AU2013361514A1

AU2013361514A1 - Pesticidal compositions and processes related thereto

Info

Publication number: AU2013361514A1
Application number: AU2013361514A
Authority: AU
Inventors: Joshodeep BORUWA; James E. Hunter; Pravin S. IYER; William C. Lo; Akshay PATNY; Gerald B. Watson
Original assignee: Dow AgroSciences LLC
Current assignee: Corteva Agriscience LLC
Priority date: 2012-12-19
Filing date: 2013-12-18
Publication date: 2015-06-25
Anticipated expiration: 2033-12-18

Description

PESTICIDAL COMPOSITIONS AND PROCESSES RELATED THERETO

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Patent Application Serial No. 61/739,038 filed December 19, 2012, the entire disclosure of which is hereby expressly incorporated by reference.

FIELD OF THE DISCLOSURE

The invention disclosed in this document is related to the field of processes to produce molecules that are useful as pesticides (e.g., acaricides, insecticides, molluscicides, and nematicides), such molecules, and processes of using such molecules to control pests.

BACKGROUND OF THE DISCLOSURE

Pests cause millions of human deaths around the world each year. Furthermore, there are more than ten thousand species of pests that cause losses in agriculture. The world-wide agricultural losses amount to billions of U.S. dollars each year.

Termites cause damage to all kinds of private and public structures. The world-wide termite damage losses amount to billions of U.S. dollars each year.

Stored food pests eat and adulterate stored food. The world-wide stored food losses amount to billions of U.S. dollars each year, but more importantly, deprive people of needed food.

There is an acute need for new pesticides. Certain pests are developing resistance to pesticides in current use. Hundreds of pest species are resistant to one or more pesticides. The development of resistance to some of the older pesticides, such as DDT, the carbamates, and the organophosphates, is well known. But resistance has even developed to some of the newer pesticides, for example, imidacloprid.

Therefore, for many reasons, including the above reasons, a need exists for new pesticides.

DEFINITIONS

The examples given in the definitions are generally non-exhaustive and must not be construed as limiting the invention disclosed in this document. It is understood that a substituent should comply with chemical bonding rules and steric compatibility constraints in relation to the particular molecule to which it is attached.

"Alkenyl" means an acyclic, unsaturated (at least one carbon-carbon double bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, vinyl, allyl, butenyl, pentenyl, and hexenyl. "Alkenyloxy" means an alkenyl further consisting of a carbon-oxygen single bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.

"Alkoxy" means an alkyl further consisting of a carbon-oxygen single bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and ieri-butoxy.

"Alkyl" means an acyclic, saturated, branched or unbranched, substituent consisting of carbon and hydrogen, for example, methyl, ethyl, (C3)alkyl which represents n-propyl and isopropyl), (C₄)alkyl which represents n-butyl, sec-butyl, isobutyl, and ieri-butyl.

"Alkynyl" means an acyclic, unsaturated (at least one carbon-carbon triple bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, ethynyl, propargyl, butynyl, and pentynyl.

"Alkynyloxy" means an alkynyl further consisting of a carbon-oxygen single bond, for example, pentynyloxy, hexynyloxy, heptynyloxy, and octynyloxy.

"Aryl" means a cyclic, aromatic substituent consisting of hydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.

"(C_x-C_y)" where the subscripts "x" and "y" are integers such as 1, 2, or 3, means the range of carbon atoms for a substituent - for example, (Ci-C₄)alkyl means methyl, ethyl, n- propyl, isopropyl, n-butyl, sec -butyl, isobutyl, and ieri-butyl, each individually.

"Cycloalkenyl" means a monocyclic or polycyclic, unsaturated (at least one carbon- carbon double bond) substituent consisting of carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbornenyl, bicyclo[2.2.2]octenyl,

tetrahydronaphthyl, hexahydronaphthyl, and octahydronaphthyl.

"Cycloalkenyloxy" means a cycloalkenyl further consisting of a carbon-oxygen single bond, for example, cyclobutenyloxy, cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.

"Cycloalkyl" means a monocyclic or polycyclic, saturated substituent consisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.

"Cycloalkoxy" means a cycloalkyl further consisting of a carbon-oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbornyloxy, and

bicyclo[2.2.2]octyloxy.

"Halo" means fluoro, chloro, bromo, and iodo.

"Haloalkoxy" means an alkoxy further consisting of, from one to the maximum possible number of identical or different, halos, for example, fluoromethoxy, trifluoromethoxy, 2,2-difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,2,2- tetrafluoroethoxy, and pentafluoroethoxy.

"Haloalkyl" means an alkyl further consisting of, from one to the maximum possible number of, identical or different, halos, for example, fluoromethyl, trifluoromethyl, 2,2- difluoropropyl, chloromethyl, trichloromethyl, and 1,1,2,2-tetrafluoroethyl.

"Heterocyclyl" means a cyclic substituent that may be fully saturated, partially unsaturated, or fully unsaturated, where the cyclic structure contains at least one carbon and at least one heteroatom, where said heteroatom is nitrogen, sulfur, or oxygen. In the case of sulfur, that atom can be in other oxidation states such as a sulfoxide and sulfone. Examples of aromatic heterocyclyls include, but are not limited to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, cinnolinyl, furanyl, imidazolyl, indazolyl, indolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, and triazolyl. Examples of fully saturated heterocyclyls include, but are not limited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, tetrahydrothienyl and tetrahydropyranyl. Examples of partially unsaturated heterocyclyls include, but are not limited to, 1,2,3,4-tetrahydroquinolinyl, 4,5-dihydro-oxazolyl, 4,5- dihydro-lH-pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[l,3,4]-oxadiazolyl.

Addition

thietanyl thietanyl-oxide thietanyl-dioxide.

DETAILED DESCRIPTION OF THE DISCLOSURE

This document disc ("Formula One"):

Formula One wherein:

(a) Rl is selected from

(1) H, F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), S(0)(C C₈)alkyl, S(0)(halo(Ci-C₈)alkyl), S(0)₂(C C₈)alkyl, S(0)₂(halo(C C₈)alkyl), N(R14)(R15),

(2) substituted (Ci-C₈)alkyl, wherein said substituted (Ci-C₈)alkyl has one or more substituents selected from CN and N0₂,

(3) substituted halo(Ci-C₈)alkyl, wherein said substituted halo(C C₈)alkyl, has one or more substituents selected from CN and N0₂,

(4) substituted (Ci-C₈)alkoxy, wherein said substituted (Ci-C₈)alkoxy has one or more substituents selected from CN and N0₂, and

(5) substituted halo(Ci-C₈)alkoxy, wherein said substituted halo(Ci- C₈)alkoxy has one or more substituents selected from CN and N0₂;

(b) R2 is selected from

(3) substituted halo(Ci-C₈)alkyl, wherein said substituted halo(d- C₈)alkyl, has one or more substituents selected from CN and N0₂,

(4) substituted (Ci-C₈)alkoxy, wherein said substituted (C C₈)alkoxy has one or more substituents selected from CN and N0₂, and

(c) R3 is selected from

(3) substituted halo(Ci-C₈)alkyl, wherein said substituted halo(d- C₈)alkyl, has one or more substituents selected from CN and N0₂, (4) substituted (Ci-Cs)alkoxy, wherein said substituted (Ci-C₈)alkoxy has one or more substituents selected from CN and N0₂, and

(5) substituted halo(Ci-Cs)alkoxy, wherein said substituted halo(Ci- C₈)alkoxy has one or more substituents selected from CN and N0₂;

(d) R4 is selected from

(1) H, F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), S(0)(C C₈)alkyl, S(0)(halo(C C₈)alkyl), S(0)₂(C C₈)alkyl, S(0)₂(halo(C C₈)alkyl), N(R14)(R15),

(4) substituted (Ci-Cs)alkoxy, wherein said substituted (Ci-C₈)alkoxy has one or more substituents selected from CN and N0₂, and

(5) substituted halo(Ci-Cs)alkoxy, wherein said substituted halo(d-

C₈)alkoxy has one or more substituents selected from CN and N0₂;

(e) R5 is selected from

(f) R6 is a (Ci-C₈)haloalkyl;

(g) R7 is selected from H, F, CI, Br, I, OH, (C C₈)alkoxy, and halo(C

C₈)alkoxy;

(h) R8 is selected from H, (C C₈)alkyl, halo(C C₈)alkyl, OR14, and

N(R14)(R15); (i) R9 is selected from H, F, CI, Br, I, (C C₈)alkyl, halo(C C₈)alkyl, (C

C₈)alkoxy, halo(C C₈)alkoxy, OR14, and N(R14)(R15);

(j) RIO is selected from

(1) H, F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C

C₈)alkoxy, halo(C C₈)alkoxy, cyclo(C₃-C₆)alkyl, S(C C₈)alkyl, S(halo(C C₈)alkyl), S(0)(C C₈)alkyl, S(0)(halo(C C₈)alkyl), S(0)₂(C C₈)alkyl, S(0)₂(halo(C C₈)alkyl), NR14R15, C(=0)H, C(=0)N(R14)(R15), CN(R14)(R15)(=NOH), (C=0)0(C C₈)alkyl, (C=0)OH, heterocyclyl, (C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl, (C₂-C₈)alkynyl,

(2) substituted (Ci-C₈)alkyl, wherein said substituted (Ci-C₈)alkyl has one or more substituents selected from OH, (Ci-C₈)alkoxy, S(Ci-C₈)alkyl, S(0)(Ci-C₈)alkyl,

S(0)₂(Ci-C₈)alkyl, NR14R15, and

(3) substituted halo(Ci-C₈)alkyl, wherein said substituted halo(d- C₈)alkyl, has one or more substituents selected from (Ci-C₈)alkoxy, S(Ci-C₈)alkyl, S(0)(Cr C₈)alkyl, S(0)₂(C C₈)alkyl, and N(R14)(R15);

(k) Rll is C(=X5)N(H)((Co-C₈)alkyl)N(Rlla)(C(=X5)(Rl lb))

wherein each X5 is independently selected from O or S, and

wherein each Rlla is independently selected from H, (Ci-C₈)alkyl, substituted (Ci-C₈)alkyl, halo(C C₈)alkyl, substituted halo(C C₈)alkyl, cyclo(C₃-C₈)alkyl, and substituted cyclo(C3-C₈)alkyl,

wherein each said substituted (Ci-C₈)alkyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, OC(=0)H, OH, S(Ci-C₈)alkyl, S(0)(C C₈)alkyl, S(0)₂(C C₈)alkyl, OS(0)₂aryl, N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, wherein each said substituted aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (Q- C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), N((Ci-C₈)alkyl)₂ (wherein each (Ci-C₈)alkyl is independently selected), and oxo, wherein each said substituted heterocyclyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), C(=0)(C C₈)alkyl, C(=0)(C₃-C₆)cycloalkyl, S(=0)₂(C C₈)alkyl, NR14R15, and oxo, wherein each said substituted-aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (Ci-C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C

C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo, wherein said substituted halo(Ci-C₈)alkyl, has one or more substituents selected from CN and N0₂,

wherein said substituted cyclo(C₃-C₈)alkyl, has one or more substituents selected from CN and N0₂

wherein each Rl lb is independently selected from (Ci-C₈)alkyl, substituted (Cr

C₈)alkyl, halo(Ci-C₈)alkyl, substituted halo(Ci-C₈)alkyl, cyclo(C₃-C₈)alkyl, substituted cyclo(C₃-C₈)alkyl, (C₂-C₈)alkenyl, and (C₂-C₈)alkynyl,

wherein each said substituted (Ci-C₈)alkyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, OC(=0)H, OH, S(Ci-C₈)alkyl, S(0)(C C₈)alkyl, S(0)₂(Ci-C₈)alkyl, OS(0)₂aryl, N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, wherein each said substituted aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (Q- C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), N((Ci-C₈)alkyl)₂ (wherein each (Ci-C₈)alkyl is independently selected), and oxo, wherein each said substituted heterocyclyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), C(=0)(C C₈)alkyl, C(=0)(C₃-C₆)cycloalkyl, S(=0)₂(C C₈)alkyl, NR14R15, and oxo, wherein each said substituted-aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (Ci-C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C

C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo,

wherein said substituted halo(Ci-C₈)alkyl, has one or more substituents selected from CN and N0₂,

wherein said substituted cyclo(C3-C₈)alkyl, has one or more substituents selected from CN and N0₂;

(1) R12 is selected from (v), H, F, CI, Br, I, CN, (C C₈)alkyl, halo(C C₈)alkyl, (Ci-C₈)alkoxy, halo(Ci-C₈)alkoxy, and cyclo(C₃-C6)alkyl;

(m) R13 is selected from (v), H, F, CI, Br, I, CN, (C C₈)alkyl, halo(C C₈)alkyl, (Ci-C₈)alkoxy, and halo(Ci-C₈)alkoxy;

(n) each R14 is independently selected from H, (Ci-C₈)alkyl, (C2-C8)alkenyl, substituted (Ci-C₈)alkyl, halo(Ci-C₈)alkyl, substituted halo(Ci-C₈)alkyl), (Ci-C₈)alkoxy, cyclo(C₃-C6)alkyl, aryl, substituted-aryl, (Ci-C₈)alkyl-aryl, (Ci-C₈)alkyl-(substituted-aryl), O- (Ci-C₈)alkyl-aryl, 0-(Ci-C₈)alkyl-(substituted-aryl), heterocyclyl, substituted-heterocyclyl, (C C₈)alkyl-heterocyclyl, (C C₈)alkyl-(substituted-heterocyclyl), 0-(C C₈)alkyl- heterocyclyl, 0-(C C₈)alkyl-(substituted-heterocyclyl), N(R16)(R17), (C C₈)alkyl- C(=0)N(R16)(R17), C(=0)(C C₈)alkyl, C(=0)(halo(Ci-C₈)alkyl),C(=0)(C₃-C₆)cycloalkyl, (Ci-C₈)alkyl-C(=0)0(Ci-C₈)alkyl, C(=0)H

wherein each said substituted (Ci-C₈)alkyl has one or more substituents selected from CN, and N0₂,

wherein each said substituted halo(C]-C₈)alkyl), has one or more substituents selected from CN, and N0₂,

wherein each said substituted- aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(Ci-C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo, and

wherein each said substituted-heterocyclyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, (C₃-C₆)cycloalkyl S(C C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (Ci-C₈)alkyl is independently selected), heterocyclyl, C(=0)(C C₈)alkyl, C(=0)0(C C₈)alkyl, and oxo, (wherein said alkyl, alkoxy, and heterocyclyl, may be further substituted with one or more of F, CI, Br, I, CN, and N0₂);

(o) each R15 is independently selected from H, (Ci-C₈)alkyl, (C2-C8)alkenyl, substituted (C C₈)alkyl, halo(C C₈)alkyl, substituted halo(C C₈)alkyl), (C C₈)alkoxy, cyclo(C3-C6)alkyl, aryl, substituted-aryl, (Ci-C₈)alkyl-aryl, (Ci-C₈)alkyl-(substituted-aryl), O- (C]-C₈)alkyl-aryl, 0-(Ci-C₈)alkyl-(substituted-aryl), heterocyclyl, substituted-heterocyclyl, (Ci-C₈)alkyl-heterocyclyl, (C C₈)alkyl-(substituted-heterocyclyl), 0-(C C₈)alkyl- heterocyclyl, 0-(C C₈)alkyl-(substituted-heterocyclyl), N(R16)(R17), (C C₈)alkyl- C(=0)N(R16)(R17), C(=0)(C C₈)alkyl, C(=0)(halo(C C₈)alkyl), C(=0)(C₃-C₆)cycloalkyl, (Ci-C₈)alkyl-C(=0)0(Ci-C₈)alkyl, C(=0)H

wherein each said substituted halo(Ci-C₈)alkyl), has one or more substituents selected from CN, and N0₂,

wherein each said substituted-aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(Ci-C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo, and wherein each said substituted-heterocyclyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, (C₃-C₆)cycloalkyl S(C C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (Ci-C₈)alkyl is independently selected), heterocyclyl, C(=0)(C C₈)alkyl, C(=0)0(C C₈)alkyl, and oxo, (wherein said alkyl, alkoxy, and heterocyclyl, may be further substituted with one or more of F, CI, Br, I, CN, and N0₂);

(p) each R16 is independently selected from H, (C]-C₈)alkyl, substituted-(Cr C₈)alkyl, halo(C]-C₈)alkyl, substituted-halo(Ci-C₈)alkyl, cyclo(C3-C6)alkyl, aryl, substituted- aryl, (C C₈)alkyl-aryl, (C C₈)alkyl-(substituted-aryl), 0-(C C₈)alkyl-aryl, 0-(C C₈)alkyl- (substituted-aryl), heterocyclyl, substituted-heterocyclyl, (Ci-C₈)alkyl-heterocyclyl, (Cr C₈)alkyl-(substituted-heterocyclyl), 0-(C C₈)alkyl-heterocyclyl, 0-(C C₈)alkyl- (substituted-heterocyclyl), 0-(Ci-C₈)alkyl

wherein each said substituted-aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(Ci-C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo, and

wherein each said substituted-heterocyclyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo;

(q) each R17 is independently selected from H, (C C₈)alkyl, substituted-(C

C₈)alkyl, halo(Ci-C₈)alkyl, substituted-halo(Ci-C₈)alkyl, cyclo(C3-C6)alkyl, aryl, substituted- aryl, (Ci-C₈)alkyl-aryl, (C C₈)alkyl-(substituted-aryl), 0-(C C₈)alkyl-aryl, 0-(C C₈)alkyl- (substituted-aryl), heterocyclyl, substituted-heterocyclyl, (Ci-C₈)alkyl-heterocyclyl, (Cr C₈)alkyl-(substituted-heterocyclyl), 0-(C C₈)alkyl-heterocyclyl, 0-(C C₈)alkyl- (substituted-heterocyclyl), 0-(C C₈)alkyl

wherein each said substituted halo(Ci-C₈)alkyl), has one or more substituents selected from CN, and N0₂, wherein each said substituted- aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(Ci-C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo, and

(r) XI is selected from N and CR12;

(s) X2 is selected from N, CR9, and CR13;

(t) X3 is selected from N and CR9; and

(v) R12 and R13 together form a linkage containing 3 to 4 atoms selected from C, N, O, and S, wherein said linkage connects back to the ring to form a 5 to 6 member saturated or unsaturated cyclic ring, wherein said linkage has at least one substituent X4 wherein X4 is selected from R14, N(R14)(R15), N(R14)(C(=0)R14), N(R14)(C(=S)R14),

N(R14)(C(=0)N(R14)(R14)), N(R14)(C(=S)N(R14)(R14)), N(R14)(C(=0)N(R14)((C2- C8)alkenyl)), N(R14)(C(=S)N(R14)((C2-C8)alkenyl)), wherein each R14 is independently selected.

In another embodiment of this invention Rl may be selected from any combination of one or more of the following - H, F, CI, Br, I, CN, N0₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C₆)alkyl, halo(C7)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy, (C₆)alkoxy, (C7)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C₆)alkoxy, halo(C7)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R2 may be selected from any combination of one or more of the following - H, F, CI, Br, I, CN, N0₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C6)alkyl, halo(C7)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy, (C₆)alkoxy, (C7)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C3)alkoxy, halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C₆)alkoxy, halo(C7)alkoxy, and halo(C₈)alkoxy.

In another embodiment of this invention R3 may be selected from any combination of one or more of the following - H, F, CI, Br, I, CN, N0₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C₆)alkyl, halo(C7)alkyl, halo(Cs)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (Cs)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(Cs)alkoxy.

In another embodiment of this invention R4 may be selected from any combination of one or more of the following - H, F, CI, Br, I, CN, N0₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(Cs)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (Cs)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(Cs)alkoxy.

In another embodiment of this invention R5 may be selected from any combination of one or more of the following - H, F, CI, Br, I, CN, N0₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(Cs)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (Cs)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(Cs)alkoxy.

