),7.59(1H,d,J=2Hz) Reference Preparation Example 154-(2) A mixture of 1.0 g of N,N-dimethyl-5-mercapto-lH pyrazole-1-sulfonamide, 0.30 g of sodium hydride (50% in oil) and 25 ml of tetrahydrofuran was stirred at room temperature 20 for 0.5 hour, and then cooled to -60"C. Thereto 1.94 g of S-(trifluoromethyl)dibenzothiophenium trifluoromethanesulphonate was added. The resulting mixture was stirred at -60*C for 0.5 hour, and further stirred at room ,729 temperature for 2 hours. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate three times. The organic layers were combined, washed with an aqueous saturated sodium chloride solution, dried over magnesium 5 sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography to obtain 1.30 g of N,N-dimethyl-5-(triflioromethylthio)-1H pyrazole-l-sulfonamide of the formula: NN CF 3

SO

2

N(CH

3

)

2 10 N,N-Dimethyl-5-(triflioromethylthio)-lH-pyrazole-l sulfonamide 'IH-NMR(CDCl,TMS)5(ppm):3.08(6H,s),6.73(1H,s),7.73(lH,s) Reference Preparation Example 154-(3) According to the same manner as that of Reference 15 Preparation Example 21, N,N-dimethyl-5 (trifluoromethylthio)-lH-pyrazole-1-sulfoneamide was used in place of 5-bromo-N,N-dimethyl-lH-pyrazole-l-sulfonamide to obtain 3-(trifluoromethylthio)-lH-pyrazole of the formula:

F

3 C-S N5 N H. 20 3-(Trifluoromethylthio)-1H-pyrazole 'H-NMR(CDCl 3 ,TMS) 6(ppm) :6.70 (1H,d,J=3Hz) ,7.74 (1H,d,J=3Hz) , .730 12.47 (1H,brs) Reference Preparation Example 154-(4) According to the same manner as that of Reference Preparation Example 22, 3-(trifluoromethylthio)-lH-pyrazole' 5 was used in place of 3-bromo-lH-pyrazole to obtain 3-chloro-2 [3-(trifluoromethylthio)-lH-pyrazol-1-yl]pyridine of the formula:

F

3 C-S N C1 3-Chloro-2-[3-(trifluoromethylthio)-1H-pyrazol 10 1-yllpyridine 'H-NMR(CDCl 3 ,TMS)5(ppm) :6.78 (1H,d,J=3Hz),7.35(1H,dd,J=8Hz, 5Hz),7.94(1H,dd,J=8Hz,2Hz),8.17(1H,d,J=3Hz),8.47(1H,dd,J= 5Hz,2Hz) Reference Preparation Example 154-(5) 15 According to the same manner as that of Reference Preparation Example 23, 3-chloro-2-[3-(trifluoromethylthio) lH-pyrazol-1-yllpyridine was used in place of 2-(3-bromo-1H pyrazol-1-yl)-3-chloropyridine to obtain 1-(3-chloro-2 pyridinyl)-3-(trifluoromethylthio)-1H-pyrazole-5-carboxylic 20 acid of the formula: 731

F

3 C-S 'N COOH C1N 1-(3-Chloro-2-pyridinyl)-3-(trifluoromethylthio)-lH pyrazole-5-carboxylic acid 1H-NMRM(CDCl 3 ,TMS)6(ppm):7.35(1H,s),7.47(1H,dd,J= 8 Hz,5Hz), 5 7.94(lH,d,J=8Hz),8.52(lH,d,J=5Hz) Reference Preparation Example 154-(6) According to the same manner as that of Reference Preparation Example 13, 1-(3-chloro-2-pyridinyl)-3 (trifluoromethylthio) -1H-pyrazole-5-carboxylic acid was used 10 in place of 1-(3-chloro-2-pyridinyl)-1H-pyrazole-5 carboxylic acid to obtain 6-chloro-2-[1-(3-chloro-2 pyridinyl)-3-(trifluoromethylthio)-lH-pyrazol-5-yl)-8 methyl-4H-3,1-benzoxazine-4-one of the formula:

F

3 C-S Cl N - N 1

H

3 C C. 15 6-Chloro-2-[1-(3-chloro-2-pyridinyl)-3 (trifluoromethylthio)-1H-pyrazol-5-yl)-8-methyl-4H-3,1 benzoxazin-4-one lH-NMR (CDC13,TMS) 6(ppm) :1. 82 (3H, s) ,7. 50-7. 54 (3H,m), 732 7.98-8.00(2H,m),8.57(lH,dd,J=5Hz,2HZ) Reference Preparation Example 155 According to the same manner as that of Reference Preparation Example 147, 2-[3-bromo-1-(3-chloro-2 5 pyridinyl)-lH-pyrazol-5-yl)-6,8-dichloro-4H-3,1-benzoxazin 4-one was used in place of 2-[3-bromo-l-(3-chloro-2 pyridinyl)-1H-pyrazol-5-yl]-6,8-dibromo-4H-3,1-benzoxazin 4-one to obtain 3-bromo-N-[4,6-dichloro-2-(N,N' dimethylhydrazinocarbonyl)phenyl]-1-(3-chloro-2 10 pyridinyl)-lH-pyrazole-5-carboxamide of the formula: BrCI C1 N, N CH 3 N H NH C N 0 N

H

3 C 3-Bromo-N-[4,6-dichloro-2-(N,N' dimethylhydrazinocarbonyl) phenyl] -1- (3-chloro-2-pyridinyl) 1H-pyrazole-5-carboxamide 15 'H-NMR (DMSO-ds, TMS) 6 (ppm) :2. 20 (2. 4H, d, J=5H z) , 2. 39 (0.1 6 H, d, J= 6Hz),2.72(0.6H,s),3.02(2.4H,s),4.59(0.8H,q,J=5Hz),5.68(0.

2 H, q,J=6Hz),7.38(0.8H,d,J=2Hz),7.40(1.OH,s),7.53(0.2H,d,J=2Hz), 7.60-7.64(1.0H,m),7.70(0.8H,d,J=2Hz),7.84(0.2H,d,J=2Hz), 8.16-8.19(1.OH,m),8.49-8.50(1.OH,m),10.34(0.8H,s),10.

6 5 20 (0.2H,s) Then, Formulation Examples will be shown. All parts are 733 by weight. Formulation Example 1 Into a mixture of 35 parts of xylene and 35 parts of N,N-dimethylformamide, 10 parts of any one of the present 5 compounds (1) to (231) is dissolved, and then 14 parts of polyoxyethylene styrylphenyl ether and 6 parts of calcium dodecylbenzenesulfonate are added. The mixture is stirred thoroughly to obtain a 10% emulsion. Formulation Example 2 10 To a mixture of 4 parts of sodium laurylsulfate, 2 parts of calcium ligninsulfonate, 20 parts of synthetic hydrous silicon oxide fine powder and 54 parts of diatomaceous earth, 20 parts of any one of the present compounds (1) to (231) is added. The mixture is stirred thoroughly to obtain a 20% 15 wettable agent. Formulation Example 3 To 2 parts of any one of th'e present compounds (1) to (231) , 1 part of synthetic hydrous silicon oxide fine powder, 2 parts of calcium ligninsulfonate, 30 parts of bentonite and 65 parts 20 of kaolin clay are added, and then stirred thoroughly. Then, an appropriate amount of water is added to the mixture. The mixture is further stirred, granulated with a granulator, and forced-air dried to obtain a 2% granule. Formulation Example 4 25 Into an appropriate amount of acetone, 1 part of any one .734 of the present compounds (1) to (231) is dissolved, and then 5 parts of synthetic hydrous silicon oxide fine powder, 0.3 part of PAP and 93.7 parts of fubasami clay are added. The mixture is stirred thoroughly. Then, acetone is removed from the 5 mixture by evaporation to obtain a 1% powder. Formulation Example 5 A mixture of 10 parts of any one of the present compounds (1) to (231) ; 35 parts of white carbon containing 50 parts of polyoxyethylene alkyl ether sulfate ammonium salt; and 55 parts 10 of water is finely ground by a wet grinding method to obtain a 10% flowable agent. Formulation Example 6 In 5 parts of xylene and 5 parts of trichloroethane, 0.1 part of any one of the present compounds (1) to (231) is 15 dissolved. The solution is mixed with 89.9 parts of deodorized kerosene to obtain a 0.1% oil. Formulation Example 7 In 0.5 ml of acetone, 10 mg of any one of the present compounds (1) to (231) is dissolved. The solution is mixed 20 uniformly with 5 g of a solid feed powder for an animal (solid feed powder for rearing and breeding CE-2, manufactured by CLEA Japan, Inc.), and then dried by evaporation of acetone to obtain poison bait. Then, it will be shown by Test Examples that the present 25 compound is effective in controlling harmful arthropods.