In another embodiment of this invention R2 and R4 are selected from F, CI, Br, I, CN, and N0₂ and Rl, R3, and R5 are H.

In another embodiment of this invention R2, R3, and R4 are selected from F, CI, Br, I, CN, and N0₂ and Rl, and R5 are H.

In another embodiment of this invention R2, R3, and R4 are independently selected from F and CI and Rland R5 are H.

In another embodiment of this invention Rl is selected from CI and H.

In another embodiment of this invention R2 is selected from CF₃, CH₃, CI, F, and H. In another embodiment of this invention R3 is selected from OCH₃, CH₃, F, CI, or H. In another embodiment of this invention R4 is selected from CF₃, CH₃, CI, F, and H. In another embodiment of this invention R5 is selected from F, CI, and H.

In another embodiment of this invention R6 may be selected from any combination of one or more of the following - halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, and halo(C₈)alkyl.

In another embodiment of this invention R6 is trifluoromethyl. In another embodiment of this invention R7 may be selected from any combination of one or more of the following - H, F, CI, Br, and I.

In another embodiment of this invention R7 is selected from H, OCH₃, and OH.

In another embodiment of this invention R8 may be selected from any combination of one or more of the following - H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, and halo(C₈)alkyl.

In another embodiment of this invention R8 is selected from CH₃ and H.

In another embodiment of this invention R9 may be selected from any combination of one or more of the following - H, F, CI, Br, I, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(Cs)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (Cs)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(Cs)alkoxy.

In another embodiment of this invention RIO may be selected from any combination of one or more of the following - H, F, CI, Br, I, CN, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(Cs)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (Cs)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, halo(Cs)alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

In another embodiment of this invention R10 may be selected from any combination of one or more of the following - H, CI, Br, CH₃, and CF₃.

In another embodiment of this invention R10 is selected from Br, C(=NOH)NH₂,

C(=0)H, C(=0)NH₂, C(=0)OCH₂CH₃, C(=0)OH, CF₃, CH₂CH₃, CH₂OH, CH3, CI, CN, F, H, NH₂, NHC(=0)H, NHCH₃, N0₂, OCH₃, OCHF₂, and pyridyl.

In another embodiment Rl l is C(=(0 or S))N(H)N(H)(C(=(0 or S))(halo(C

C₈)alkyl))

In another embodiment of this invention R12 may be selected from any combination of one or more of the following - H, F, CI, Br, I, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(Cs)alkyl, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C4)alkoxy, halo(Cs)alkoxy, halo(C6)alkoxy, halo(C7)alkoxy, and halo(Cs)alkoxy.

In another embodiment of this invention R12 is selected from CH3, and H.

In another embodiment of this invention R13 may be selected from any combination of one or more of the following - H, F, CI, Br, I, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C₆)alkyl, halo(C7)alkyl, halo(Cs)alkyl, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C6)alkoxy, halo(C7)alkoxy, and halo(Cs)alkoxy.

In another embodiment of this invention R13 is selected from CH₃, CI and H.

In another embodiment of this invention R12-R13 are a hydrocarbyl linkage containing CH=CHCH=CH.

In another embodiment of this invention R14 may be selected from any combination of one or more of the following - H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl- aryl, (Cs)alkyl-aryl, (C6)alkyl-aryl, (C7)alkyl-aryl, (Cs)alkyl-aryl, methyl-(substituted-aryl), ethyl-(substituted-aryl), (C₃)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (Cs)alkyl- (substituted-aryl), (C6)alkyl-(substituted-aryl), (C7)alkyl-(substituted-aryl), (Cs)alkyl- (substituted-aryl), O-methyl-aryl, O-ethyl-aryl, 0-(C₃)alkyl-aryl, 0-(C₄)alkyl-aryl, O-

(C₅)alkyl-aryl, 0-(C₆)alkyl-aryl, 0-(C₇)alkyl-aryl, 0-(C₈)alkyl-aryl, 0-methyl-(substituted- aryl), O-ethyl-(substituted-aryl), 0-(C₃)alkyl-(substituted-aryl), 0-(C₄)alkyl-(substituted- aryl), 0-(C₅)alkyl-(substituted-aryl), 0-(C₆)alkyl-(substituted-aryl), 0-(C₇)alkyl-(substituted- aryl), 0-(Cs)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C₃)alkyl- heterocyclyl, (C₄)alkyl-heterocyclyl, (Cs)alkyl-heterocyclyl, (C6)alkyl-heterocyclyl,

(C7)alkyl-heterocyclyl, (Cs)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl- (substituted-heterocyclyl), (C₃)alkyl-(substituted-heterocyclyl), (C₄)alkyl-(substituted- heterocyclyl), (Cs)alkyl-(substituted-heterocyclyl), (C6)alkyl-(substituted-heterocyclyl), (C7)alkyl-(substituted-heterocyclyl), (Cs)alkyl-(substituted-heterocyclyl), O-methyl- heterocyclyl, O-ethyl-heterocyclyl, 0-(C₃)alkyl-heterocyclyl, 0-(C₄)alkyl-heterocyclyl, O- (C₅)alkyl-heterocyclyl, 0-(C₆)alkyl-heterocyclyl, 0-(C₇)alkyl-heterocyclyl, 0-(C₈)alkyl- heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O- (C₃)alkyl-(substituted-heterocyclyl), 0-(C₄)alkyl-(substituted-heterocyclyl), 0-(Cs)alkyl- (substituted-heterocyclyl), 0-(C6)alkyl-(substituted-heterocyclyl), 0-(C7)alkyl-(substituted- heterocyclyl), 0-(C₈)alkyl-(substituted-heterocyclyl), methyl-C(=0)N(R16)(R17), ethyl- C(=0)N(R16)(R17), (C₃)alkyl-C(=0)N(R16)(R17), (C₄)alkyl-C(=0)N(R16)(R17), (C₅)alkyl- C(=0)N(R16)(R17), (C₆)alkyl-C(=0)N(R16)(R17), (C₇)alkyl-C(=0)N(R16)(R17), and (C₈)alkyl-C(=0)N(R16)(R17).

In another embodiment of this invention R14 may be selected from any combination of one or more of the following - H, CH₃, CH₂CF₃, C]¾-halopyridyl, oxo-pyrrolidinyl, halophenyl, thietanyl, CH₂-phenyl, CH₂-pyridyl, thietanyl-dioxide, CH₂-halothiazolyl, C((CH₃)₂)-pyridyl, N(H) (halophenyl), CH₂-pyrimidinyl, CH₂-tetrahydrofuranyl, CH₂-furanyl, 0-CH₂-halopyridyl, and CH₂C(=0)N(H)(CH₂CF₃).

In another embodiment of this invention R15 may be selected from any combination of one or more of the following - H, methyl, ethyl, (C3)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl- aryl, (Cs)alkyl-aryl, (C6)alkyl-aryl, (C7)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl), ethyl-(substituted-aryl), (C3)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (Cs)alkyl- (substituted-aryl), (C6)alkyl-(substituted-aryl), (C7)alkyl-(substituted-aryl), (C₈)alkyl- (substituted-aryl), O-methyl-aryl, O-ethyl-aryl, 0-(C3)alkyl-aryl, 0-(C₄)alkyl-aryl, O- (C₅)alkyl-aryl, 0-(C₆)alkyl-aryl, 0-(C₇)alkyl-aryl, 0-(C₈)alkyl-aryl, 0-methyl-(substituted- aryl), O-ethyl-(substituted-aryl), 0-(C3)alkyl-(substituted-aryl), 0-(C₄)alkyl-(substituted- aryl), 0-(C₅)alkyl-(substituted-aryl), 0-(C₆)alkyl-(substituted-aryl), 0-(C₇)alkyl-(substituted- aryl), 0-(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C3)alkyl- heterocyclyl, (C₄)alkyl-heterocyclyl, (Cs)alkyl-heterocyclyl, (C6)alkyl-heterocyclyl,

(C7)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl- (substituted-heterocyclyl), (C3)alkyl-(substituted-heterocyclyl), (C₄)alkyl-(substituted- heterocyclyl), (Cs)alkyl-(substituted-heterocyclyl), (C6)alkyl-(substituted-heterocyclyl), (C7)alkyl-(substituted-heterocyclyl), (C₈)alkyl-(substituted-heterocyclyl), O-methyl- heterocyclyl, O-ethyl-heterocyclyl, 0-(C3)alkyl-heterocyclyl, 0-(C₄)alkyl-heterocyclyl, O- (C₅)alkyl-heterocyclyl, 0-(C₆)alkyl-heterocyclyl, 0-(C₇)alkyl-heterocyclyl, 0-(C₈)alkyl- heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O- (C₃)alkyl-(substituted-heterocyclyl), 0-(C₄)alkyl-(substituted-heterocyclyl), 0-(C₅)alkyl- (substituted-heterocyclyl), 0-(C6)alkyl-(substituted-heterocyclyl), 0-(C7)alkyl-(substituted- heterocyclyl), 0-(C₈)alkyl-(substituted-heterocyclyl), methyl-C(=0)N(R16)(R17), ethyl- C(=0)N(R16)(R17), (C₃)alkyl-C(=0)N(R16)(R17), (C₄)alkyl-C(=0)N(R16)(R17), (C₅)alkyl- C(=0)N(R16)(R17), (C₆)alkyl-C(=0)N(R16)(R17), (C₇)alkyl-C(=0)N(R16)(R17), and (C₈)alkyl-C(=0)N(R16)(R17).

In another embodiment of this invention R15 may be selected from any combination of one or more of the following - H, C¾, CH₂CF₃, CH₂-halopyridyl, oxo-pyrrolidinyl, halophenyl, thietanyl, CH₂-phenyl, CH₂-pyridyl, thietanyl-dioxide, CH₂-halothiazolyl,

C((CH₃)₂)-pyridyl, N(H) (halophenyl), CH₂-pyrimidinyl, CH₂-tetrahydrofuranyl, CH₂-furanyl, 0-CH₂-halopyridyl, and CH₂C(=0)N(H)(CH₂CF₃).

In another embodiment of this invention R16 may be selected from any combination of one or more of the following - H, methyl, ethyl, (C3)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl- aryl, (Cs)alkyl-aryl, (C6)alkyl-aryl, (C7)alkyl-aryl, (Cs)alkyl-aryl, methyl-(substituted-aryl), ethyl-(substituted-aryl), (C3)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (Cs)alkyl- (substituted-aryl), (C6)alkyl-(substituted-aryl), (C7)alkyl-(substituted-aryl), (Cs)alkyl- (substituted-aryl), O-methyl-aryl, O-ethyl-aryl, 0-(C3)alkyl-aryl, 0-(C₄)alkyl-aryl, O-

(C₅)alkyl-aryl, 0-(C₆)alkyl-aryl, 0-(C₇)alkyl-aryl, 0-(C₈)alkyl-aryl, 0-methyl-(substituted- aryl), O-ethyl-(substituted-aryl), 0-(C3)alkyl-(substituted-aryl), 0-(C₄)alkyl-(substituted- aryl), 0-(C₅)alkyl-(substituted-aryl), 0-(C₆)alkyl-(substituted-aryl), 0-(C₇)alkyl-(substituted- aryl), 0-(Cs)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C3)alkyl- heterocyclyl, (C₄)alkyl-heterocyclyl, (Cs)alkyl-heterocyclyl, (C6)alkyl-heterocyclyl,

(C7)alkyl-heterocyclyl, (Cs)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl- (substituted-heterocyclyl), (C3)alkyl-(substituted-heterocyclyl), (C₄)alkyl-(substituted- heterocyclyl), (Cs)alkyl-(substituted-heterocyclyl), (C6)alkyl-(substituted-heterocyclyl), (C7)alkyl-(substituted-heterocyclyl), (Cs)alkyl-(substituted-heterocyclyl), O-methyl- heterocyclyl, O-ethyl-heterocyclyl, 0-(C3)alkyl-heterocyclyl, 0-(C₄)alkyl-heterocyclyl, O- (C₅)alkyl-heterocyclyl, 0-(C₆)alkyl-heterocyclyl, 0-(C₇)alkyl-heterocyclyl, 0-(C₈)alkyl- heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O- (C3)alkyl-(substituted-heterocyclyl), 0-(C₄)alkyl-(substituted-heterocyclyl), 0-(Cs)alkyl- (substituted-heterocyclyl), 0-(C6)alkyl-(substituted-heterocyclyl), 0-(C7)alkyl-(substituted- heterocyclyl), and 0-(Cs)alkyl-(substituted-heterocyclyl).

In another embodiment of this invention R16 may be selected from any combination of one or more of the following - H, CH₂CF₃, cyclopropyl, thietanyl, thietanyl dioxide, and halophenyl. In another embodiment of this invention R17 may be selected from any combination of one or more of the following - H, methyl, ethyl, (C3)alkyl, (C₄)alkyl, (Cs)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl- aryl, (Cs)alkyl-aryl, (C6)alkyl-aryl, (C7)alkyl-aryl, (Cs)alkyl-aryl, methyl-(substituted-aryl), ethyl-(substituted-aryl), (C3)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (Cs)alkyl- (substituted-aryl), (C6)alkyl-(substituted-aryl), (C7)alkyl-(substituted-aryl), (Cs)alkyl- (substituted-aryl), O-methyl-aryl, O-ethyl-aryl, 0-(C3)alkyl-aryl, 0-(C₄)alkyl-aryl, O- (C₅)alkyl-aryl, 0-(C₆)alkyl-aryl, 0-(C₇)alkyl-aryl, 0-(C₈)alkyl-aryl, 0-methyl-(substituted- aryl), O-ethyl-(substituted-aryl), 0-(C3)alkyl-(substituted-aryl), 0-(C₄)alkyl-(substituted- aryl), 0-(C₅)alkyl-(substituted-aryl), 0-(C₆)alkyl-(substituted-aryl), 0-(C₇)alkyl-(substituted- aryl), 0-(Cs)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C3)alkyl- heterocyclyl, (C₄)alkyl-heterocyclyl, (Cs)alkyl-heterocyclyl, (C6)alkyl-heterocyclyl, (C7)alkyl-heterocyclyl, (Cs)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl- (substituted-heterocyclyl), (C3)alkyl-(substituted-heterocyclyl), (C₄)alkyl-(substituted- heterocyclyl), (Cs)alkyl-(substituted-heterocyclyl), (C6)alkyl-(substituted-heterocyclyl), (C7)alkyl-(substituted-heterocyclyl), (Cs)alkyl-(substituted-heterocyclyl), O-methyl- heterocyclyl, O-ethyl-heterocyclyl, 0-(C3)alkyl-heterocyclyl, 0-(C₄)alkyl-heterocyclyl, O- (C₅)alkyl-heterocyclyl, 0-(C₆)alkyl-heterocyclyl, 0-(C₇)alkyl-heterocyclyl, 0-(C₈)alkyl- heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O- (C3)alkyl-(substituted-heterocyclyl), 0-(C₄)alkyl-(substituted-heterocyclyl), 0-(Cs)alkyl- (substituted-heterocyclyl), 0-(C6)alkyl-(substituted-heterocyclyl), 0-(C7)alkyl-(substituted- heterocyclyl), and 0-(Cs)alkyl-(substituted-heterocyclyl).

In another embodiment of this invention R17 may be selected from any combination of one or more of the following - H, CH₂CF₃, cyclopropyl, thietanyl, thietanyl dioxide, and halophenyl.

In another embodiment of this invention XI is CR12, X2 is CR13, and X3 is CR9.

In another embodiment of this invention a heterocyclyl has preferably about 6 to 10 atoms in the ring structure, more preferably, 6 to 8 atoms.

The molecules of Formula One will generally have a molecular mass of about 100

Daltons to about 1200 Daltons. However, it is generally preferred if the molecular mass is from about 120 Daltons to about 900 Daltons, and it is even more generally preferred if the molecular mass is from about 140 Daltons to about 600 Daltons. The benzyl alcohol of Formula IV, wherein Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, can be synthesized in two ways. One way, disclosed in step a of Scheme I, is by treatment of the ketone of Formula II, wherein Rl, R2, R3, R4, R5, and R6 are as previously disclosed, with a reducing agent, such as sodium borohydride (NaBH₄), under basic conditions, such as aqueous sodium hydroxide (NaOH), in a polar pro tic solvent, such as methanol (MeOH) at 0 °C. Alternatively, an aldehyde of Formula III, wherein Rl, R2, R3, R4, R5, and R7 are as previously disclosed, is allowed to react with

trifluorotrimethylsilane in the presence of a catalytic amount of tetrabutylammonium fluoride in a polar aprotic solvent, such as tetrahydrofuran (THF), as in step b of Scheme I. The compound of Formula IV can be transformed into the compound of Formula V, wherein Y is selected from Br, CI or I, and Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, by reaction with a halogenating reagent, such as N-bromosuccinimide and triethyl phosphite in a non-reactive solvent, such as dichloromethane (CH₂CI₂) at reflux temperature to provide Y = Br, or such as thionyl chloride and pyridine in a hydrocarbon solvent, such as toluene at reflux temperature to provide Y = CI, as in step c of Scheme I.

Scheme I

III

Formation of the styrene coupling partners can be accomplished as in Schemes II, III IV and V.

In Scheme II, a vinylbenzoic acid of Formula VI, wherein Rl l is (C=0)OH and R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, can be converted in two steps to the vinylbenzamide of Formula Vila, wherein Rl l is (C=0)N(R14)(R15), and R8, R9, RIO, R12, R13, R14, R15, and X are as previously disclosed. As in step d of Scheme II, the benzoic acid of Formula VI is treated with oxalyl chloride in the presence of a catalytic amount of N,N-dimethylformamide (DMF) in a non-reactive solvent such as CH₂CI₂ to form the acid chloride, which is subsequently allowed to react with an amine (HN(R14)(R15)), wherein R14 and R15 are as previously disclosed, in the presence of a base, such as triethylamine (TEA), in a polar aprotic solvent, such as THF, to provide the vinyl benzamide of Formula Vila, wherein Rl l is (C=0)N(R14)(R15), and R8, R9, RIO, R12, R13, R14, R15, XI, X2, and X3 are as previously disclosed, as in step e of Scheme II.

Scheme II

VI Vila

In Schemes III and IV, a halobenzoic acid of Formula VIII, wherein R18 is Br or I, Rl l is (C=0)OH and R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed can be converted to a vinylbenzoic acid ester of Formula Vllbl or Formula VIIb2, wherein R18 is Br or I, Rl l is (C=0)0(C C₆ alkyl), and R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed. In step / of Scheme III, the halobenzoic acid of Formula VIII, wherein R18 is Br, is treated with a base, such as n-butyllithium (n-BuLi), and DMF in a polar, aprotic solvent, such as THF, at a temperature of about -78 °C. The resulting formyl benzoic acid is allowed to react with an acid, such as sulfuric acid (H₂SO₄), in the presence of an alcohol, such as ethyl alcohol (EtOH), as in step g, to provide the formyl benzoic acid ethyl ester of Formula IX, wherein Rl l is (C=0)0(C C₆ alkyl), and R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed. The vinyl benzoic acid ester of Formula Vllbl is accessed via reaction of the compounds of Formula IX, with a base, such as potassium carbonate (K₂CO₃), and methyl triphenyl phosphonium bromide in a polar aprotic solvent, such as 1 ,4-dioxane, at ambient temperature, as in step h of Scheme III. Scheme III

VIII IX Vllbl

In step i of Scheme IV, the halobenzoic acid of Formula VIII, wherein R18 is Br, Rl 1 is (C=0)OH, and R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, is treated with di-ieri-butyl dicarbonate in the presence of a base, such as TEA and a catalytic amount of 4-(dimethylamino)pyridine (DMAP) in a polar aprotic solvent, such as THF, at ambient temperature. The resulting benzoic acid ieri-butyl ester is allowed to react with vinyl boronic anhydride pyridine complex in the presence of a palladium catalyst, such a tetrakis(triphenylphospine)palladium(0) (Pd(PPh3)₄), and a base, such as K2CO₃, in a non- reactive solvent such as toluene at reflux temperature, as in step j, to provide the vinyl benzoic acid ester of Formula VIIb2, wherein Rll is (C=0)0(C C₆ alkyl), and R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed.

Scheme IV

VIII VIIb2

In step k of Scheme V, the vinyl benzoic acid ester of Formula VIIb2, wherein RIO is Br, Rll is (C=0)0(C C₆ alkyl), and R8, R9, R12, R13, XI, X2, and X3 are as previously defined, can be further transformed into the corresponding vinyl benzoic acid ester of Formula VIIb3, wherein RIO is CN, Rll is (C=0)0(C C₆ alkyl), and R8, R9, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with copper(I) cyanide (CuCN) in a polar aprotic solvent, such as DMF, at 140 °C. Scheme V

Vllb2 Vllb3

Coupling of the compounds of Formula V with the compounds of Formula Vila, Vllbl , VIIb2 and VIIb3 can be accomplished as in Schemes VI, VII, and VIII. In step I of Scheme VI, a compound of Formula V, wherein Y, Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzamide of Formula Vila, wherein Rl 1 is

(C=0)N(R14)(R15), and R8, R9, RIO, R12, R13, R14, R15, XI, X2, and X3 are as previously disclosed, are allowed to react in the presence of copper(I) chloride (CuCl) and 2,2-bipyridyl in a solvent, such as 1 ,2-dichlorobenzene, at a temperature of about 180 °C to provide the molecules of Formula One, wherein Rl l is (C=0)N(R14)(R15), and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, XI , X2, and X3 are as previously disclosed.

Scheme VI

V Vila Formula One

In step I of Scheme VII, the compound of Formula V, wherein Y, Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzoic acid ester of Formula Vllbl, wherein Rl 1 is (C=0)0(C C₆ alkyl), and R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1 ,2-dichlorobenzene, at a temperature of about 180 °C to provide the compounds of Formula Xa, wherein Rl 1 is (C=0)0(C C₆ alkyl), and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed. The compounds of Formula Xa are then converted to the molecules of Formula One, wherein Rl 1 is

(C=0)N(R14)(R15), and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, XI, X2, and X3 are as previously disclosed, by either a two-step process as disclosed in steps m and n or in one step as disclosed in step o. In step m of Scheme VII, the ester of Formula Xa is saponified to the corresponding acid under acidic conditions, such as about 11 Normal (N) hydrochloric acid (HCl), in a polar aprotic solvent, such as 1 ,4-dioxane, at about 100 °C. The acid can subsequently be coupled to an amine (HN(R14)(R15)), wherein R14 and R15 are as previously disclosed using peptide coupling reagents, such as 1-hydroxybenzotriazole (HOBt), N-(3-dimethylaminopropyl)-N' -ethyl-carbodiimide hydrochloride (EDOHC1), benzotriazol-l-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP), 2-chloro- 1,3-dimethylimidazolidinium hexafluorophosphate (CIP), l-hydroxy-7-azabenzotriazole (HOAt), or 0-benzotriazole-N,N,N',N'-tetramethyl-uronium-hexafluoro-phosphate (HBTU) in the presence of a base, such as N,N-diisopropylethylamine (DIPEA) or DMAP to give the molecules of Formula One, wherein Rl l is (C=0)N(R14)(R15), and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, XI , X2, and X3 are as previously disclosed.

Alternatively, the ester of Formula Xa is allowed to react with an amine (HN(R14)(R15)) in the presence of a solution of trimethylaluminum in toluene in a non-reactive solvent, such as CH2CI2, at ambient temperature, as in step o of Scheme VII, to access the molecules of

Formula One, wherein Rl l is (C=0)N(R14)(R15), and Rl , R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, XI , X2, and X3 are as previously disclosed.

Scheme VII

Formula One

In step I of Scheme VIII, the compound of Formula V, wherein Y, Rl , R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzoic acid ester of Formula VIIb2 or VIIb3, wherein Rl l is (C=0)0(C C₆ alkyl), and R8, R9, RIO, R12, R13, XI , X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180 °C to provide the compounds of Formula Xb, wherein Rl 1 is (C=0)OH, and Rl, R2, R3, R4, R5, R6, R7, R8, R9, RIO, R12, R13, R14, R15, XI, X2, and X3 are as previously disclosed. The compounds of Formula Xb are then converted to the molecules of Formula One, wherein Rl 1 is

(C=0)N(R14)(R15), and Rl, R2, R3, R4, R5, R6, R7, R8, R9, RIO, R12, R13, R14, R15, XI, X2, and X3 are as previously disclosed, in one step as disclosed in step n. In step n of Scheme VIII, the acid of Formula Xb can be coupled to an amine (HN(R14)(R15)), wherein R14 and R15 are as previously disclosed, using peptide coupling reagents, such as 1- hydroxybenzotriazole (HOBt), N-(3-dimethylaminopropyl)-N'-ethyl-carbodiimide hydrochloride (EDOHC1), benzotriazol- 1-yl-oxytripyrrolidinophosphonium

hexafluorophosphate (PyBOP), 2-chloro- l,3-dimethylimidazolidinium hexafluorophosphate (CIP), l-hydroxy-7-azabenzotriazole (HOAt), or 0-benzotriazole-N,N,N',N'-tetramethyl- uronium-hexafluoro-phosphate (HBTU) in the presence of a base, such as DIPEA or DMAP to give the molecules of Formula One, wherein Rl l is (C=0)N(R14)(R15), and Rl , R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, R14, R15, XI, X2, and X3 are as previously disclosed.

Scheme VIII

V VIIb2 or VIIb3

In step j of Scheme IX, the halobenzoketone of Formula VHIb, wherein R18 is Br, RIO and Rl l together form a linkage, having 3-4 carbon atoms and an oxo substituent and with the ring carbon atoms form a 5- or 6-membered cyclic ring, and R8, R9, R12, R13, XI, X2, and X3 are as previously disclosed, is allowed to react with vinyl boronic anhydride pyridine complex in the presence of a palladium catalyst, such as Pd(PPh₃)₄, and a base, such as K₂CO₃, in a non-reactive solvent such as toluene at reflux temperature, to provide the vinyl benzoketone of Formula VIIb4, wherein RIO and Rl 1 together form a linkage, having 3-4 carbon atoms and an oxo substituent and with the ring carbon atoms form a 5- or 6-membered ring, and R8, R9, R12, R13, XI, X2, and X3 are as previously disclosed.

Scheme IX

Vlllb VIIb4

In step I of Scheme X, the compound of Formula V, wherein Y, Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the vinylbenzoketone of Formula VIIb4 as previously disclosed, wherein R8, R9, R12, R13, XI, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2- dichlorobenzene, at a temperature of about 180 °C to provide the compounds of Formula Xc, wherein RIO and Rl 1 together form a linkage, having 3-4 carbon atoms and an oxo substituent and with the ring carbon atoms form a 5- or 6-membered ring, and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, XI, X2, and X3 are as previously disclosed. The compounds of Formula Xc are then converted to the molecules of Formula Xd, wherein RIO and Rl 1 together form a linkage, having 3-4 carbon atoms and an oxime [(C=N)(OH)] substituent and with the ring carbon atoms form a 5- or 6-membered ring,, and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, XI, X2, and X3 are as previously disclosed, in step p. In step p of Scheme X, the ketone of Formula Xc is allowed to react with hydroxylamine hydrochloride in the presence of sodium acetate and in a polar protic solvent, such as EtOH, at a temperature of about 78 °C, to give the molecules of Formula Xd as previously disclosed. Scheme X

The compounds of Formula Xc are also converted to the molecules of Formula Xe, wherein RIO and Rl l together form a linkage, having 3-4 carbon atoms and an amine substituent and with the ring carbon atoms form a 5- or 6-membered ring, and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, XI, X2, and X3 are as previously disclosed, as demonstrated in step q of Scheme XI. The ketone of Formula Xc is allowed to react with ammonium acetate in the presence of sodium cyanoborohydride and in a polar protic solvent, such as CH₃OH, at a temperature of about 65 °C, to give the molecules of Formula Xe.

heme XI

The compounds of Formula Xe are converted to the molecules of Formula One, wherein RIO and Rl l together form a linkage as previously disclosed in (u), and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, XI, X2, and X3 are as previously, in one step as disclosed in steps r or s. In step r of Scheme XII, the amine of Formula Xe is allowed to react with an isocyanate in a polar, aprotic solvent such as diethyl ether at ambient temperature to provide the molecules of Formula One as previously disclosed. In step s of Scheme XII, the amine of Formula Xe is coupled to an acid with HOBt'F^O and EDOHC1 in the presence of a base, such as DIPEA, in a non-reactive solvent, such as CH₂CI₂, to give the molecules of Formula One, as previously disclosed.

Scheme XII

Xe Formula One

In step t of Scheme XIII, the vinyl benzyl chloride of Formula XIa, wherein Rl 1 is - CH₂C1 and R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously defined, can be transformed into the corresponding phthalimide-protected benzyl amine of Formula Xlla, wherein Rl l is CH₂N(Phthalimide), and R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with potassium phthalimide in a polar aprotic solvent, such as DMF, at 70 °C.

Scheme XIII

XIa Xlla

In step u of Scheme XIV, the 4-methylbenzonitrile of Formula XHIa, wherein Rll is CH₃ and R9, RIO, R12, R13, XI, X2, and X3 are as previously defined, can be transformed into the corresponding benzyl bromide of Formula XlVa, wherein Rl 1 is CF^Br and R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with N- bromosuccinimide (NBS) and azobisisobutyronitrile (AIBN) in a non-reactive solvent, such as carbon tetrachloride at 77 °C. The nitrile group (CN) of Formula XlVa can be reduced to the corresponding aldehyde of Formula XVa, wherein Rl 1 is CF^Br and R9, RIO, R12, R13, XI, X2, and X3 are as previously defined via reaction with diisobutylaluminum hydride (DIBAL-H) in an aprotic solvent, such as toluene, at 0 °C, followed by quenching with 1.0 M hydrochloric acid (HC1) as in step v of Scheme XIV. The compound of Formula XVa can be further transformed to the corresponding phthalimide-protected benzyl amine of Formula XVIa, wherein Rl l is CH₂N(Phthalimide) and R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with potassium phthalimide in a polar aprotic solvent, such as DMF, at 60 °C as in step t of Scheme XIV. In step w of Scheme XIV, the aldehyde of Formula XVIa can be converted to the olefin of Formula Xllb, wherein Rl l is

CH₂N(Phthalimide) and R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with methyl triphenyl phosphonium bromide in a polar aprotic solvent, such as 1,4-dioxane, in the presence of a base, such as K₂CC>3, at ambient temperature.

Scheme XIV

XHIa XlVa XVa

XVIa Xllb

The aldehyde of Formula XVa, wherein Rl l is CH₂Br and R9, R10, R12, R13, XI, X2, and X3 are as previously defined, can be reacted with a nucleophile, such as 2- aminopyridine, in a polar aprotic solvent, such as N,N-dimethylacetamide (DMA), in the presence of a base, such as K₂CC>3, at ambient temperature to provide the compound of Formula XVII, wherein Rl l is CH₂NH(2-pyridine) and R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed, as in step x of Scheme XV. In step w of Scheme XV, the compound of Formula XVII can be converted to the olefin of Formula XVIII, wherein Rl l is CH₂NH(2-pyridine) and R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed.

Scheme XV

XVa XVII XVIII In a two-step, one-pot reaction as in steps y and z of Scheme XVI, the compound of Formula XIX can be reacted with the compounds of Formula XX, wherein RIO and Rl 1 are CI, XI is N, and R9, R13, X2, and X3 are as previously disclosed, in the presence of a base, such as sodium hydride (NaH), and a polar aprotic solvent, such as DMF, at ambient temperature to provide the compounds of Formula XXI, wherein RIO is CI, Rl 1 is

(CH)NH₂C0₂CH₂CH₃, XI is N, and R9, R13, X2, and X3 are as previously defined.

Hydrolysis and decarboxylation of the compounds of Formula XXI can be accomplished by reaction under acidic conditions, such as with 3 N HC1, at reflux temperature, to afford the compounds of Formula XXII, wherein RIO is CI, Rl 1 is CH₂NH₂ ^»HC1, XI is N, and R9, R13, X2, and X3 are as previously disclosed, as in step aa in Scheme XVI. The compounds of Formula XXII can be further transformed to the corresponding phthalimide-protected benzyl amines of Formula XXIIIa, wherein RIO is CI, Rl 1 is CH₂N(Phthalimide), XI is N, and R9, R13, XI, X2, and X3 are as previously disclosed, by reaction with phthalic anhydride in the presence of a base, such as TEA, and an aprotic solvent, such as toluene, at reflux temperature as in step ab of Scheme XVI. The bromide of Formula XXIIIa can be converted to the olefin of Formula XIIc, wherein RIO is CI, Rl 1 is CH₂N(Phthalimide), XI is N, and R8, R9, R13, X2 and X3 are as previously disclosed, by reaction with vinyl boronic anhydride pyridine complex in the presence of a palladium catalyst, such as Pd(PPh₃)₄, and a base, such as K₂CC>3, in a non-reactive solvent such as toluene at reflux temperature, as in step ac of Scheme XVI.

Scheme XVI

XIX XX XXI

XXII XXIIIa XIIc

In step u of Scheme XVII, the 4-methylnaphthonitrile of Formula XHIb, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, Rl l is CH₃, and R12, R13, XI and X2 are as previously defined, can be transformed into the corresponding naphthyl bromide of Formula XlVb, wherein X3 is CR9, RIO and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, Rl l is CH₂Br, and R12, R13, XI and X2 are as previously disclosed, by reaction with N-bromosuccinimide (NBS) and azobisisobutyronitrile (AIBN) in a non-reactive solvent, such as carbon tetrachloride at 77 °C. The nitrile group (CN) of Formula XlVb can be reduced to the corresponding aldehyde of Formula XVb, wherein X3 is CR9, RIO and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring (or if desired a non- aromatic ring), Rl l is CH₂Br, and R12, R13, XI and X2 are as previously defined via reaction with diisobutylaluminum hydride (DIBAL-H) in an aprotic solvent, such as toluene, at 0 °C, followed by quenching with 1.0 M HCl as in step v of Scheme XVII. The compound of Formula XVb can be further transformed to the corresponding phthalimide-protected benzyl amine of Formula XVIb, wherein X3 is CR9, RIO and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, Rl l is CH₂N(Phthalimide), and R12, R13, XI and X2 are as previously disclosed, by reaction with potassium phthalimide in a polar aprotic solvent, such as DMF, at 60 °C as in step t of Scheme XVII. In step w of Scheme XVII, the aldehyde of Formula XVIb can be converted to the olefin of Formula Xlld, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, Rl l is CH₂N(Phthalimide), and R8, R12, R13, XI and X2 are as previously disclosed, by reaction with methyl triphenyl phosphonium bromide in a polar aprotic solvent, such as 1,4-dioxane, in the presence of a base, such as K₂CC>3, at ambient temperature.

Scheme XVII

XHIb XlVb XVb

XVIb Xlld The compound of Formula XXIV, wherein Rl l is NHNH₂ ^»HC1 and R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, can be transformed into the corresponding phthalimide-protected hydrazine of Formula XXV, wherein Rl l is NHN(Phthalimide) and R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with phthalic anhydride in glacial acetic acid at reflux temperature as in step ad of Scheme XVIII. The bromide of Formula XXV can be converted to the olefin of Formula Xlle, wherein Rl 1 is NHN(Phthalimide) and R8, R9, RIO, R13, XI, X2 and X3 are as previously disclosed, by reaction with vinyl boronic anhydride pyridine complex in the presence of a palladium catalyst, such as Pd(PPh₃)₄, and a base, such as K₂CO₃, in a polar aprotic solvent such as 1,2- dimethoxyethane at 150 °C under microwave conditions, as in step ae of Scheme XVIII.

Scheme XVIII

XXIV XXV Xlle

In step af of Scheme ΧΓΧ, the compound of Formula XXVI, wherein Rl l is B(OH)₂, and R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed, are allowed to react with 2-hydroxyisoindoline-l,3-dione in the presence of CuCl and pyridine in a solvent, such as 1 ,2-dichlorobenzene, at ambient temperature to provide the compound of Formula Xllf , wherein Rl l is ON(Phthalimide) and R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed.

Scheme XIX

XXVI Xllf

In step I of Scheme XX, the compound of Formula V, wherein Y, Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula Xlla, wherein Rl 1 is CH₂N(Phthalimide) and R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1 ,2- dichlorobenzene, at a temperature of about 180 °C to provide the corresponding compounds of Formula XXVIIa, wherein Rl l is CH₂N(Phthalimide) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIa is removed as in step ag of Scheme XX by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90 °C to provide the compounds of Formula XXVIIIa, wherein Rl l is CH₂NH₂ and Rl, R2, R3, R4, R5, R6, R7, R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIa can be transformed into the compounds of Formula One, wherein Rl l is CH₂N(C=0)(R14) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, by acylation with an anhydride, such as acetic anhydride, and a base, such as TEA, in a non-reactive solvent such as CH₂C1₂ at 0 °C as in step ahi of Scheme XX.

XXVIIIa Formula One

In step I of Scheme XXI, the compound of Formula V, wherein Y, Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula Xllb, wherein Rl l is CH₂N(Phthalimide) and R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180 °C to provide the corresponding compounds of Formula XXVIIb, wherein Rl l is CH₂N(Phthalimide) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIb is removed as in step ag of Scheme XXI by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90 °C to provide the compounds of Formula XXVIIIb, wherein Rl 1 is CH₂NH₂ and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein Rl l is CH₂N(C=0)(R14) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with an acid in the presence of HOBt»H₂0, EDOHC1 and a base, such as DIPEA, in a polar aprotic solvent, such as DMF, as in step αίΐ2α of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein Rll is CH₂N(C=S)(R14) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with a thioacid in the presence of HOBt»H₂0, EDOHC1 and a base, such as DIPEA, in a polar aprotic solvent, such as DMF, as in step ah₂ of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein Rll is CH₂N(C=0)N(R14)(R15) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, in two steps. The first step (step ahs_a of Scheme XXI) involves reaction with an aldehyde in a polar protic solvent such as MeOH, followed by reaction with sodium borohydride. The second step (step ahy, of Scheme XXI) involves acylation with an acid chloride, such as

cyclopropylcarbonyl chloride, and a base, such as TEA, in a non-reactive solvent such as CH₂C1₂ at ambient temperature of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein Rll is CH₂N(C=0)N(R14)(R15) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with an isocyanate (step aii of Scheme XXI) or a carbamoyl chloride (step ai₂ of Scheme XXI) in the presence of a base such as TEA and in a non-reactive solvent such as CH₂C1₂ at 0 °C.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein Rll is CH₂N(C=S)N(R14)(R15) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with an isothiocyanate in the presence of a base such as TEA and in a non-reactive solvent such as CH₂C1₂ at 0 °C, as in steps aj of Scheme XXI.

In another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein Rll is CH₂N(C=0)0(R14) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with a dicarbonate, such as di-ieri-butyl dicarbonate in the presence of a base such as TEA and in a non-reactive solvent such as CH₂C1₂ at ambient temperature, as in steps ak of

Scheme XXI. In yet another embodiment, the compounds of Formula XXVIIIb can be transformed into the compounds of Formula One, wherein Rl l is CH₂N(C=0)(C=0)0(R14) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with a chlorooxalic acid ester, such as 2-chloro-2-oxoacetate in the presence of a base such as TEA and in a non-reactive solvent such as CH₂C1₂ at 0 °C, as in steps al of Scheme XXI.