-735 Test Example 1 Preparations of the present compounds (1), (4) to (53), (55) to (74), (76) to (83), (85) to (120), (122) to (156), (158) to (167), (170) to (171), (173), (175) to (176), (178), (181) 5 to (184), (188) to (190)', (195) to (197), (200) to (216), (218) to (219), (221) to (223) and (231) obtained in Formulation Example 5 were diluted with water so that the active ingredient concentration became 500 ppm, to prepare test spray solutions. -At the same time, cabbage was planted in a polyethylene 10 cup, and grown until the third true leaf or the fourth true leaf was developed. The test spray solution as described above was sprayed in an amount of 20 ml-/cup on the cabbage. After the drug solution sprayed on the cabbage was dried, 10 third-instar larvae of diamondback moths were put on the 15 cabbage. After 5 days, the number of diamondback moths was counted, and a controlling value was calculated by the following equation: Controlling value(%) = {1-(Cb x Tai)/(Cai x Tb)) x 100 wherein, 20 Cb: the number of worms in a non-treated section before treatment Cal: the number of worms in a non-treated section on observation Tb: the number of worms in a treated-section before 25 treatment .736 Tal: the number of worms in a treated-section on observation. As a result, the test spray solutions of the present compounds (1), (4) to (53), (55) to (74), (76) to (83), (85)' 5 to (120), (122) to (156), (158) to (167), (170) to (171), (173), (175) to (176), (178), (181) to (184), (188) to (190), (195) to (197), (200) to (216), (218) to (219), (221) to (223) and (231) each exhibited a controlling value of 80% or more. Test Example 2 10 Preparations of the present compounds (4) to (7), (9) to (12), (17) to (23), (27), (29), (32) to (44), (48) to (51), (56) to (61), (65) to (68), (70) to (72), (74) to (75), (78) to (81), (83) to (85), (87) to (88), (91) to (97), (99) to (102), (104) to (120), (122) to (125), (127) to (135), (137) to (144), (147) 15 to (149), (151) to (161), (164), (166) to (168), (171) to (173), (175) to (184), (186) to (188), (191), (193) to (205), (208) to (209), (213) to (215), (218) to (224), (226) to (230) and (231) obtained in Formulation Example 5 was diluted with water so that the active ingredient concentration became 500 ppm to 20 prepare test spray solutions. At the same time, cucumber was planted in a polyethylene cup, and was grown until the first true leaf was developed. About 30 cotton aphids were put on the cucumber. One day after, the test spray solution as described above was sprayed in an 25 amount of 20 ml/cup on the cucumber. Six days after spraying, ,737 the number of cotton aphids was counted, and a controlling value was calculated by the following equation: Controlling value(%) = {1-(Cb x Tai)/(Cai x Tb)) x 100 wherein, 5 Cb: the number of insects in a non-treated section before treatment Cai: the number of insects in a non-treated section on observation Tb: the number of insects in a treated-section before 10 treatment Tai: the number of insects in a treated-section on observation. As a result, the test spray solutions of the present compounds (4) to (7), (9) to (12), (17) to (23), (27), (29), 15 (32) to (44), (48) to (51), (56) to (61), (65) to (68), (70) to (72), (74) to (75), (78) to (81), (83) to (85), (87) to (88), (91) to (97), (99) to (102), (104) to (120), (122) to (125), (127) to (135), (137) to (144), (147) to (149), (151) to (161), (164), (166) to (168), (171) to (173), (175) to (184), (186) 20 to (188), (191), (193) to (205), (208) to (209), (213) to (215), (218) to (224), (226) to (230) and (231) each exhibited a controlling value of 90% or more. Furthermore, the same way as Test Example 2, test spray salution of the comparative compound of the formula: 738 H3C