In step I of Scheme XXII, the compound of Formula V, wherein Y, Rl, R2, R3, R4,

R5, R6, and R7 are as previously disclosed, and the compounds of Formula XIIc, wherein RIO is CI, Rl 1 is CH₂N(Phthalimide), XI is N, and R8, R9, R12, R13, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1 ,2-dichlorobenzene, at a temperature of about 180 °C to provide the corresponding compounds of Formula XXVIIc, wherein R10 is CI, Rl 1 is

CH₂N(Phthalimide), XI is N, and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIc is removed as in step ag of Scheme XXII by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90 °C to provide the compounds of Formula XXVIIIc, wherein R10 is CI, Rl l is CH₂NH₂, XI is N, and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIc can be transformed into the compounds of Formula One, wherein R10 is CI, Rl 1 is

CH₂N(C=0)(R14), XI is N, and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, X2, and X3 are as previously disclosed, by reaction with an acid in the presence of HOBt^»H₂0, EDC^»HC1 and a base, such as DIPEA, in a polar aprotic solvent, such as CH2CI2, as in step ali2b of Scheme XXII.

XXVIIIc Formula One

In step I of Scheme XXIII, the compound of Formula V, wherein Y, Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula Xlld, wherein X3 is CR9, RIO and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring (or if desired a non-aromatic ring), Rll is

CH₂N(Phthalimide) and R8, R9, R12, R13, XI and X2 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1 ,2- dichlorobenzene, at a temperature of about 180 °C to provide the corresponding compounds of Formula XXVIId, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, Rl 1 is CH₂N(Phthalimide) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, XI and X2 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIId is removed as in step ag of Scheme XXIII by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90 °C to provide the compounds of Formula XXVIIId, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, Rl l is CH₂NH₂ and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, XI and X2 are as previously disclosed. The compounds of Formula XXVIIId can be transformed into the compounds of Formula One, wherein X3 is CR9, R10 and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, Rl l is CH₂N(C=0)(R14) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, XI and X2 are as previously disclosed, by reaction with an acid in the presence of HOBt^»H₂0, EDOHC1 and a base, such as DIPEA, in a polar aprotic solvent, such as CH2CI2, as in step ati_2b of Scheme XXIII.

In another embodiment, the compounds of Formula XXVIIId can be transformed into the compounds of Formula One, wherein X3 is CR9, RIO and X3 together form a linkage having 4 carbon atoms and with the ring carbon atoms form a 6-membered aromatic ring, Rl l is CH₂N(C=0)N(R14)(R15) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, RIO, R12, R13, XI and X2 are as previously disclosed, by reaction with an isocyanate in the presence of a base such as TEA and in a non-reactive solvent such as CH₂C1₂ at 0 °C as in step aii of Scheme XXIII.

Scheme ΧΧΠΙ

Xlld XXVIId

XXVIIId Formula One

In step I of Scheme XXIV, the compound of Formula V, wherein Y, Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula Xlle, wherein Rl l is NHN(Phthalimide) and R8, R9, R12, R13, XI, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180 °C to provide the corresponding compounds of Formula XXVIIe, wherein Rl l is NHN(Phthalimide) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, XI, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIe is removed as in step ag of Scheme XXIV by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90 °C to provide the compounds of Formula XXVIIIe, wherein Rl l is NHNH₂ and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, XI, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIe can be transformed into the compounds of Formula One, wherein Rl 1 is NHN(C=0)(R14) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with an acid in the presence of HOBt»H₂0, EDOHC1 and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂C1₂, as in step ati2b of Scheme XXIV.

XXVIIIe Formula One

In step I of Scheme XXV, the compound of Formula V, wherein Y, Rl, R2, R3, R4,

R5, R6, and R7 are as previously disclosed, and the compounds of Formula Xllf, wherein Rll is ON(Phthalimide) and R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180 °C to provide the corresponding compounds of Formula XXVIIf, wherein Rll is ON(Phthalimide) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed. The phthalimide protecting group in the compounds of Formula XXVIIf is removed as in step ag of Scheme XXV by reaction with hydrazine hydrate in a polar protic solvent such as EtOH at 90 °C to provide the compounds of Formula XXVIIIf, wherein Rll is ONH₂ and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed. The compounds of Formula XXVIIIf can be transformed into the compounds of Formula One, wherein Rl 1 is ON(C=0)(R14) and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, R12, R13, XI, X2, and X3 are as previously disclosed, by reaction with an acid in the presence of HOBt»H₂0, EDOHC1 and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂C1₂, as in step ati2b of Scheme XXV.

XXVIIIf Formula One

In step I of Scheme XXVI, the compound of Formula V, wherein Y, Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XVIII, wherein Rll is CH₂NH(2-pyridine) and R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180 °C to provide the corresponding compounds of Formula One, wherein Rll is CH₂NH(2-pyridine), and Rl, R2, R3, R4, R5, R6, R7, R8, R9, RIO, R12, R13, XI, X2, and X3 are as previously disclosed.

The compounds of Formula One can be further elaborated by standard methods. For example, when Rl 1 contains a thioether, the thioether can be oxidized to the sulfone by treatment with oxone in the presence of an acetone:water mixture at ambient temperature. When Rll contains an oxalate ester, the compound of Formula One can be transformed into the corresponding oxalamide by reaction with an amine hydrochloride and a solution of trimethylaluminum in toluene in a non-reactive solvent such as CH₂C1₂.

V XVIII Formula One

In Scheme XXVII, a fluorobenzaldehyde of Formula ΧΧΓΧ, wherein R10, XI, X2, are as previously disclosed can be converted to a (l,2,4-triazol-l-yl)benzaldehyde ( Formula XXX, wherein Rll is a substituted or unsubstituted 1,2,4-triazol-l-yl group, and RIO, XI, X2, and X3 are as previously disclosed by reaction with a substituted or unsubstituted 1,2,4-triazole in the presence of a base, such as potassium carbonate, in a solvent such as DMF as in step aj. In step ak, the (l,2,4-triazol-l-yl)benzaldehyde of Formula XXX is converted to a (l,2,4-triazol-l-yl)vinyl benzene of Formula XXXIa wherein Rl 1 is a substituted or unsubstituted 1,2,4-triazol-l-yl group, and R8, RIO, XI, X2, and X3 are as previously disclosed by reaction with triphenyl phosphonium bromide in the presence of a base, such as potassium carbonate, in an aprotic solvent, such as 1,4-dioxane.

Scheme XXVII

XXIX XXX XXXIa

In Scheme XXVIII, a bromofluorobenzene of Formula XXXII, wherein RIO, XI, X2, and X3 are as previously disclosed can be converted to a (l,2,4-triazol-l-yl)vinylbenzene of Formula XXXIb, wherein Rll is a substituted or unsubstituted 1,2,4-triazol-l-yl group, and R8, RIO, XI, X2, and X3 are as previously disclosed in two steps. In step al, the

bromofluorobenzene is reacted with a substituted or unsubstituted 1,2,4-triazole in the presence of a base, such as potassium carbonate, in a solvent such as DMF to generate the (l,2,4-triazol-l-yl)bromobenzene. In step cl, the (l,2,4-triazol-l-yl)bromobenzene is reacted with vinyl boronic anhydride pyridine complex in the presence of a catalyst, such as Pd (PPh₃)₄, and a base, such as potassium carbonate in a solvent such as toluene.

Scheme XXVIII

Coupling of the compounds of Formula V with compounds of Formula XXXIa and XXXIb can be accomplished as in Schemes ΧΧΓΧ. In step I, a compound of Formula V, wherein Y is Br, Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and a vinylbenzene of Formula XXXIa or XXXIb, wherein Rl 1 is a substituted or unsubstituted 1,2,4-triazol-l-yl group, and R8, R9, RIO, XI, X2, and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1 ,2- dichlorobenzene, at a temperature of about 180 °C to provide the molecules of Formula One, wherein Rl l is a substituted or unsubstituted 1,2,4-triazol-l-yl group, and Rl, R2, R3, R4, R5, R6, R7, R8, RIO, XI, X2, and X3 are as previously disclosed.

Scheme XXIX

XXXIa or XXXIb Formula One In Scheme XXX, compounds of Formula XXXIII wherein Rl 1 is a 3-nitro- 1,2,4- triazol-l-yl group, and Rl, R2, R3, R4, R5, R6, R7, R8, R10, XI, X2, and X3 are as previously disclosed can be converted to compounds of Formula One, wherein Rl 1 is a 3- amido- 1,2,4-triazol-l-yl group, and Rl, R2, R3, R4, R5, R6, R7, R8, R10, XI, X2, and X3 are as previously disclosed by a two-step process. In step am, the 3-nitro-l,2,4-triazol-l-yl group is reduced to a 3-amino-l,2,4-triazol-l-yl group in the presence of zinc dust and ammonium chloride in a protic solvent, such as MeOH. In step an, the 3 -amino- 1,2,4-triazol- l-yl group is acylated with an acid chloride, such as cyclopropylcarbonyl chloride or acetyl chloride, in the presence of a base, such as TEA, in a solvent such as CH₂CI₂.

Scheme XXX

XXXIII Formula One

In step ao of Scheme XXXI, a bromophenyl methyl ketone of Formula XXXIV wherein R10, XI, X2, and X3 are as previously disclosed is converted to an phenyl methyl ketone of the Formula XXXV wherein Rll is a 1,2,4-triazol-l-yl group, and RIO, XI, X2, and X3 are as previously disclosed by treatment with 1,2,4-triazole in the presence of a base, such as cesium carbonate, and a catalyst, such as copper iodide, in a solvent, such as DMF. In step ap, the 1,2,4-triazolylacetophenone of Formula XXXV is converted to the trimethylsilyl enol ether of Formula XXXVI by treatment with trimethylsilyl triflluoromethanesulfonate in the presence of a base, such as TEA, in an aprotic solvent, such as CH₂CI₂. In step aq, the silyl enol ether is reacted with a compound of Formula V, wherein Y is Br, Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene at a temperature of about 180 °C to generate a ketone of the Formula XXXVII, wherein Rl 1 is a 1,2,4-triazol-l-yl group, and Rl, R2, R3, R4, R5, R6, R7, R10, XI, X2, and X3 are as previously disclosed. In step ar, the ketone of the Formula XXXVII is treated with methylmagnesium bromide in an aprotic solvent, such as THF to generate the tertiary alcohol. The tertiary alcohol then undergoes an elimination reaction when treated with a catalytic amount of p-toluenesulfonic acid in a solvent, such as toluene, when heated to a temperature to allow azeotropic removal of water to produce compounds of Formula One wherein Rll is a 1,2,4-triazol-l-yl group, R8 is methyl, and Rl, R2, R3, R4,

R5, R6, R7, RIO, XI, X2, and X3 are as previously disclosed, as in step as.

Scheme XXXT

XXXIV XXXV XXXVI

Formula One

In Scheme XXXII, a compound of Formula XXXVIII, wherein RIO and Rl l together form a linkage, having 3-4 carbon atoms and an oxo substituent and with the ring carbon atoms form a 5- or 6-membered cyclic ring, and Rl, R2, R3, R4, R5, R6, R7, R8, XI, X2, and X3 are as previously disclosed is converted to a molecule of Formula One, wherein RIO and Rl l together form a linkage, having 3-4 carbon atoms and an alkylamine substituent with the ring carbon atoms form a 5- or 6-membered cyclic ring and Rl, R2, R3, R4, R5, R6, R7, R8, XI, X2, and X3 are as previously disclosed, by treatment with an alkylamine, such as 3,3,3-trifluoropropylamine, in the presence of a reducing agent, such as sodium

cyanoborohydride, in a solvent, such as DCE. Scheme XXXII

XXXVIII Formula One

In Scheme XXXIII, a compound of Formula ΧΧΧΓΧ, wherein XI, X2, and X3 are as previously disclosed is converted to a molecule of Formula XL, wherein XI, X2, and X3 are as previously disclosed, by treatment with a reducing agent, such as sodium

cyanoborohydride, in a solvent, such as acetic acid, as in step au. In step av, the nitrogen atom is protected with a ieri-butyloxycarbonyl (BOC) group by reaction with di-ieri-butyl dicarbonate in the presence of a catalyst, such as DMAP, in a solvent, such as acetonitrile. The bromide of Formula XL can be converted to the olefin of Formula XLI, wherein R8, XI, X2 and X3 are as previously disclosed, by reaction with potassium vinyl trifluoroborate in the presence of a palladium catalyst, such as PdCl₂(dppf), and a base, such as K₂CO₃, in a polar aprotic solvent such as DMSO at 100 °C, as in step aw.

Scheme XXXIII

In Scheme XXXIV, a compound of Formula XXXIX, wherein XI, X2, and X3 are as previously disclosed is converted to a molecule of Formula XLII, wherein XI, X2, and X3 are as previously disclosed in two steps. In step ax, the olefin is formed by treatment of the bromide with potassium vinyl trifluoroborate in the presence of a palladium catalyst, such as PdCl₂, and a ligand, such as triphenylphosphine, and a base, such as CS₂CO₃, in a solvent mixture such as THF/water. In step ay, the nitrogen atom is protected with a tert- butyloxycarbonyl (BOC) group by reaction with di-ieri-butyl dicarbonate in the presence of a catalyst, such as DMAP, in a solvent, such as acetonitrile. Scheme XXXIV

XXXIX XLII

In step I of Scheme XXXV, the compound of Formula V, wherein Y, Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compounds of Formula XLI or XLII, wherein R8, XI, X2 and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 150 °C to provide the corresponding compounds of Formula XLIIIa or XLIIIb, wherein Rl, R2, R3, R4, R5, R6, R7, R8, XI, X2, and X3 are as previously disclosed.

Scheme XXXV

V XLI or XLII XLIIIa or XLIIIb In Scheme XXXVI, a compound of Formula XLIIIa, wherein Rl, R2, R3, R4, R5, R6,

R7, R8, XI, X2, and X3 are as previously disclosed is converted to a molecule of Formula XLIV, wherein Rl, R2, R3, R4, R5, R6, R7, R8, XI, X2, and X3 are as previously disclosed by treatment with trifluoroacetic acid, in a solvent such as CH₂CI₂, as in step az. Compounds of the Formula XLIV can then be transformed into compounds of the Formula XLV wherein Rl, R2, R3, R4, R5, R6, R7, R8, XI, X2, and X3 are as previously disclosed, in two steps. In step ba, the indoline is treated with sodium nitrite (NaN0₂), in an acid, such as concentrated HC1, at a temperature around 5 °C, to form the nitrosoindole. In step bb, the nitrosoindole is reacted with ammonium chloride in the presence of zinc powder in a protic solvent, such as MeOH. In step be, compounds of the Formula XLV are transformed into compounds of the Formula XLVI, wherein X4 is N(R14)(C(=0)R14) and Rl, R2, R3, R4, R5, R6, R7, R8, XI, X2, and X3 are as previously disclosed, by treatment with and acid, such as 3,3,3- trifluoropropanoic acid, PyBOP, and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂C1₂.

Scheme XXXVI

In Scheme XXXVII, a compound of Formula XLIIIb, wherein Rl, R2, R3, R4, R5, R6, R7, R8, XI, X2, and X3 are as previously disclosed is converted to an indole of Formula XLVII, wherein Rl, R2, R3, R4, R5, R6, R7, R8, XI, X2, and X3 are as previously disclosed by treatment with trifluoroacetic acid, in a solvent such as CH₂CI₂, as in step bd. Compounds of the Formula XLVII can be transformed into compounds of the Formula XLVIII wherein Rl, R2, R3, R4, R5, R6, R7, R8, XI, X2, and X3 are as previously disclosed, by reaction with 4-nitrophenyl-2-((ieri-butoxycarbonyl)amino)acetate in the presence of potassium fluoride and a crown ether, such as 18-crown-6-ether, in a solvent, such as acetonitrile, as in step be. Compounds of the Formula XLVIII can be transformed into compounds of the Formula XLIX, wherein Rl, R2, R3, R4, R5, R6, R7, R8, XI, X2, and X3 are as previously disclosed in two steps. In step bf, the Boc group is removed by treatment with trifluoroacetic acid, in a solvent such as CH₂CI₂. In step bg, the amine is treated with 3,3,3- trifluoropropanoic acid, PyBOP, and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂C1₂. Scheme XXXVII

In Scheme XXXVIII, a compound of Formula L, wherein XI, X2, and X3 are as previously disclosed is converted to a compound of the Formula LI, wherein XI, X2, and X3 are as previously disclosed by treatment with copper (II) sulfate pentahydrate and Zn powder in a base, such as sodium hydroxide as in step bh. Compounds of the Formula LI can be transformed into compounds of the Formula LII wherein XI, X2, and X3 are as previously disclosed, by reaction with hydrazine, in a solvent such as water, at a temperature around 95 °C, as in step bi. In step bj, the olefin of the Formula LIII wherein XI, X2, and X3 are as previously disclosed is formed by treatment of the bromide with potassium vinyl

trifluoroborate in the presence of a palladium catalyst, such as PdCl2(dppf), and a base, such as K2CO₃, in a solvent mixture such as DMSO. Compounds of the Formula LIV, wherein XI, X2, and X3 are as previously disclosed, can be formed from compounds of the Formula LIII by reaction with ethyl bromoacetate, in the presence of a base, such as CS2CO₃, in a solvent, such as DMF.

Scheme XXXVIII

In step I of Scheme XXXIX, the compound of Formula V, wherein Y, Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed, and the compound of Formula LIV, wherein R8, XI, X2 and X3 are as previously disclosed, are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as 1,2-dichlorobenzene, at a temperature of about 180 °C to provide the corresponding compound of Formula LV, wherein Rl, R2, R3, R4, R5, R6, R7, R8, XI, X2, and X3 are as previously disclosed. The compound of Formula LV can be further transformed into a compound of the Formula LVI, wherein Rl, R2, R3, R4, R5, R6, R7, R8, XI, X2, and X3 are as previously disclosed, in two steps. In step bl, the ester is hydrolyzed to the acid in the presence of HC1 and acetic acid, at a temperature of about 100 °C. In step bm, the acid is treated with an amine, such as 2,2,2-trifluoroethylamine, PyBOP, and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂C1₂.

Scheme XXXIX

LV

LVI

In step bn of Scheme XL, carboxylic acids of the Formula LVII, wherein Rl 1 is C(=0)OH and R8, RIO, XI, X2, and X3 are as previously disclosed and compounds of the Formula V, wherein Y is Br and Rl, R2, R3, R4, R5, R6, and R7 are as previously disclosed are allowed to react in the presence of CuCl and 2,2-bipyridyl in a solvent, such as N-methyl pyrrolidine, at a temperature of about 150 °C to afford compounds of Formula LVIII, wherein Rl l is (C=0)OH and Rl, R2, R3, R4, R5, R6, R7, R8, R9, RIO, XI, X2, and X3 are as previously disclosed. Compounds of the Formula LVIII can be further transformed to the corresponding benzamides of Formula LIX, wherein Rl l is (C=0)N(R14)(R15), and Rl, R2, R3, R4, R5, R6, R7, R8, R9, R10, XI, X2, and X3 are as previously disclosed, by treatment with an amine, such as 2-amino-N-(2,2,2-trifluoroethyl)acetamide, PyBOP, and a base, such as DIPEA, in a polar aprotic solvent, such as CH₂CI₂, as in step bo. Scheme XL

LIX

EXAMPLES

The examples are for illustration purposes and are not to be construed as limiting the invention disclosed in this document to only the embodiments disclosed in these examples.

Starting materials, reagents, and solvents that were obtained from commercial sources were used without further purification. Anhydrous solvents were purchased as Sure/Seal™ from Aldrich and were used as received. Melting points were obtained on a Thomas Hoover Unimelt capillary melting point apparatus or an OptiMelt Automated Melting Point System from Stanford Research Systems and are uncorrected. Molecules are given their known names, named according to naming programs within ISIS Draw, ChemDraw, or ACD Name Pro. If such programs are unable to name a molecule, the molecule is named using conventional naming rules. ^]H NMR spectral data are in ppm (δ) and were recorded at 300, 400, or 600 MHz, and ¹³C NMR spectral data are in ppm (δ) and were recorded at 75, 100, or 150 MHz, unless otherwise stated.

Example 1: Preparation of l-(l-Bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (All)

Step 1 Method A. l-(3,5-Dichlorophenyl)-2,2,2-trifluoroethanol (AI2). To a stirred solution of l-(3,5-dichlorophenyl)-2,2,2-trifluoroethanone (procured from Rieke Metals, UK; 5.0 grams (g), 20.5 millimoles (mmol)) in MeOH (100 mL) at 0 °C were added sodium borohydride (NaBH₄; 3.33 g, 92.5 mL) and 1 Normal (N) aqueous sodium hydroxide solution (NaOH; 10 mL). The reaction mixture was warmed to 25 °C and stirred for 2 hours (h). After the reaction was deemed complete by thin layer chromatography (TLC), saturated (satd) aqueous (aq) ammonium chloride (NH₄C1) solution was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The residue was diluted with diethyl ether (Et₂0) and washed with water (3 x 50 mL). The organic layer was dried over sodium sulfate (Na₂S0₄) and concentrated under reduced pressure to afford the title compound as a liquid (4.0 g, 79%): ^]H NMR (400 MHz, CDC1₃) δ 7.41 (m, 3H), 5.00 (m, 2H), 2.74 (s, 1H); ESIMS m/z 242.97 ([M-H]^").

Step 1 Method B. l-(3,5-Dichlorophenyl)-2,2,2-trifluoroethanol (AI2). To a stirred solution of 3,5-dichlorobenzaldehyde (10 g, 57 mmol) in THF (250 mL) were added trifluoromethyltrimethylsilane (9.79 g, 69.2 mmol) and a catalytic amount of

tetrabutylammonium fluoride (TBAF). The reaction mixture was stirred at 25 °C for 8 h. After the reaction was deemed complete by TLC, the reaction mixture was diluted with 3 N hydrochloric acid (HCl) and then was stirred for 16 h. The reaction mixture was diluted with water and was extracted with ethyl acetate (EtOAc; 3 x). The combined organic extracts were washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure to afford the title compound as a liquid (8.41 g, 60%).

The following compounds were made in accordance with the procedures disclosed in Step 1 Method B of Example 1 above.

2,2,2-Trifluoro-l-(3,4,5-trichlorophenyl)ethanol (AI3)

The product was isolated as a pale yellow liquid (500 mg, 65%): ^]H NMR (400 MHz, CDCI₃) δ 7.45 (s, 2H), 5.00 (m, 1H), 2.80 (s, 1H); ESIMS m/z 278 ([M+H]⁺); IR (thin film) 3420, 1133, 718 cm^"1.

l-(3,5-Dichloro-4-fluorophenyl)-2,2,2-trifluoroethanol (AI4)

The product was isolated as a pale yellow liquid (500 mg, 65%): ^]H NMR (400 MHz, CDC1₃) δ 7.41 (s, 2H), 5.00 (m, IH), 2.80 (s, IH); ESIMS m/z 262 ([M+H]⁺); IR (thin film) 3420, 1133, 718 cm^"1.

l-(3,4-Dichlorophenyl)-2,2,2-trifluoroethanol (AI5)

The product was isolated as a pale yellow liquid (500 mg, 65%): ^]H NMR (400 MHz, CDCI₃) δ 7.60 (s, IH), 7.51 (m, IH), 7.35 (m, IH), 5.01 (m, IH), 2.60 (s, IH); EIMS m/z 244 «M]⁺).

Step 2. l-(l-Bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (All). To a stirred solution of l-(3,5-dichlorophenyl)-2,2,2-trifluoroethanol (4.0 g, 16.3 mmol) in CH₂C1₂ (50 mL), were added N-bromosuccinimide (NBS; 2.9 g, 16.3 mmol) and triphenyl phosphite (5.06 g, 16.3 mmol), and the resultant reaction mixture was heated at reflux for 18 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to 25 °C and was concentrated under reduced pressure. Purification by flash column chromatography (Si0₂, 100-200 mesh; eluting with 100% pentane) afforded the title compound as a liquid (2.0 g, 40%): ^]H NMR (400 MHz, CDC1₃) δ 7.41 (s, 3H), 5.00 (m, IH); EIMS m/z 306 ([M]⁺).

The following compounds were made in accordance with the procedures disclosed in Step 2 of Example 1.

5-(l-Bromo-2,2,2-trifluoroethyl)-l,2,3-trichlorobenzene (AI6)

The product was isolated as a colorless oil (300 mg, 60%): ^]H NMR (400 MHz, CDCI₃) δ 7.59 (s, 2H), 5.00 (m, IH); EIMS m/z 340.00 ([M]⁺).

5-(l-Bromo-2,2,2-trifluoroethyl)-l,3-dichloro-2-fluorobenzene (AI7)

The product was isolated as a colorless oil (320 mg, 60%)

CDC1₃) δ 7.45 (s, 2H), 5.00 (m, 2H); EIMS m/z 324.00 ([M]⁺).

4-(l-Bromo-2,2,2-trifluoroethyl)-l,2-dichlorobenzene (AI8)

The product was isolated as a colorless oil (300 mg, 60%): ^]H NMR (400 MHz, CDCI₃) δ 7.63 (s, 1H), 7.51 (m, 1H), 7.35 (m, 1H), 5.01 (m, 1H); EIMS m/z 306.00 ([M]⁺). Example 2: Preparation of jV-Meth -4-vinylbenzamide (AI9)

Step 1. 4-Vinylbenzoyl chloride (AI10). To a stirred solution of 4-vinylbenzoic acid (1 g, 6.75 mmol) in CH₂C1₂ (20 mL) at 0 °C were added a catalytic amount of N,N- dimethylformamide (DMF) and oxalyl chloride (1.27 g, 10.12 mmol) dropwise over a period of 15 minutes (min). The reaction mixture was stirred at 25 °C for 6 h. After the reaction was deemed complete by TLC, the reaction mixture was concentrated under reduced pressure to give the crude acid chloride.

Step 2. V-Methyl-4-vinylbenzamide (AI9). To 1 M N-methylamine in THF (13.5 mL, 13.5 mmol) at 0 °C were added TEA (1.34 mL, 10.12 mmol) and the acid chloride from Step 1 above in THF (10 mL), and the reaction mixture was stirred at 25 °C for 3 h. After the reaction was deemed complete by TLC, the reaction mixture was quenched with water and then was extracted with EtOAc (3x). The combined EtOAc layer was washed with brine and dried over Na₂S0₄ and concentrated under reduced pressure to afford the title compound as an off-white solid (650 mg, 60%): ^]H NMR (400 MHz, CDC1₃) δ 7.76 (d, J = 8.0 Hz, 2H), 7.45 ( d, J = 8.0 Hz, 2H), 6.79 (m, 1H), 6.20 (br s, 1H), 5.82 (d, J = 17.6 Hz, 1H), 5.39 (d, J = 10.8 Hz, 1H); ESIMS m/z 161.95 ([M+H]⁺).

The following compounds were made in accordance with the procedures disclosed in accordance with Example 2.

jV,jV-Dimethyl-4-vinylbenzamide (AI11)

The product was isolated as an off-white solid (650 mg, 60%): ^]H NMR (400 MHz, CDC1₃) δ 7.42 (m, 4H), 6.71 (m, IH), 5.80 (d, / = 17.6 Hz, IH), 5.31 (d, / = 10.8 Hz, IH), 3.05 (s, 3H), 3.00 (s, 3H); ESIMS m/z 176.01 ([M+H]⁺).

V-(2,2,3-Trifluoromethyl)-4-vinylbenzamide (AI12)

The product was isolated as an off-white solid (900 mg, 60%): ^]H NMR (400 MHz, CDCI₃) δ 7.76 (d, J = 8.0 Hz, 2H), 7.45 ( d, / = 8.0 Hz, 2H), 6.79 (m, IH), 6.20 (br s, IH), 5.82 (d, J = 17.6 Hz, IH), 5.39 (d, J = 10.8 Hz, IH), 4.19 (m, 2H); ESIMS m/z 230.06 «M+H]⁺).

M orpholino(4- vinylphenyl)methanone (AI 13)

The product was isolated as a white solid (850 mg, 60%): ESIMS m/z 218.12 «M+H]⁺).

Example 3: Preparation of Ethyl -methyl-4-vinylbenzoate (AI14)

Step 1. 4-Formyl-2-methylbenzoic acid (AI15). To a stirred solution of 4-bromo-2- methylbenzoic acid (10 g, 46.4 mmol) in dry THF (360 mL) at -78 °C was added n-BuLi (1.6 M solution in hexane; 58.17 mL, 93.0 mmol) and DMF (8 mL). The reaction mixture was stirred at -78 °C for 1 h then was warmed to 25 °C and stirred for 1 h. The reaction mixture was quenched with 1 N HC1 solution and extracted with EtOAc. The combined EtOAc extracts were washed with brine and dried over Na₂SC>₄ and concentrated under reduced pressure. The residue was washed with n-hexane to afford the title compound as a solid (3.0 g, 40%): mp 196-198 °C; ^]H NMR (400 MHz, DMSO-d₆) δ 13.32 (br s, IH), 10.05 (s, IH), 7.98 (m, IH), 7.84 (m, 2H), 2.61 (s, 3H); ESIMS m/z 163.00 ([M-H]^"). Step 2. Ethyl 4-formyl-2-methylbenzoate (AI16). To a stirred solution of 4-formyl- 2-methylbenzoic acid (3 g, 18.2 mmol) in ethyl alcohol (EtOH; 30 mL) was added sulfuric acid (H₂SO₄, x M; 2 mL), and the reaction mixture was heated at 80 °C for 18 h. The reaction mixture was cooled to 25 °C and concentrated under reduced pressure. The residue was diluted with EtOAc and washed with water. The combined EtOAc extracts were washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure to afford the title compound as a solid (2.8 g, 80%): ^]H NMR (400 MHz, CDC1₃) δ 10.05 (s, 1H), 8.04 (m, 1H), 7.75 (m, 2H), 4.43 (m, 2H), 2.65 (s, 3H), 1.42 (m, 3H).

Step 3. Ethyl 2-methyl-4-vinylbenzoate (AI14). To a stirred solution of ethyl 4- formyl-2-methylbenzoate (2.8 g, 4 mmol) in 1,4-dioxane (20 mL) were added potassium carbonate (K2CO₃; 3.01 g, 21.87 mmol) and methyltriphenyl phosphonium bromide (7.8 g, 21.87 mmol) at 25 °C. Then the reaction mixture was heated at 100 °C for 18 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to 25 °C and filtered, and the filtrate was concentrated under reduced pressure. The crude compound was purified by flash chromatography (S1O₂, 100-200 mesh; eluting with 25-30% EtOAc in n- Hexane) to afford the title compound as a solid (2.0 g, 72%): ^]H NMR (400 MHz, CDC1₃) δ 7.86 (m, 1H), 7.27 (m, 2H), 6.68 (dd, J =17.6, 10.8 Hz , 1H), 5.84 (d, J = 17.6 Hz, 1H), 5.39 (d, / = 10.8 Hz, 1H), 4.39 (m, 2H), 2.60 (s, 3H), 1.40 (m, 3H); ESIMS m/z 191.10 ([M-H]^"); IR (thin film) 2980, 1716, 1257 cm^"1.

Example 4: Preparation of tert-Bu l 2-chloro-4-vinylbenzoate (AI17)

Step 1. fert-Butyl 4-bromo-2-chlorobenzoate (AI18). To a stirred solution of 4- bromo-2-chlorobenzoic acid (5 g, 21.37 mmol) in THF (30 mL) was added di-ieri-butyl dicarbonate (25.5 g, 25.58 mmol), TEA (3.2 g, 31.98 mmol) and DMAP (0.78 g, 6.398 mmol), and the reaction mixture was stirred at 25 °C for 18 h. The reaction mixture was diluted with EtOAc and washed with water. The combined organic layer was washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure. The residue was purified by flash chromatography (S1O₂, 100-200 mesh; eluting with 2-3% EtOAc in n-hexane) to afford the title compound as a liquid (3.2 g, 51%): ^]H NMR (400 MHz, CDC1₃) δ 7.62 (m, 2H), 7.44 (d, J = 8.4 Hz, 1H), 1.59 (s, 9H); ESIMS m/z 290.10 ([M+H]⁺); IR(thin film) 1728 cm -1 The following compounds were made in accordance with the procedures disclosed in Step 1 of Example 4.

tert-Butyl 2-bromo-4-iodobenzoate

The product was isolated as a colorless oil (1.2 g, 50%): ^]H NMR (400 MHz, CDC1₃) δ 8.01 (s, 1H), 7.68 (d, / = 8.4 Hz, 1H), 7.41 (d, / = 8.0 Hz, 1H), 1.59 (s, 9H); ESIMS m/z 382.10 ([M+H]⁺); IR(thin film) 1727 cm^"1.

tert-Butyl 4-bromo-2-(trifluoromethyl)benzoate(AI20)

The product was isolated as a colorless oil (1 g, 52%): ^]H NMR (400 MHz, CDC1₃) δ 7.85 (s, 1H), 7.73 (d, / = 8.4 Hz, 1H), 7.62 (d, / = 8.4 Hz, 1H), 1.57 (s, 9H); ESIMS m/z 324.10 ([M+H]⁺); IR (thin film) 1725 cm^"1.

Step 2. tert-Butyl 2-chloro-4-vinylbenzoate (AI17). To a stirred solution of tert- butyl 4-bromo-2-chlorobenzoate (1.6 g, 5.50 mmol) in toluene (20 mL) was added tetrakis(triphenylphospine)palladium(0) (Pd(PPh₃)₄; (0.31 mg, 0.27 mmol), K₂C0₃ (2.27 g, 16.5 mmol) and vinylboronic anhydride pyridine complex (2.0 g, 8.3 mmol) and the reaction mixture was heated to reflux for 16 h. The reaction mixture was filtered, and the filtrate was washed with water and brine, dried over Na₂S0₄ and concentrated under reduced pressure. Purification by flash column chromatography (Si0₂, 100-200 mesh; eluting with 5-6% EtOAc in n-hexane) afforded the title compound as a liquid (0.6 g, 46%): ^]H NMR (400 MHz, CDCI₃) δ 7.72 (d, 7 = 8.1 Hz, 1H), 7.44 (m, 1H), 7.31 ( d, / = 8.0 Hz, 1H), 6.69 (dd, J =17.6, 10.8 Hz , 1H) , 5.85 (d, J = 17.6 Hz, 1H), 5.40 (d, J = 10.8 Hz, 1H), 1.60 (s, 9H); ESIMS m/z 238.95 ([M+H]⁺); IR (thin film) 2931, 1725, 1134 cm^"1.

The following compounds were made in accordance with the procedures disclosed in Step 2 of Example 4.

tert-Butyl 2-bromo-4-vinylbenzoat The product was isolated as a colorless oil (lg, 52%): ^]H NMR (400 MHz, CDC1₃) δ 7.68 (m, 2H), 7.36 ( d, / = 8.0 Hz, 1H), 6.68 (dd, J =17.6, 10.8 Hz , 1H), 5.84 (d, J = 17.6 Hz, 1H), 5.39 (d, / = 10.8 Hz, 1H), 1.60 (s, 9H); ESIMS m/z 282.10 ([M+H]⁺); IR (thin film) 2978, 1724, 1130 cm^"1.

fert-Butyl 2-(trifluoromethyl)-4-vin lbenzoate (AI22)

The product was isolated as a colorless oil (1.2 g, 50%): ^]H NMR (400 MHz, CDC1₃) δ 7.71 (d, J = 6.4 Hz, 2H), 7.59 (d, J = 7.6 Hz, 1H), 6.77 (dd, J = 17.6, 10.8 Hz , 1H), 5.89 (d, / = 17.6 Hz, 1H), 5.44 (d, / = 10.8 Hz, 1H), 1.58 (s, 9H); ESIMS m/z 272.20 ([M+H]⁺); IR (thin film) 2982, 1727, 1159 cm^"1.

Example 5: Preparation of fert-Butyl 2-cyano-4-vinylbenzoate (AI23)

To a stirred solution of ieri-butyl 2-bromo-4-vinylbenzoate (0.5 g, 1.77 mmol) in DMF (20 mL) was added copper(I) cyanide (CuCN; 0.23 g, 2.65 mmol), and the reaction mixture was heated at 140 °C for 3 h. The reaction mixture was cooled to 25 °C, diluted with water, and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure. The residue was purified by flash chromatography (Si0₂, 100-200 mesh; eluting with 15% EtOAc in n-hexane) to afford the title compound as a white solid (0.3 g, 72%): mp 51-53 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.03 (s, 1H), 7.77 (s, 1H), 7.64 (d, / = 8.4 Hz, 1H), 6.75 (dd, / = 17.6, 10.8 Hz , 1H), 5.93 (d, / = 17.6 Hz, 1H), 5.51 (d, / = 10.8 Hz, 1H), 1.65 (s, 9H); ESIMS m/z 229.84 ([M+H]⁺); IR (thin film) 2370, 1709, 1142 cm^"1.

Example 6: Preparation of Ethyl 2- ate (AI46)

To a stirred solution of 4-iodo-2-bromobenzoic acid (5 g, 15.29 mmol) in ethyl alcohol (EtOH; 100 mL) was added sulfuric acid (H₂S0₄; 5 mL), and the reaction mixture was heated at 80 °C for 18 h. The reaction mixture was cooled to 25 °C and concentrated under reduced pressure. The residue was diluted with EtOAc (2x100 mL) and washed with water (100 mL). The combined EtOAc extracts were washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure to afford the compound as a pale yellow solid (5 g, 92%): ^]H NMR (400 MHz, DMSO-d₆) δ 8.04 (d, 7 = 1.2 Hz, 1H), 7.71 (d, 7 = 7.6 Hz, 1H), 7.51 (d, 7 = 8.4 Hz, 1H), 4.41 (q, 7 = 7.2 Hz, 2H), 1.41 (t, 7 = 7.2 Hz, 3H).

The following compounds were made in accordance with the procedures disclosed in Example 6.

Ethyl 4-bromo-2-chlorobenzoate (AI47)

The title compound was isolated as an off-white solid (2.0 g, 80 %): ^]H NMR (400 MHz, DMSO-d₆) δ 8.25 (d, 7 = 1.2 Hz, 1H), 7.79 (d, 7 = 7.6 Hz, 1H), 7.65 (d, 7 = 8.4 Hz, 1H), 4.65 (q, 7 = 7.2 Hz, 2H), 1.56 (t, 7 = 7.2 Hz, 3H).

Ethyl 4-bromo-2-methylbenzoate (AI48)

The title compound was isolated as a pale yellow liquid (3.0 g, 83%): ^]H NMR (400 MHz, CDC1₃) δ 7.79 (d, 7 = 8.4 Hz, 1H), 7.41 (s, 1H), 7.39 (d, 7 = 8.4 Hz, 1H), 4.42 (q, 7 = 7.2 Hz, 2H), 2.60 (s, 3H), 1.40 (t, 7 = 7.2 Hz, 3H)ESIMS m/z 229.11 ([M+H]⁺); IR (thin film) 1725 cm^"1.

Ethyl 4-bromo-2-fluorolbenzoate (AI49)

The title compound was isolated as a colorless liquid (9.0 g, 79%): ^]H NMR (400 MHz, DMSO-d₆) δ 7.84 (t, 7 = 8.4 Hz, 1H), 7.76 (d, 7 = 2.0 Hz, 1H), 7.58 (d, 7 = 1.6 Hz, 1H), 4.34 (q, 7 = 7.2 Hz, 2H), 1.32 (t, 7 = 7.2 Hz, 3H); ESIMS m/z 246.99 ([M+H]⁺), IR (thin film) 1734 cm^"1.