F

3 C N C1N H O N'CH2 OCH3 N H (disclosed in W02003/015518A page 109 Compound 354) exhibited a controlling value of less than 30 %. Test Example 3 5 Preparations of the present compounds (4) to (13), (15) to (23), (25) to (44), (48) to (51), (56) to (58), (61), (65) to (74), (80) to (81), (85) to (97), (100), (102), (104) to (120), (122),to (125), (127) to (137), (139) to (156), (158) to (167), (170) to (171), (173), (175) to (176), (178), (181) to (184), 10 (188) to (190), (195) to (197), (200) to (208), (210) to (216), (218) to (219), (221) to (224) and (231) obtained in Formulation Example 5 was diluted with water so that the active ingredient concentration became 500 ppm to prepare test spray solutions. At the same time, cabbage was planted in a polyethylene 15 cup, and grown until the third true leaf or the fourth true leaf was developed. The test spray solution as described above was sprayed in an amount of 20 ml/cup on the cabbage. After the drug solution sprayed on the cabbage was dried, 10 fourth-instar larvae of Spodoptera litura were put on the 20 cabbage. After 4 days, the number of Spodoptera litura surviving on the cabbage leaves was counted, and a controlling value was calculated by the following equation: 739 Controlling value(%) = {1-(Cb x Tai)/(Cai x Tb)} x 100 wherein, Cb: the number of worms in a non-treated section before treatment 5 Cai: the number of worms in a non-treated section on observation Tb: the number of worms in a treated-section before treatment Tai: the number of worms in a treated-section on 10 observation. As a result, the test spray solutions of the present compounds (4) to (13), (15) to (23), (25) to (44), (48) to (51), (56) to (58), (61), (65) to (74), (80) to (81), (85) to (97), (100), (102), (104) to (120), (122) to (125), (127) to (137), 15 (139) to (156), (158) to (167), (170) to (171), (173), (175) to (176), (178), (181) to (184), (188) to (190), (195) to (197), (200) to (208), (210) to (216), (218) to (219), (221) to (224) and (231) each exhibited a controlling value of 80% or more. Test Example 4 20 Preparations of the present compounds ) (4) to (13), (15) to (23), (25) to (45), (47) to (51), (53), (55) to (61), (65) to (72), (74), (78) to (81), (83), (85) to (102), (104) to (105), (107) to (117), (119) to (120), (122) to (125), (127) to (156), (158) to (164), (166) to (167), (171), (173), (175) to (176), 25 (178), (181) to (184), (188) to (190), (195) to (197), (200) -740 to (211) , (213) to (216), (218) to (219), (221) to (224) and (231) obtained in Formulation Example 5 was diluted with water so that the active ingredient concentration became 500 ppm to prepare test spray solutions. 5 At the same time, '20 ml of the test spray solution as described above was sprayed to an apple seedling (28 day-old seeding, tree height: about 15 cm) planted in a plastic cup. The apple seedling was air-dried to such an extent that the drug solution sprayed on the apple seedling was dried, about 30 10 first-instar larvae of Adoxophyes orana fasciata were released. Seven days after spraying, the number of worms surviving on the apple seedling was counted, and a controlling value was calculated by the following equation: Controlling value(%) = {1-(Cb x Tai)/(Cai x Tb)) x 100 15 wherein, Cb: the number of worms in a non-treated section before treatment Cai: the number of worms in a non-treated section on observation 20 Tb: the number of worms in a treated-section before treatment Tai: the number of worms in a treated-section on observation. As a result, the test spray solutions of the present 25 compounds (4) to (13), (15) to (23), (25) to (45), (47) to (51), 741 (53), (55) to (61), (65) to (72), (74), (78) to (81), (83), (85) to (102), (104) to (105), (107) to (117), (119) to (120), (122) to (125), (127) to (156), (158) to (164), (166) to (167), (171), (173), (175) to (176), (178), (181) to (184), (188) to (190), 5 (195) to (197), (200) to (211), (213) to (216), (218) to (219), (221) to (224) and (231) each exhibited a controlling value of 90% or more. Test Example 5 Preparations of the present compounds (4) to (5), (9) to 10 (10), (17), (19) to (22), (27), (29), (32) to (44), (48) to (51), (56) to (61), (66) to (68), (70) to (72), (74) to (75), (79), (81), (85), (88), (91) to (92), (94) to (95), (99), (101) to (102), (104) to (120), (122) to (124), (127) to (129), (131) to (132), (135) to (136), (140), (142) to (145), (147) to (151), 15 (153) to (157), (159), (163) to (164), (167), (171) to (172), (175) to (176), (183), (187), (193) to (194), (196) to (204), (206), (208) to (209), (213) to (221), (226), (227) and (231) obtained in Formulation Example 5 was diluted with water so that the active ingredient concentration became 500 ppm to prepare 20 test spray solutions. At the same time, cucumber was planted in a polyethylene cup, and was grown until the first true leaf was developed. The test spray solution as described above was sprayed in an amount of 20 ml/cup on the cucumber. After the drug solution sprayed 25 on the cucumber was dried, the first true leaf was cut and then .742 placed on a filter paper (diameter: 70 mm) containing water in a polyethylene cup (diameter: 110 mm) . On the cucumber leaf, 20 larvae of Frankliniella occidentalis were released, and the polyethylene cup was capped. Seven days after spraying, the' 5 number of insects surviving on the cucumber leaf was counted, and a controlling value was calculated by the following equation: Controlling value(%) = {l-(Cb x Tai)/(Cai x Tb)) x 100 wherein, 10 Cb: the number of insects in a non-treated section before treatment Cai: the number of insects in a non-treated section on observation Tb: the number of insects in a treated-section before 15 treatment Tai: the number of insects in a treated-section on observation. As a result, the test spray solutions of the present 20 compounds (4) to (5), (9) to (10), (17), (19) to (22), (27), (29), (32) to (44), (48) to (51), (56) to (61), (66) to (68), (70) to (72), (74) to (75), (79), (81), (85), (88), (91) to (92), (94) to (95), (99), (101) to (102), (104) to (120), (122) to (124), (127) to (129), (131) to (132), (135) to (136), (140), 25 (142) to (145), (147) to (151), (153) to (157), (159), (163) 743 to (164), (167), (171) to (172), (175) to (176), (183), (187), (193) to (194), (196) to (204), (206), (208) to (209), (213) to (221), (226), (227) and (231) each exhibited a controlling value of 90% or more. 5 Test Example 6 Preparations of the present compounds (5), (32), (34), (43) to (44), (49) to (50), (56), (59), (93), (95) to (96), (107), (111) to (112), (114), (119), (127), (129), (132) to (133), (144), (147) to (148), (153), (158), (167) to (168), (171) to 10 (172), (177) to (178), (182) to (184), (186) to (187), (193) to (194), (197) to (199), (201), (204), (209), (213), (215), (219) to (220), (221), (223), (226) and (231) obtained in Formulation Example 5 was diluted with water so that the active ingredient concentration became 500 ppm to prepare test spray 15 solutions. At the same time, cabbage was planted in a polyethylene cup, and grown until the first true leaf was developed. All leaves excluding the first true leaf were cut off. On the first true leaf, imagoes of silver leaf whitefly were released and 20 allowed to lay eggs for about 24 hours. The cabbage was retained in a greenhouse for 8 days. When larvae hatched from the laid eggs, the test spray solution as described above was sprayed in an amount of 20 ml/cup to the cabbage. Seven days after spraying, the number of larvae surviving on the cabbage was 25 counted, and a controlling value was calculated by the 744 following equation: Controlling value(%) = {l-(Cb x Tai)/(Cai x Tb)) x 100 wherein, Cb: the number of worms in a non-treated section before 5 treatment Cai: the number of worms in a non-treated section on observation Tb: the number of worms in a treated-section before treatment 10 Tai: the number of worms in a treated-section on observation. As a result, the test spray solutions of the present compounds (5), (32), (34), (43) to (44), (49) to (50), (56), (59), (93), (95) to (96), (107), (111) to (112), (114), (119), 15 (127), (129), (132) to (133), (144), (147) to (148), (153), (158), (167) to (168), (171) to (172), (177) to (178), (182) to (184), (186) to (187), (193) to (194), (197) to (199), (201), (204), (209), (213), (215), (219) to (220), (221), (223), (226) and (231) each exhibited a controlling value of 90% or more. 20 Industrial applicability According to the present invention, since the hydrazide compound of the present invention has excellent efficacy of controlling pests, it is useful as an active ingredient of a 25 pesticide.

Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates.

Claims (2)

1. A compound represented by the formula (2-i) H O N-C--J (R 4)* (2-i ) C-NR 2 --NR 3 -H I I 0 wherein, R2 and R 3 independently represent a hydrogen atom, a C1-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 acyl group, a C2-C6 alkoxycarbonyl group, a C3-C7 N,N-dialkylcarbamoyl group, or a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group and (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, R4 represents a halogen atom, a cyano group, a nitro group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a phenyl group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom, or two R 4 groups 746 which are bound to the adjacent carbon atoms are bound at their terminal ends to each other to form a group Ti or T2 Tl: -CR 41 =CR 42 -CR 43 =CR- 4 4 _ T2: -(CR R")h (wherein R 4 1 , R 4 2 , R 43 and R" independently represent a hydrogen atom, a halogen atom, a cyano group, a nitro group, a Cl-C6 alkyl group optionally substituted with at least one halogen atom, a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom, or a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen.atom, R 4 5 and R 46 independently represent a hydrogen atom, or a Cl-C6 alkyl group optionally substituted with at least one halogen atom, and h represents an integer of 3 or 4), n represents an integer of 0 to 4 (provided that, when n is an integer of 2 or more, R Vs may be the same or different), J represents a group represented by Jl or J2: (R14a (14b Za _Ya (R 4)q J 1 : a J 2 : Z Rla (wherein Xa, ya, Za, Xb, yb and Zb independently represent CH or 747 a nitrogen atom, R1a and R"' represent a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a C2-C6 cyanoalkyl group; a C2-C6 alkoxyalkyl group optionally substituted with at least one halogen atom; a C2-C6 alkenyl group optionally substituted with at least one halogen atom; a C2-C6 alkynyl group optionally substituted with at least one halogen atom; a C3-C6 cycloalkyl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom and (2) a Cl-C6 alkyl group; a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom, (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, (6) a Cl-C6 alkylthio group optionally substituted with at least one halogen atom, (7) a Cl-C6 alkylsulfinyl group optionally substituted with at least one halogen atom and (8) a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom; a 5- to

6-membered heteroaryl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at 748 least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; a C7-C9 phenylalkyl group in whose benzene ring moiety may be substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; or a C7-C9 pyridinylalkyl group whose pyridine ring moiety may -be substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, R1 4 a and R1 4 b represent a halogen atom; a cyano group; a nitro group; an isocyanato group; a Cl-C6 alkyl group optionally substituted with at least one halogen atom; a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; a C2-C6 cyanoalkyloxy group; a C3-C6 alkoxyalkyloxy group optionally substituted with at least one halogen atom; a C3-C6 alkenyloxy group optionally substituted with at least one halogen atom; a C3-C6 alkynyloxy group optionally substituted with at least one halogen atom; a Cl-C6 alkylthio group optionally substituted with at least one halogen atom; a Cl-C6 749 alkylsulfinyl group optionally substituted with at least one halogen atom; a Cl-C6 alkylsulfonyl group optionally substituted with at least one halogen atom; a phenyl group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; a 5- to 6-membered heteroaryl group optionally substituted with one or more independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom; or a phenoxy group optionally substituted with 1 to 5 independent substituents selected from the group consisting of (1) a halogen atom, (2) a cyano group, (3) a nitro group, (4) a Cl-C6 alkyl group optionally substituted with at least one halogen atom and (5) a Cl-C6 alkoxy group optionally substituted with at least one halogen atom, p represents an integer of 0 to 3, and q represents an integer of 0 to 3 (provided that, when p is an integer of 2 or 3, two or more R1 4 1'S may be the same or different and, when q is an integer of 2 or 3, two or more R14b's 750 may be the same or different).