Example 7: Preparation of Ethyl 4-bromo-2-ethylbenzoate (AI50)

To a stirred solution of 4-bromo-2-fluorobenzoic acid (2.0 g, 9.17 mmol) in THF (16 mL), was added 1.0 M ethyl magnesium bromide in THF (32 mL, 32.0 mmol) dropwise at 0°C and the resultant reaction mixture was stirred at ambient temperature for 18h. The reaction mixture was quenched with 2 N HCl and extracted with ethyl acetate. The combined ethyl acetate layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford crude 4-bromo-2-ethylbenzoic acid as a colorless liquid that was used in the next step without purification (0.4 g): ^]H NMR (400 MHz, CDC1₃) δ 7.64 (d, J = 8.4 Hz, 1H), 7.47 (m, 1H), 7.43 (m, 1H), 2.95 (q, / = 4.0 Hz, 2H), 1.32 (t, / = 4.0 Hz, 3H); ESIMS m/z 228.97 ([M+H]⁺).

The title compound was synthesized from 4-bromo-2-ethylbenzoic acid in accordance to the procedure in Example 6, isolated as a colorless liquid (0.15 g, 68%): ^]H NMR (400 MHz, DMSO-d₆)5 7.90 (d, J = 8.4 Hz, 1H), 7.47 (m, 2H), 4.40 (q, J = 7.2 Hz, 2H), 3.06 (q, J = 7.6 Hz, 2H), 1.42 (t, J = 7.2 Hz, 3H), 1.26 (t, J = 7.6 Hz, 3H); ESIMS m/z 226.96 ([M-H]^"); IR (thin film) 3443, 1686, 568 cm^"1.

Example 8: Preparation of Ethyl -bromo-4-vinylbenzoate (AI51)

To a stirred solution of ethyl 2-bromo-4-iodobenzoate (5 g, 14.3 mmol) in THF/water (100 mL, 9: 1) was added potassium vinyltrifluoroborate (1.89 g, 14.3 mmol), CS2CO₃ (18.27 g, 56.07 mmol) and triphenylphosphine (0.22 g, 0.85 mmol) and the reaction mixture was degassed with argon for 20 min, then charged with PdCl₂ (0.05 g,0.28 mmol). The reaction mixture was heated to reflux for 16 h. The reaction mixture was cooled to ambient temperature and filtered through a celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate and the combined organic layers washed with water and brine, dried over Na₂S0₄ and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (Si0₂, 100-200 mesh; eluting with 2% ethyl acetate/ petroleum ether) to afford the title compound as a light brown gummy material (2 g, 56%): ^]H NMR (400 MHz, CDC1₃) δ 7.78 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 1.2 Hz, 1H), 7.51 (d, 7 = 8.4 Hz, 1H), 6.69 (dd, J = 17.6, 10.8 Hz, 1H), 5.86 (d, / = 17.6 Hz, 1H), 5.42 (d, 7 = 11.2 Hz, 1H), 4.42 (q, 7 = 7.2Hz, 2H), 1.43 (t, 7 = 3.6 Hz, 3H); ESIMS m/z 255.18 ([M+H]⁺); IR (thin film) 1729 cm^"1.

The following compounds were made in accordance with the procedures disclosed Example 8.

Ethyl 2-methyl-4-vinylbenzoate (AI52)

The title compound was isolated as a colorless liquid (0.8 g, 80 %): ^]H NMR (400 MHz, CDC1₃) δ 7.89 (d, 7 = 8.4 Hz, 1H), 7.27 (m, 2H), 6.79 (dd, 7 = 17.6, 10.8 Hz, 1H), 5.86 (d, 7 = 17.6 Hz, 1H), 5.42 (d, 7 = 11.2 Hz, 1H), 4.42 (q, 7 = 7.2 Hz, 2H), 2.60 (s, 3H), 1.43 (t, J = 1.2 Hz, 3H); ESIMS m/z 191.10 ([M+H]⁺); IR (thin film) 1717, 1257 cm^"1.

Ethyl 2-fluoro-4-vinylbenzoate (A

The title compound was isolated as a pale yellow liquid (2.0 g, 50 %): ^]H NMR (400 MHz, DMSO-d₆) δ 7.87 (t, 7 = 8.0 Hz, 1H), 7.51(d, 7 = 16.0 Hz, 1H), 7.48 (d, 7 = 16.0 Hz, 1H), 6.82 (dd, 7 = 17.6, 10.8 Hz, 1H), 6.09 (d, 7 = 17.6 Hz, 1H), 5.50 (d, 7 = 10.8 Hz, 1H), 4.35 (q, 7 = 7.2 Hz, 2H), 1.35 (t, 7 = 7.2 Hz, 3H); ESIMS m/z 195.19 ([M+H]⁺); IR (thin film) 1728 cm^"1.

Example 9: Preparation of Ethyl -chloro-4-vinylbenzoate (AI54)

To a stirred solution of ethyl 2-chloro-4-bromobenzoate (2 g, 7.63 mmol) in dimethylsulfoxide (20 mL) was added potassium vinyltrifluoroborate (3.06 g, 22.9 mmol) and potassium carbonate (3.16 g, 22.9 mmol). The reaction mixture was degassed with argon for 30 min. Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.27 g, 0.38 mmol) was added and the reaction mixture was heated to 80 °C for 1 h. The reaction mixture was diluted with water (100 mL), extracted with ethyl acetate (2 x 50 mL), washed with brine, dried over Na₂SC>4 and concentrated under reduced pressure to obtain the compound as brown gummy material (1.1 g, 69%): ^]H NMR (400 MHz, CDC1₃) δ 7.81 (d, 7 = 8.4 Hz, 1H), 7.46 (s, 1H), 7.33 (d, 7 = 8.4 Hz, 1H), 6.70 (dd, 7 = 17.6, 11.2 Hz, 1H), 5.87 (d, J = 17.6 Hz, 1H), 5.42 (d, J = 10.8 Hz, 1H), 4.41 (q, J = 7.2 Hz,2H), 1.43 (t, J = 7.2 Hz, 3H); ESIMS m/z 211.22 ([M+H]⁺); IR (thin film) 1729, 886 cm^"1.

The following compounds were made in accordance with the procedures disclosed in

Example 9.

Ethyl 2-ethyl-4-vinylbenzoate (AI

The title compound was isolated as a color less liquid (1.0 g, 66 %): ^]H NMR (300 MHz, CDC1₃) δ 7.85 (m, 1H), 7.29 (m, 2H), 6.76 (d, / = 10.8 Hz, 1H), 5.86 (d, / = 17.6 Hz, 1H), 5.36 (d, / = 10.5 Hz, 1H), 4.41 (q, / = 7.2 Hz, 2H), 3.10 (q, / = 7.2 Hz, 2H), 1.40 (t, / = 7.2 Hz, 3H), 1.30 (t, J = 7.2 Hz, 3H); ESIMS m/z 205.26 ([M+H]⁺); IR (thin film) 1720, 1607, 1263 cm^"1 _.

Methyl 2-methoxy-4-vinylbenzoate

The title compound was isolated as a pale yellow liquid (1.2 g, 75 %): ^]H NMR (400 MHz, CDCI₃) δ 7.79 (d, / = 8.0 Hz, 1H), 7.04 (d, / = 1.2 Hz, 1H), 6.97 (s, 1H), 6.74 (dd, / = 11.2, 11.2 Hz, 1H), 5.86 (d, 7 = 17.6 Hz, 1H), 5.39 (d, / = 17.6 Hz, 1H) 3.93 (s, 3H), 3.91 (s 3H). ESIMS m/z 193.18 ([M+H]⁺); IR (thin film) 1732 cm^"1 _,

Example 10: Preparation of (£ Ethyl 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l- enyl)-2-methylbenzoate (AI24

To a stirred solution of ethyl 2-methyl-4-vinylbenzoate (2.0 g, 10.5 mmol) in 1,2- dichlorobenzene (25 mL) were added l-(l-bromo-2,2,2-trifluoroethyl)-3,5-dichlorobenzene (6.44 g, 21.0 mmol), copper(I) chloride (CuCl; 208 mg, 21 mmol) and 2,2bipyridyl (0.65 g, 4.1 mmol). The reaction mixture was degassed with argon for 30 min and then stirred at 180 °C for 24 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to 25 °C and filtered, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (Si0₂, 100-200 mesh; eluting with 25-30% EtOAc in petroleum ether) afforded the title compound as a solid (1.7 g, 40%): ^]H NMR (400 MHz, CDC1₃) δ 7.91 (d, J = 8.0 Hz, 1H), 7.37 (m, 1H), 7.27-7.24 (m, 4H), 6.59 (d, J = 16.0 Hz, 1H), 6.59 (dd, / = 16.0, 8.0 Hz, 1H), 4.38 (q, / = 7.2 Hz, 2H), 4.08 (m, 1H), 2.62 (s, 3H), 1.42 (t, / = 7.2 Hz, 3H); ESIMS m/z 415.06 ([M-H]^"); IR (thin film) 1717, 1255, 1114 cm^"1.

Compounds AI25, AI57-AI68 and AC1-AC5 (Table 1) were made in accordance with the procedures disclosed in Example 10.

(£)-Ethyl 4 4,4,4 rifluoro-3-(3,4,5 richlorophenyl)but-l-enyl)-2-(trifluoromethyl)- benzoic acid (AI25)

The product was isolated as a pale brown gummy liquid (500 mg, 40%): ^]H NMR (400 MHz, CDCI₃) δ 7.79 (d, / = 8.0 Hz, 1H), , 7.71 (m, 1H), 7.61 (d, / = 7.6 Hz, 1H),7.42 (s, 2H), 6.70 (d, J = 16.0 Hz, 1H), 6.57 (dd, J = 16.0, 8.0 Hz, 1H), 4.42 (q, J = 7.2 Hz, 2H), 4.19 (m, 1H), 1.40 (t, / = 7.6 Hz, 3H),; ESIMS m/z 502.99 ([M-H]^"); IR (thin film) 1730, 1201, 1120, 749 cm^"1.

(£)-Ethyl 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-2-fluorobenzoate (AI57)

]H NMR (400 MHz, CDC1₃) δ 7.38 (s, 1H), 7.26 (s, 3H), 7.21 (d, / = 8.4 Hz, 1H), 7.16 (d, / = 11.6 Hz, 1H), 6.59 (d, / = 16.0 Hz, 1H), 6.47 (dd, / = ,16.0, 8.0 Hz, 1H), 4.41 (q, J = 6.8 Hz, 2H), 4.18 (m, 1H), 1.41 (t, J = 6.8 Hz, 3H); ESIMS m/z 419.33 ([M-H]^"); IR (thin film) 1723, 1115, 802 cm^"1.

(£)-Ethyl 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-2-bromobenzoate (AI58)

^]H NMR (400 MHz, CDCI₃) δ 7.79 (d, / = 8.0 Hz, 1H), 7.67 (s, 1H), 7.38 (m, 2H), 7.26 (m, 2H), 6.56 (d, / = 16.0 Hz, 1H), 6.45 (dd, / = 16.0, 7.6 Hz, 1H), 4.42 (q, / = 7.2 Hz, 2H), 4.39 (m, 1H), 1.42 (t, / = 7.2 Hz, 3H); ESIMS m/z 481.22 ([M-H]^"); IR (thin film) 1727, 1114, 801, 685 cm^"1.

(£ Ethyl 2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl) but-l-enyl)benzoate (AI59)

^]H NMR (400 MHz, CDC1₃) δ 7.79 (d, J = 8.0 Hz, 1H), 7.67 (d, 7 = 1.6 Hz, 1H), 7.40 (s, 2H), 7.36 (d, J = 1.6 Hz, 1H), 6.56 (d, J = 16.0 Hz, 1H), 6.44 (dd, J = 16.0, 7.6 Hz, 1H), 4.42 (q, / = 6.8 Hz, 2H), 4.15 (m, 1H), 1.42 (t, / = 6.8 Hz, 3H); ESIMS m/z 514.74 ([M-H]^"); IR (thin film) 1726, 1115, 808, 620 cm^"1.

(£ Ethyl 2-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl) but-l-enyl)benzoate (AI60)

The title compound was isolated as a light brown gummy material: ^]H NMR (400 MHz, CDCI₃) δ 7.90 (d, / = 8.8 Hz, 1H), 7.34 (d, / = 6.0 Hz, 2H), 7.25 (d, J = 1.2 Hz, 2H), 6.59 (d, / = 16.0 Hz, 1H), 6.42 (dd, / = 16.0, 8.0 Hz, 1H), 4.38 (q, / = 7.2 Hz, 2H), 4.19 (m, 1H), 2.63 (s, 3H), 1.41 (t, J = 7.2 Hz, 3H).

(£ Ethyl 2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl) but-l-enyl)benzoate (AI61)

]H NMR (400 MHz, CDC1₃) δ 7.87 (d, J = 8.0 Hz, 1H), 7.46 (d, 7 = 1.6 Hz, 1H), 7.40

(s, 2H), 7.31 (d, / = 1.6 Hz, 1H), 6.57 (d, / = 16.0 Hz, 1H), 6.44 (dd, / = 16.0 Hz„ 8.0 Hz, 1H), 4.42 (q, / = 6.8 Hz, 2H), 4.15 (m, 1H), 1.42 (t, / = 6.8 Hz, 3H); ESIMS m/z 470.73 ([M- H]^"); IR (thin film) 1726, 1115, 809, 3072 cm^"1.

(£)-Ethyl 4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)-2- (trifluoromethyl)benzoate (AI62)

The title compound was isolated as a pale brown liquid (1.0 g, 46.3 %): ^]H NMR (400 MHz, CDC1₃) δ 7.79 (d, / = 8.0 Hz, 1H), 7.71 (s, 1H), 7.61 (d, / = 7.6 Hz, 1H), 7.41 (s, 2H) 6.65 (d, / = 16.0 Hz, 1H), 6.49 (dd, / = 16.0, 8.0 Hz, 1H), 4.42 (q, / = 7.6 Hz, 2H), 4.15 (m, 1H), 1.42 (t, / = 7.6 Hz, 3H); ESIMS m/z 502.99 ([M-H]^"); IR (thin film) 1730, 1202, 1120, 750 cm^"1.

(£ Ethyl 2-chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)benzoate (AI63)

]H NMR (400 MHz, CDC1₃) δ 7.85 (d, J = 6.0 Hz, 1H), 7.46 (d, 7 = 1.8 Hz, 2H), 7.34

(m, 1H), 7.24 (m, 1H), 6.57 (d, / = 16.2 Hz, 1H), 6.45 (dd, / = 16.2, 7.2 Hz, 1H), 4.43 (q, / = 7.2 Hz, 2H), 4.13 (m, 1H), 1.41 (t, / = 7.2 Hz, 3H); ESIMS m/z 455.0 ([M+H]⁺); IR (thin film) 1728, 1115, 817 cm^"1.

(£ Ethyl 2-fluoro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)benzoate (AI64)

^]H NMR (400 MHz, CDCI₃) δ 7.93 (t, J = 7.6 Hz, 1H), 7.34 (d, J = 5.6 Hz, 2H), 7.21 (d, J = 8.0 Hz, 1H), 7.16 (d, 7 = 11.6 Hz, 1H), 6.59 (d, J = 16.0 Hz, 1H), 6.49 (dd, J = 16.0, 7.6 Hz, 1H), 4.42 (q, / = 7.6 Hz, 2H), 4.13 (m, 1H), 1.41 (t, / = 7.6 Hz, 3H); ESIMS m/z 436.81([M-H]^"); IR (thin film) 1725 cm^"1.

(£ Ethyl 2-bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)benzoate (AI65)

^]H NMR (400 MHz, CDC1₃) δ 7.94 (d, J = 8.0 Hz, 1H), 7.67 (s, 1H), 7.36 (m, 3H), 6.56 (d, / = 15.6 Hz, 1H), 6.44 (dd, / = 15.6, 8.0 Hz, 1H), 4.42 (q, / = 6.8 Hz, 2H), 4.10 (m, 1H), 1.42 (t, / = 6.8 Hz, 3H); ESIMS m/z 498.74 ([M-H]^"); IR (thin film) 1726, 1114, 820, 623 cm^"1.

(£)-Ethyl 2-methyl-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- enyl)benzoate (AI66)

The title compound was isolated as a brown semi- solid: ^]H NMR (400 MHz, CDC1₃) δ 7.90 (d, / = 8.8 Hz, 1H), 7.34 (d, J = 6.0 Hz, 2H), 7.25 (d, J = 7.2 Hz, 2H), 6.59 (d, J = 16.0 Hz, 1H), 6.42 (dd, / = 16.0 Hz, 8.0 Hz, 1H), 4.38 (q, / = 7.2 Hz, 2H), 4.19 (m, 1H), 2.63 (s, 3H), 1.41 (t, J = 7.2 Hz, 3H); ESIMS m/z 432.90 ([M-H]^"); IR (thin film) 1715 cm^"1.

(£ Methyl 2-methoxy-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- enyl)benzoate (AI67)

]H NMR (400 MHz, CDC1₃) δ 7.80 (d, J = 8.4 Hz, 1H), 7.35 (d, J = 6.0 Hz, 2H), 7.03

(d, J = 1.2 Hz, 1H), 6.92 (s, 1H), 6.59 (d, J = 15.6 Hz, 1H), 6.42 (dd, J = 15.6, 8.0 Hz, 1H), 4.13 (m, 1H), 3.93 (s, 3H), 3.88 (s, 3H); ESIMS m/z 437.29 ([M+H]⁺); IR (thin film) 1724 cm^"1.

(£ Ethyl 2-ethyl-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)benzoate (AI68)

^]H NMR (400 MHz, CDC1₃) δ 7.85 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 9.6 Hz, 2H), 7.26 (m, 1H), 7.24 (m, 1H), 6.60 (d, / = 15.6 Hz, 1H), 6.42 (dd, / = 15.6, 8.0 Hz, 1H), 4.38 (q, / = 7.2 Hz, 2H), 4.14 (m, 1H), 3.01 (q, J = 7.6 Hz 2H), 1.41 (t, J = 7.2 Hz, 3H), 1.26 (t, / = 7.6 Hz, 3H); ESIMS m/z 447.05 ([M-H]^"); IR (thin film) 1715, 1115, 817 cm^"1. Example 11: Preparation of (£')-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-2- methylbenzoic acid (AI32)

To a stirred solution of (£)-ethyl 4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-

2-methylbenzoate (1.7 g, 4.0 mmol) in 1,4-dioxane (10 mL) was added U N HC1 (30 mL), and the reaction mixture was heated at 100 °C for 48 h. The reaction mixture was cooled to 25 °C and concentrated under reduced pressure. The residue was diluted with water and extracted with chloroform (CHCI₃). The combined organic layer was dried over Na₂S0₄ and concentrated under reduced pressure, and the crude compound was washed with n-hexane to afford the title compound as a white solid (0.7 g, 50%): mp 142-143 °C; ^]H NMR (400 MHz, DMSO-rfe) δ 12.62 (br s, 1H), 7.81 (d, / = 8.0 Hz, 1H), 7.66 (s, 3H), 7.52-7.44 (m, 2H), 6.89 (dd, / = 16.0, 8.0 Hz, 1H), 6.78-6.74 (d, / = 16.0 Hz, 1H), 4.84 (m, 1H), 2.50 (s, 3H); ESIMS m/z 387.05 ([M-H] ); IR (thin film) 3448, 1701, 1109, 777 cm^"1.

Example 11.

(£)-2-Methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)benzoic acid (AI26)

The product was isolated as a pale brown gummy liquid (1 g, 46%): ^]H NMR (400 MHz, CDCI₃) δ 7.97 (d, J = 8.0 Hz, 1H), 7.77 (s, 1H), 7.65 (m, 1H), 7.41 (s, 2H), 6.68 (d, J = 16.0 Hz, 1H), 6.53 (dd, / = 16.0, 8.0 Hz, 1H), 4.16 (m, 1H), 2.50 (s, 3H); ESIMS m/z 422.67 ([M-H]^").

(£)-2-Chloro-4-(4,4,4-trifluor -3-(3,4,5-trichlorophenyl)but-l-enyl)benzoic acid (AI27)

The product was isolated as an off-white semi- solid (1 g, 45%): ^]H NMR (400 MHz, CDC1₃) δ 7.99 (d, / = 8.4 Hz, 1H), 7.50 (m, 1H), 7.40 (s, 1H), 7.36 (m, 2H), 6.59 (d, J = 15.6 Hz, 1H), 6.48 (dd, / = 15.6, 7.6 Hz, 1H), 4.14 (m, 1H); ESIMS m/z 442.72 ([M-H]^"); IR (thin film) 3472, 1704, 1113, 808 cm^"1.

(£)-2-Bromo-4-(4,4,4-trifluo -3-(3,4,5-trichlorophenyl)but-l-enyl)benzoic acid (AI28)

The product was isolated as a brown solid (1 g, 45%): mp 70-71 °C; ^]H NMR (400 MHz, CDCI₃) δ 7.99 (d, / = 8.0 Hz, 1H), 7.72 (s, 1H), 7.40 (m, 3H), 6.58 (d, / = 16.0 Hz, 1H), 6.48 (dd, / = 16.0, 8.0 Hz, 1H), 4.14 (m, 1H); ESIMS m/z 484.75 ([M-H]^"); IR (thin film) 3468, 1700 cm^"1.

(£)-2-Cyano-4-(4,4,4-trifluo -3-(3,4,5-trichlorophenyl)but-l-enyl)benzoic acid (AI29)

The product was isolated as an off-white solid (500 mg, 45%): mp 100-101 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.90 (s, 1H), 7.85 (d, J = 7.6 Hz, 1H), 7.72 (d, J = 8.0 Hz, 1H), 7.65 (br s, 1H), 7.42 (s, 2H), 6.73 (d, / = 16.0 Hz, 1H), 6.58 (dd, / = 16.0, 8.0 Hz, 1H), 4.19 (m, 1H); ESIMS m/z 431.93 ([M-H]^").

£)-4-(3-(3,4-Dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-2-methylbenzoic acid (AI30)

The product was isolated as a pale brown liquid (500 mg, 46%): ^]H NMR (400 MHz, CDCI₃) δ 8.03 (m, 1H), 7.49 (m, 2H), 7.29 (m, 1H), 7.22 (m, 2H), 6.73 (d, J = 16.0 Hz, 1H), 6.58 (dd, / = 16.0, 7.8 Hz, 1H), 4.16 (m, 1H), 2.64 (s, 3H); ESIMS m/z 386.84 ([M-H]^"); IR (thin film) 3428, 1690, 1113, 780 cm^"1.

(£')-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)-2-methylbenzoic acid (AI31)

The product was isolated as a white solid (500 mg, 50%): mp 91-93°C; ^]H NMR (400 MHz, CDC1₃) δ 8.02 (d, / = 8.0 Hz, 1H), 7.35 (d, / = 5.6 Hz, 1H), 7.30 (m, 3H), 6.61 (d, J = 16.0 Hz, 1H), 6.48 (dd, J = 16.0, 8.0 Hz, 1H), 4.13 (m, 1H), 2.65 (s, 3H); ESIMS m/z 406.87 ([M-H]-).

(£')-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)-2-(trifluoromethyl)benzoic acid (AI33)

The product was isolated as a white solid (500 mg, 45%): mp 142-143 °C; ^]H NMR (400 MHz, CDCI₃) δ 7.97 (d, / = 8.0 Hz, 1H), 7.77 (s, 1H), 7.65 (m, 1H), 7.41 (s, 2H), 6.68 (d, / = 16.0 Hz, 1H), 6.53 (dd, / = 16.0, 8.0 Hz, 1H), 4.16 (m, 1H); ESIMS m/z 474.87 ([M- H] ).

(£)-2-Bromo-4-(4,4,4-trifluo -3-(3,4,5-trichlorophenyl)but-l-enyl)benzoic acid (AI69)

The title compound was isolated as a brown solid (0.8 g, 28%): ^]H NMR (400 MHz,

CDCI₃) δ 13.42 (br, 1H), 7.98 (d, / = 1.5 Hz, 1H), 7.94 (m, 2H), 7.75 (d, / = 8.1 Hz, 1H), 7.65 (m, 1H), 7.06 (dd, J = 15.9, 9.0 Hz, 1H), 6.80 (d, J = 15.9 Hz, 1H), 4.91 (m, 1H);

ESIMS m/z 484.75 ([M-H]^"); IR (thin film) 3469, 1700 cm^"1.

(£')-2-Bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluo robut-l-enyl)benzoic acid (AI70)

The title compound was isolated as a yellow liquid (0.3 g, crude): ^]H NMR (300 MHz, CDC1₃) δ 7.79 (d, / = 8.1 Hz, 1H), 7.67 (s, 1H), 7.34 (m, 3H), 6.56 (d, / = 15.9 Hz, 1H), 6.45 (dd, / = 15.9, 7.6 Hz, 1H), 4.43 (m, 1H); ESIMS m/z 471.0 ([M-H]^").

(£')-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)-2-ethylbenzoic acid (AI71)

The title compound was isolated as a brown gummy material (0.2 g, crude): ^]H NMR (300 MHz, DMSO-d₆) δ 12.5 (br, 1H), 7.85 (d, / = 6.3 Hz, 2H), 7.75 (d, / = 8.1 Hz, 1H), 7.52 (m, 2H), 6.96 (dd, / = 8.7, 8.7 Hz, 1H), 6.78 (d, / = 15.6 Hz, 1H), 4.80 (m, 1H), 4.06 (q, / = 7.2 Hz, 2H), 1.33 (t, / = 7.2 Hz, 3H); ESIMS m/z 419.06 ([M-H]^").

(£')-2-Chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)benzoic acid (AI72)

The title compound was isolated as a yellow liquid (0.7 g, 95%): ^]H NMR (300 MHz, CDCI₃) δ 7.85 (d, / = 6.0 Hz, 1H), 7.46 (d, / = 1.8 Hz, 1H), 7.41 (s, 3H), 6.57 (d, / = 16.0 Hz, 1H), 6.45 (dd, / = 16.0, 8.0 Hz, 1H), 4.16 (m, 1H); ESIMS m/z 455.0 ([M+H]⁺); IR (thin film) 1728, 1115, 817 cm^"1.

(£')-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)-2-methylbenzoic acid (AI73)

The title compound was isolated as a light brown gummy material (0.7 g, 38%): mp 91-93 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.02 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 5.6 Hz, 1H), 7.30 (m, 3H), 6.10 (d, / = 16.0 Hz, 1H), 6.46 (dd, / = 16.0, 8.0 Hz, 1H), 4.03 (m, 1H), 2.65 (s, 3H); ESIMS m/z 406.87 ([M-H]^").

(£)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-2-fluorobenzoic acid (AI74)

The title compound was isolated as a light brown liquid (0.3 g, crude): ESIMS m/z 393.15 ([M-H]-).

')-2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l-enyl)benzoic acid (AI75)

The title compound was isolated as a light brown liquid (0.35 g, crude): ESIMS m/z 451.91 ([M-H]^").

Prophetically, compounds AI34, AI36-AI41, AI44-AI45 (Table 1) could be made in accordance with the procedures disclosed in Example 10, or Examples 10 and 11.

Example 12: Preparation of (£)-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-2- methyl-N-(2,2,2-trifluoroethyl)benzamide (AC6)

To a stirred solution of (£)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-2- methylbenzoic acid in DMF was added 2,2,2-trifluoroethylamine, 1-hydroxybenzotriazole hydrate (ΗΟΒι·Η₂0), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC^»HC1) and DIPEA, and the reaction mixture was stirred at 25 °C for 18 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na₂SC>4 and concentrated under reduced pressure. Purification by flash column chromatography (SiC½, 100-200 mesh; eluting with hexane:EtOAc afforded a white semi-solid (110 mg, 50%): ^]H NMR (400 MHz, CDC1₃) 7.40 (m, 2H), 7.26 (m, 3H), 6.56 (d, / = 16.0 Hz, 1H), 6.48 (dd, / = 16.0, 8.0 Hz, 1H), 5.82 (br s, 1H), 4.08 (m, 3H), 2.52 (s, 3H); ESIMS m/z 468.40 ([M-H]^"); IR (thin film) 1657, 1113, 804 cm^"1.

Compounds AC7-AC38, AC40-AC58, AC110-AC112, AC117, and AC118 (Table 1) were made in accordance with the procedures disclosed in Example 12. Example 13: Preparation of 4-((£')-3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-2- methyl- V-((pyrimidin-5-yl)methyl)benzamide (AC39)

To a stirred solution of (pyrimidin-5-yl)methanamine (0.15 g, 1.43 mmol) in CH₂CI₂ (10 mL) was added drop wise trimethylaluminum (2 M solution in toluene; 0.71 mL, 1.43 mmol), and the reaction mixture was stirred at 25 °C for 30 min. A solution of ethyl 4-((£)-3- (3,5-dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-2-methylbenzoate (0.3 g, 0.71 mmol) in CH₂CI₂ was added drop wise to the reaction mixture at 25 °C. The reaction mixture was stirred at reflux for 18 h, cooled to 25 °C, quenched with 0.5 N HCl solution (50 mL) and extracted with EtOAc (2 x 50 mL). The combined organic extracts were washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure. The crude compound was purified by flash chromatography (S1O₂, 100-200 mesh; eluting with 40% EtOAc in n- hexane) to afford the title compound (0.18 g, 55%): mp 141-144 °C; ^]H (400 MHz, CDC1₃) δ 9.19 (s, 1H), 8.79 (s, 2H), 7.37 (m, 2H), 7.23 (m, 2H),7.21 (m, 1H), 6.57 (d, / = 16.0 Hz, 1H), 6.40 (dd, / = 16.0, 7.6 Hz 1H), 6.21 (m, 1H), 4.65 (s, 2H), 4.11 (m, 1H), 2.46 (s, 3H); ESIMS m/z All ^'.83 ([M-H]^").

Example 14: Preparation of (£)-2-Chloro- V-(2-oxo-2-((2,2,2- trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l- l)benzamide (AC64)

To a stirred solution of glycine amide (0.15 g, 0.58 mmol) in CH₂CI₂ (5 mL) was added trimethylaluminum (2 M solution in toluene; 1.45 mL, 2.91 mmol) dropwise, and the reaction mixture was stirred at 28 °C for 30 min. A solution of (£)-ethyl 2-chloro-4-(4,4,4- trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)benzoate (0.3 g, 0.58 mmol) in CH₂CI₂ (5 mL) was added drop wise to the reaction mixture at 28 °C. The reaction mixture was stirred at reflux for 18 h, cooled to 25 °C, quenched with IN HCl solution (50 mL) and extracted with CH₂CI₂ (2 x 50 mL). The combined organic extracts were washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure. The crude compound was purified by flash chromatography (Si0₂, 100-200 mesh; eluting with 40% EtOAc in n-hexane) to afford the title compound as yellow solid (0.15 g, 50%): mp 83-85 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.72 (d, J = 8.0 Hz, 1H), 7.44 (s, 1H), 7.40 (s, 2H), 7.36 (d, J = 6.8 Hz, 1H), 7.05 (t, J = 5.2 Hz, 1H), 6.70 (t, / = 5.2 Hz, 1H), 6.57 (d, 7 = 15.6 Hz, 1H), 6.44 (dd, J = 15.6, 8.0 Hz, 1H), 4.23 (d, / = 5.6 Hz, 2H), 4.15 (m, 1H), 4.01 (m, 2H); ESIMS m/z 580.72 ([M-H]^").

Compounds AC59-AC75 (Table 1) were made in accordance with the procedures disclosed in Example 14.

Example 15: Preparation of (£')-2-Bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4- trifluorobut-l-en-l-yl)- V-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)benzamide (AC79)

To a stirred solution of (£)-2-bromo-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4- trifluorobut-l-enyl)benzoic acid (300 mg, 0.638 mmol) in CH₂C1₂ (5.0 mL) was added 2- amino-N-(2,2,2-trifluoroethyl)acetamide (172. mg, 0.638 mmol) followed by benzotriazol-1- yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) (364.5 mg, 0.701 mmol) and DIPEA (0.32 mL, 1.914 mmol), and the resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and extracted with CH₂C1₂. The combined CH₂C1₂ layer was washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure. Purification by flash column chromatography (Si0₂, 100-200 mesh; eluting with 40% ethyl acetate/ petroleum ether) afforded the title compound as an off-white solid (121 mg, 31 %): ^]H NMR (400 MHz, CDC1₃) δ 8.69 (t, / = 6.0 Hz, 1H), 8.58 (t, / = 6.0 Hz, 1H), 7.92 (s, 1H), 7.87 (d, J = 6.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 1H), 7.45 (d, J = 8.4 Hz, 1H), 7.0 (m, 1H), 6.76 (d, / = 15.6 Hz, 1H), 4.83 (t, / = 8.0 Hz, 1H), 3.98 (m, 4H); ESIMS m/z 610.97 ([M+H]⁺); IR (thin film) 3303, 1658, 1166, 817 cm^"1.

Compounds AC76-AC80, AC96-AC102, and AC113 (Table 1) were made in accordance with the procedures disclosed in Example 15.

Example 16: Preparation of (£')-4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-en-l-yl)- A⁷-(l,l-dioxidothietan-3-yl)-2-fluorobenzamide (AC83)

To a stirred solution of (£)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-2- fluoro-N-(thietan-3-yl)benzamide (100 mg, 0.2159 mmol) in acetone/ water (1 : 1, 5.0 mL) was added oxone (266 mg, 0.4319 mmol) and the resultant reaction mixture was stirred at ambient temperature for 4h. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined ethyl acetate layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure. Purification by flash column chromatography (Si0₂, 100-200 mesh; eluting with 30% ethyl acetate/ pet ether) afforded the title compound as an off white solid (70.0 mg, 66 %): ^]H NMR (400 MHz, CDC1₃) δ 8.07 (t, J = 8.4 Hz, 1H), 7.39 (t, / = 1.6 Hz, 1H), 7.31 (d, / = 1.2 Hz, 1H), 7.26 (m, 2H), 7.23 (m, 2H), 7.19 (d, / = 1.6 Hz, 1H), 6.60 (d, / = 16.8 Hz, 1H), 6.49 (dd, / = 16.8, 7.6 Hz, 1H), 4.90 (m, 1H), 4.64 (m, 2H), 4.14 (m, 2H),; ESIMS m/z 493.83 ([M-H]^"); IR (thin film) 1527, 1113, 801, 1167, 1321 cm^"1.

Compounds AC81-AC87 (Table 1) were made in accordance with the procedures disclosed in Example 16.

Example 17: Preparation of (E)- V-((5-Cyclopropyl-l,3,4-oxadiazol-2-yl)methyl)-4-(3- (3,5-dichlorophenyl)-4 4,4-trifluorobut-l-en-l-yl)-2-methylbenzamide (AC89)

A solution of (E)-N-(2-(2-(cyclopropanecarbonyl)hydrazinyl)-2-oxoethyl)-4-(3-(3,5- dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-2-methylbenzamide (200 mg, 0.379 mmol) in POCI₃ (2.0 mL) was stirred at ambient temperature for 10 min, then the resultant reaction mixture was heated to 50 °C for lh. The reaction mixture was quenched with ice water at 0 °C and extracted with ethyl acetate. The combined ethyl acetate layer was washed with saturated NaHCC^ solution and brine solution, dried over anhydrous Na₂S0₄, and concentrated under reduced pressure. Purification by flash column chromatography (Si0₂, 100-200 mesh; eluting with 50% ethyl acetate/ pet ether) afforded the title compound as a light brown gummy material (70.0 mg, 36 %): ^]H NMR (400 MHz, CDC1₃) δ 7.43 (m, 2H), 7.27 (m, 2H), 7.23 (m, 2H), 6.58 (d, / = 16.0 Hz, 1H), 6.41 (dd, / = 16.0, 7.6 Hz, 1H), 4.79 (d, / = 5.6 Hz, 2H), 4.14 (m, 1H), 2.48 (s, 3H), 2.18 (m, 1H), 1.16 (m, 4H); ESIMS mJz 509.89 ([M+H]⁺); IR (thin film) 1666, 1166, 1112, 800 cm^"1.

Example 18: Preparation of (£)-2-Bromo- V-(2-thioxo-2-((2,2,2- trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l- yl)benzothioamide (A

To a stirred solution of (£)-2-bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)- 4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)benzamide (400 mg, 0.638 mmol) in 5 mL of THF at ambient temperature was added 2,4-bis(4-methoxyphenyl)- 1,3,2,4- dithiadiphosphetane-2,4-disulfide (Lawesson's reagent) (336 mg, 0.830 mmol) in one portion. The resulting reaction mixture was stirred for 18 h. TLC showed the reaction was not complete, therefore additional Lawesson's reagent (168 mg, 0.415 mmol) was added and reaction stirred for 48 h. After the reaction was deemed complete by TLC, the reaction mixture was concentrated under reduced pressure. Purification by flash chromatography (Si0₂, 230-400 mesh; eluting with 20% EtOAc in hexanes) afforded the title compound as a yellow glassy oil (188 mg, 44.7%): ^]H NMR (400 MHz, CDC1₃) δ 8.34 (m, 1H), 8.27 (m, 1H), 7.60 (d, / = 1.6 Hz, 1H), 7.49 (d, / = 8.0 Hz, 2H), 7.40 (s, 2H), 7.36 (dd, / = 8.2, 1.7 Hz, 1H), 6.53 (d, / = 16.0 Hz, 1H), 6.38 (dd, / = 15.9, 7.9 Hz, 1H), 4.89 (d, J = 8.4, 5.5 Hz, 2H), 4.48 (qd, / = 9.0, 6.0 Hz, 2H), 4.11 (m, 1H); ESIMS m/z 656.9 ([M-H]^").

Example 19: Preparation of (£)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)phenylthioamido)-A⁷-(2,2,2-trifluoroethyl)acetamide (AC91)

To a stirred solution of (E)-2-bromo-N-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)- 4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)benzamide (400 mg, 0.638mmol) in 5 mL of THF at ambient temperature was added Lawesson's reagent (64.5 mg, 0.160 mmol) in one portion. The resulting reaction mixture was stirred for 18 h, after which time, the reaction mixture was concentrated under reduced pressure. Purification by flash chromatography (Si0₂, 230-400 mesh; eluting with 20% EtOAc in hexanes) afforded the title compounds as a yellow oil (18.5 mg, 4.51%): ^]H NMR (400 MHz, CDC1₃) δ 8.18 (t, 7 = 5.0 Hz, 1H), 7.58 (d, 7 = 1.6 Hz, 1H), 7.47 (d, 7 = 8.0 Hz, 1H), 7.40 (s, 2H), 7.34 (dd, 7 = 8.1, 1.6 Hz, 1H), 6.52 (m, 2H), 6.37 (dd, 7 = 15.9, 7.9 Hz, 1H), 4.54 (d, 7 = 4.9 Hz, 2H), 4.12 (m, 1H), 3.99 (qd, 7 = 8.9, 6.5 Hz, 2H); ESIMS m/z 640.9 ([M-H] ).

The following compound was made in accordance with the procedures disclosed in Example 19.

(E)-2-Bromo-N-(2-thioxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3- (3,4,5-trichloropheny

The product was isolated as a colorless oil (17.9 mg, 4.36%): ^]H NMR (400 MHz, CDCI₃) δ 9.16 (d, 7 = 6.1 Hz, 1H), 7.65 (d, 7 = 1.6 Hz, 1H), 7.57 (d, 7 = 8.0 Hz, 1H), 7.41 (m, 3H), 7.21 (t, 7 = 5.6 Hz, 1H), 6.55 (d, 7 = 15.9 Hz, 1H), 6.41 (dd, 7 = 15.9, 7.8 Hz, 1H), 4.59 (d, 7 = 5.6 Hz, 2H), 4.45 (qd, 7 = 9.0, 6.0 Hz, 2H), 4.12 (q, 7 = 7.2 Hz, 1H); ESIMS m/z 640.9 ([M-H] ).

Example 106: Preparation of Ethyl (Z) 2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)benzoate (AI76)

The title compound was made in accordance with the procedure disclosed in Example 88 and was isolated as a yellow viscous oil (416 mg, 23%): ^]H NMR (400 MHz, CDC1₃) δ 7.80 (d, 7 = 8.0 Hz, 1H), 7.40 (d, 7 = 1.7 Hz, 1H), 7.35 (s, 2H), 7.12 (dd, 7 = 8.0, 1.7 Hz, 1H), 6.86 (d, 7 = 11.4 Hz, 1H), 6.23 - 5.91 (m, 1H), 4.42 (q, 7 = 7.1 Hz, 2H), 4.33 - 4.10 (m, 1H), 1.42 (t, 7 = 7.2 Hz, 3H); ¹⁹F NMR (376 MHz, CDC1₃) δ -69.34 (d, 7 = 8.3 Hz); EIMS m/z 514.10 ([M]^"); IR (thin film) 2983, 1727, 1247, 1204, 1116 cm^"1.

Example 107 : Preparation of (Z)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)benzoic acid (AI77)

To a stirred solution of (Z)-ethyl 2-bromo-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)benzoate (360 mg, 0.70 mmol) in C¾CN (1.0 mL) was added iodotrimethylsilane (0.28 mL, 2.8 mmol). The reaction mixture was heated to reflux for 20 h, allowed to cool to ambient temperature and partitioned between CH₂CI₂ and aq. 10 %

Na₂S₂0₃. Organic phase was washed once with aq. 10% Na₂S₂0₃ and dried over MgS0₄ and concentrated in vacuo. Passing the material through a silica plug with 10% EtOAc in hexanes, followed by 20% MeOH in CH₂C1₂ ) as the eluting solvents afforded the title compound as a yellow foam (143 mg, 42%): mp 54-64°C; ^]H NMR (400 MHz, CDC1₃) δ 11.36 (s, 1H), 7.99 (d, 7 = 8.0 Hz, 1H), 7.43 (s, 1H), 7.30 (s, 2H), 7.14 (d, 7 = 7.9 Hz, 1H), 6.85 (d, 7 = 11.4 Hz, 1H), 6.15 (t, 7 = 10.9 Hz, 1H), 4.36 - 4.09 (m, 1H);¹⁹F NMR (376 MHz,

Example 108 : Preparation of (Z)-2-Bromo- V-(2-oxo-2-((2,2,2- trifluoroethyl)amino)ethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l- yl)benzamide (AC95)

To a stirred solution of (Z)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l- en-l-yl)benzoic acid (200 mg, 0.41 mmol) in anhydrous THF (5.0 mL) was added DCI (82 mg, 0.51 mmol). The mixture was heated in a 50 °C oil bath for 1.5 h, treated with 2-amino- N-(2,2,2-trifluoroethyl)acetamide hydrochloride (109 mg, .057 mmol) and the resulting mixture heated to reflux for 8 h. After cooling to ambient temperature, the mixture was taken up in Et₂0 and washed twice with aq. 5% NaHS0₄ (2X) and once with sat. NaCl (IX). After dying over MgS0₄, concentration in vacuo and purification by medium pressure chromatography on silica with EtOAc/Hexanes as the eluents, the title compound was obtained as a white foam (160 mg, 41%) mp 48-61°C: ^]H NMR (400 MHz, CDC1₃) δ 7.58 (d, 7 = 7.9 Hz, 1H), 7.44 - 7.29 (m, 3H), 7.14 (dd, 7 = 7.9, 1.6 Hz, 1H), 6.86 (d, 7 = 11.4 Hz, 1H), 6.76 (t, / = 5.9 Hz, 1H), 6.59 (br s, 1H), 6.21 - 6.04 (m, 1H), 4.23 (d, / = 5.5 Hz, 1H), 3.98 (qd, / = 9.0, 6.5 Hz, 2H); ¹⁹F NMR (376 MHz, CDC1₃) δ -69.31, -72.3; EIMS m/z 626.9 ([M+l]⁺).

Example 109a: Preparation of (£')-2-Bromo- V-(piperidin-4-yl)-4-(4,4,4-trifluoro-3- (3,4,5-trichlorophenyl)b -l-en-l-yl)benzamide (AC114)

( Keri-Butyl 4-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l- enyl)benzamido)piperidine-l-carboxylate (0.75 g, 1.11 mmol) was added to dioxane HCl (10 mL) at 0 °C and was stirred for 18 h. The reaction mixture was concentrated under reduced pressure and triturated with diethylether to afford the compound as a light brown solid (0.6 g, 88%).

Example 109b: Preparation of (£)- V-(l-Acetylpiperidin-4-yl)-2-bromo-4-(4,4,4- trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)benzamide (AC103)

To a stirred solution of (£)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)benzamide (0.1 g, 0.16 mmol) in CH₂CI₂ (10.0 mL) was added TEA (0.046 mL, 0.35 mmol) and stirred for 10 min. Then acetyl chloride (0.014, 0.18 mmol) was added and stirred for 16 h at ambient temperature. The reaction mixture was diluted with CH₂CI₂ and washed with saturated NaHCC>3 solution and brine solution. The combined CH₂CI₂ layer was dried over Na₂S0₄ and concentrated under reduced pressure to afford crude compound. The crude compound was washed with 5% diethyl ether / n-pentane to afford the title compound as a white solid (0.054 g, 50%).

Example 110: Preparation of (£)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)- V-(l-(3,3,3-trifluoropropanoyl)piperidin-4-yl)benzamide (AC104)

To a stirred solution of 3,3,3-trifluoropropanoic acid (0.02g, 0.16 mmol) in CH2CI2 (10.0 mL), (£)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l- enyl)benzamide (0.1 g, 0.16 mmol), PYBOP (0.09 g, 0.17 mmol), and DIPEA (0.06 g, 0.48 mmol) were added at ambient temperature. The reaction mixture was stirred at ambient temperature for 5 h. The reaction mixture was diluted with CH2CI2. The combined CH2CI2 layer was washed with 3N HC1 and saturated NaHCC>3 solution, the separated CH2CI2 layer was dried over anhydrous Na2S0₄ and concentrated under reduced pressure to afford crude compound. The crude compound was purified by column chromatography (S1O2, 100-200 mesh; eluting with 2% MeOH in CH2CI2) to afford the title compound as an off white gummy material (0.035 g, 29.%).

Example 111: Preparation of (E)-2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)-N-(l-(2,2,2-trifluoroethyl)piperidin-4-yl)benzamide

(AC105)

To a stirred solution of (£)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)benzamide (0.1 g, 0.16 mmol) in THF (5.0 mL) was added TEA (0.06 mL, 0.64 mmol) and stirred for 10 min. Then 2,2,2-trifluoroethyl

triflluoromethanesulfonate (0.03, 0.16 mmol) was added and stirred for 16 h at ambient temperature. The reaction mixture was diluted with ethyl acetate and washed with saturated NaHCC>3 solution and brine solution. The combined ethyl acetate layer was dried over Na₂S0₄ and concentrated under reduced pressure to afford the title compound as a brown solid (0.05 g, 44%). Example 112: Preparation of (£')-2-Bromo- V-(l-methylpiperidin-4-yl)-4-(4,4,4-trifluoro- 3-(3,4,5-trichlorophe

A solution of (£^')-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)benzamide (0.1 g, 0.16 mmol), formaldehyde (30% in water) (0.1 mL, 0.16 mmol) and acetic acid (0.01 mL) in MeOH (5.0 mL) was stirred at ambient temperature for 30 min. After that NaBFLCN (0.01 g, 0.16 mmol) was added at 0°C and the reaction was stirred for 8 h at ambient temperature. The solvent was removed under reduced pressure to obtain residue which was diluted with ethyl acetate and washed with saturated aq. NaHCC>3 solution and brine solution. The combined ethyl acetate layer was dried over Na₂S0₄ and concentrated under reduced pressure to obtain a residue, which was triturated with diethyl ether/ pentane to afford the title compound as a pale yellow gummy material (0.06 g, 59%).

Example 113: Preparation of ((£')-2-Bromo-/V-(l-(cyanomethyl)piperidin-4-yl)-4-(4,4,4- trifluoro-3-(3,4,5-trichl rophenyl)but-l-en-l-yl)benzamide (AC107)

To a stirred solution of (£)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)benzamide (0.25 g, 0.43 mmol) in THF (10.0 mL) was added TEA (0.16 mL, 1.29 mmol) and the reaction was stirred for 10 min. Then 2-bromoacetonitrile (0.07, 0.65 mmol) was added and the reaction was stirred for 8 h at ambient temperature. The reaction mixture was diluted with ethyl acetate and washed with saturated brine solution. The combined ethyl acetate layer was dried over Na₂S0₄ and concentrated under reduced pressure to afford the title compound as an off-white solid (0.125 g, 46.8%).

Example 114: Preparation of (£')-2-Bromo-/V-(l-(oxetan-3-yl)piperidin-4-yl)-4-(4,4,4- trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)benzamide (AC108)

A solution of (£^')-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)benzamide (0.2 g, 0.35 mmol), oxetan-3-one (0.027 g, 0.38 mmol) and acetic acid (0.01 mL) in MeOH (5.0 mL) was stirred at ambient temperature for 30 min. After that NaBH₃CN (0.022 g, 0.35 mmol) was added at 0 °C slowly lot wise over the period of 10 min and the reaction was stirred for 8 h at ambient temperature. The solvent was removed under reduced pressure to obtain a residue which was diluted with ethyl acetate and washed with saturated NaHCC>3 solution and brine solution. The combined ethyl acetate layer was dried over Na₂S0₄ and concentrated under reduced pressure to obtain a residue, which was triturated with diethyl ether/ pentane to afford the title compound as an off-white solid (0.05 g, 23%).

Example 115: Preparation of (£')-2-Bromo-/V-(l-(2-hydroxyethyl)piperidin-4-yl)-4- (4,4,4-trifluoro-3-(3,4,5- richlorophenyl)but-l-en-l-yl)benzamide (AC109)

To a stirred solution of (£)-2-bromo-N-(piperidin-4-yl)-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)benzamide (0.25 g, 0.43 mmol) in THF (10.0 mL) was added TEA (0.16 mL, 1.29 mmol) and the reaction was stirred for 10 min. Then 2-chloroethanol (0.05, 0.65 mmol) was added and the reaction was stirred for 8 h at ambient temperature. The reaction mixture was diluted with ethyl acetate and washed with saturated brine solution. The combined ethyl acetate layer was dried over Na₂S0₄ and concentrated under reduced pressure to afford the title compound as an off-white solid (0.09 g, 34%).

Example 116: Preparation of (£ 2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)benzamido)acetic acid (AI78)

To a stirred solution of (E)-tert-b tyl 2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)benzamido)acetate (440 mg, 0.734 mmol) in CH₂C1₂ (36.0 ml), was added TFA (4.0 mL) and the reaction mixture was stirred at ambient temperature for 1 h. The reaction mixture was concentrated under reduced pressure to obtain residue which was washed with n-pentane to afford the title compound as an off-white solid (310 mg, 78%): ^]H NMR (400 MHz, CDC1₃) δ 13.0 (s, 1H), 8.75 (t, / = 5.7 Hz, 1H), 7.93 (m, 2H), 7.62 (d, / = 7.5 Hz, 1H), 7.40 (d, / = 8.1 Hz, 1H), 6.96 (dd, / = 15.3, 9.3 Hz, 1H), 6.78 (d, / = 15.3 Hz, 1H), 4.83 (m, 1H), 3.90 (d, / = 5.7 Hz, 2H); ESIMS m/z 543.61([M+H]⁺); IR (thin film) 3429, 1635, 1114, 772 cm^"1.

Example 117: Preparation of (£)-AM(6-Chloropyridin-3-yl)methyl)-4-(3-(3,5- dichlorophenyl)-4,4,4-trifl robut-l-en-l-yl)-2-methylbenzothioamide (AC115)

To the stirred solution of (£^')-N-((6-chloropyridin-3-yl)methyl)-4-(3-(3,5- dichlorophenyl)-4,4,4-trifluorobut-l-enyl)-2-methylbenzamide (0.06 g, 0.117 mmol) in toluene (3 mL) was added Lawesson's reagent (0.14 g, 0.351 mmol) and the reaction was irradiated at 100 C for 1 h, then cooled to ambient temperature and concentrated under reduced pressure to provide crude compound. The crude product was purified by preparative HPLC to afford the product as yellow color solid (0.03 g, 49%).

Example 118: Preparation of (£)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut- l-en-l-yl)- V-(2-oxo-2-((2,2,2-trifluoroethyl)amino)ethyl)-2- (trifluoromethoxy)ben

Step 1. 2-(Trifluoromethoxy)-4-vinylbenzoic acid (AI79): To a stirred solution of 4-bromo-2-(trifluoromethoxy)benzoic acid (1 g, 3.67 mmol) in DMSO (20 mL) was added potassium vinyltrifluoroborate (1.47 g, 11.02 mmol) and potassium carbonate (1.52 g, 11.02 mmol). The reaction mixture was degassed with argon for 30 min.

Bistriphenylphosphine(diphenylphosphinoferrocene)palladium dichloride (0.13 g, 0.18 mmol) was added and the reaction mixture was heated to 80 °C for 1 h. The reaction mixture was diluted with water (lOOmL), extracted with ethyl acetate (2 x 50 mL), washed with brine, and dried over Na₂S0₄. Concentration under reduced pressure furnished the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.4 g, 47%): ^]H NMR (400 MHz, CDC1₃) δ 8.05 (d, 7 = 8.1 Hz, 1H), 7.44 (d, / = 1.8 Hz, 1H), 7.35 (s, 1H), 6.78 (dd, 7 =17.4.1, 11.1 Hz, 1H), 5.92 (d, / = 17.4 Hz, 1H), 5.51 (d, / = 10.8 Hz, 1H); ESIMS m/z 232.97 ([M+H]⁺).

Step 2. (£)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)-2- (trifluoromethoxy)benzoic acid (AI80): To a stirred solution of 2-(trifluoromethoxy)-4- vinylbenzoic acid (0.356 g, 1.53 mmol) in IN methyl pyrrolidine (5.0 mL) was added 1-(1- bromo-2,2,2-trifluoroethyl)-3,5-dichloro 4-fluorobenzene (1.0 g, 3.07 mmol), copper(I) chloride (CuCl; 0.03 g, 0.307 mmol) and 2,2 bipyridyl (0.095 g, 0.614 mmol). The reaction mixture was stirred at 150 °C for 1 h. After the reaction was complete by TLC, the reaction mixture was diluted with water (lOOmL) and extracted with ethyl acetate (2X 50 mL). The combined organic layers were washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure to obtain the crude compound which was purified by flash column chromatography to afford the product as pale yellow gummy material (0.3 g, 21%): ^]H NMR (400 MHz, CDCI₃) δ 8.08 (d, / = 8.0 Hz, 1H), 7.45 (d, / = 1.6 Hz, 1H), 7.35 (s, 3H), 6.63 (d, J = 16.0 Hz, 1H), 6.50 (dd, J = 16.0, 8.0 Hz, 1H), 4.15 (m, 1H); ESIMS m/z 474.81 ([M-H]^").

Step 3. (£)-4-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)- V-(2- oxo-2-(2,2,2-trifluoroethylamino)ethyl)-2-(trifluoromethoxy)benzamide (AC116) : A mixture of (£^')-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)-2- (trifluoromethoxy)benzoic acid (0.25 g, 0.52 mmol), 2-amino-N-(2,2,2- trifluoroethyl)acetamide (0.158 g, 0.62 mmol), PyBOP (0.40 g, 0.78 mmol) and DIPEA (0.134 g, 1.04 mmol) in CH₂C1₂ (10.0 mL) were stirred at ambient temperature for 16 h. The reaction mixture was diluted with water and extracted with CH₂C1₂. The combined CH₂C1₂ layer was washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure. Purification by flash column chromatography (Si0₂, 100-200 mesh; eluting with 20% ethyl acetate/ pet ether) afforded the title compound as a pale yellow gummy material (0.15 g, 47 %).

Example 20: Preparation of 5-Vinyl- -dihydro-lH-inden-l-one (BI1)

To a stirred solution of 5-bromo-2,3-dihydro-lH-inden- l-one (5 g, 23.7 mmol) in toluene were added vinylboronic anhydride pyridine complex (8.55 g, 35.54 mmol), Pd(PPh₃)₄ (0.1 g, 0.094 mmol), K₂C0₃ (22.88 g, 165.83 mmol). The resultant reaction mixture was heated at reflux for 16 h. The reaction mixture was cooled to 25 °C and filtered, and the filtrate was concentrated under reduced pressure. The residue was diluted with EtOAc and washed with water and brine. The combined organic extracts were dried over anhydrous Na₂S0₄ and concentrated under reduced pressure. The obtained residue was purified by flash column chromatography (Si0₂, 5% EtOAc in petroleum ether) afforded the title compound as a solid (1.8 g, 48%): ^]H NMR (400 MHz, CDC1₃) δ 7.74 (d, J = 7.2 Hz, 1H), 7.49 (br s, 1H), 7.44 (d, J = 7.2 Hz, 1H), 6.82 (m, 1H), 5.90 (d, J = 7.4 Hz, 1H), 5.42 (d, J = 6.4 Hz, 1H), 3.20 (m, 2H), 2.70 (m, 2H); ESIMS m/z 159.06 ([M+H]^").

The following compound was made in accordance with the procedures disclosed in Example 20.

6-Vinyl-3,4-dihydronaphthalen-l(2 -one (BI2)

The product was isolated as an off-white solid (5 g, 48%): ^]H NMR (400 MHz,

DMSO- ) δ 7.85 (d, / = 8.4 Hz, 1H), 7.48 (m, 2H), 6.82 (m, 1H), 6.02 (d, / = 7.4 Hz, 1H), 5.44 (d, / = 6.4 Hz, 1H), 2.95 (m, 2H), 2.60 (m, 2H), 2.00 (m, 2H); ESIMS m/z 173.14 ([M- H]^~); IR (thin film) 1681 cm^"1.

Example 21: Preparation of (£')-5-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)- 2,3-dihydro-lH-inden-l-one (

5-(l-Bromo-2,2,2-trifluoroethyl)-l ,2,3-trichlorobenzene (4 g, 11.7 mmol), 5-vinyl- 2,3-dihydro-lH-inden- l-one (0.92 g, 5.8 mmol), CuCl (0.115 g, 1.171 mmol) and 2,2- bipyridyl (0.053 g, 0.34 mmol) in 1,2-dichlorobenzene (25 mL) were heated at 180 °C for 16 h. The reaction mixture was cooled to 25 °C and concentrated under reduced pressure. The residue was purified by flash column chromatography (Si0₂, 5% EtOAc in petroleum ether) to afford the title compound as a liquid (1.28 g, 25%): ^]H NMR (400 MHz, CDC1₃) δ 7.76 (d, 7 = 7.4 Hz, 1H), 7.52 (m, 3H), 6.68 (d, 7 = 7.4 Hz, 1H), 6.52 (m, 1H), 4.18 (m, 1H), 3.18 (m, 2H), 2.75 (m, 2H); ESIMS m/z 419.14 ([M+H]^"); IR (thin film) 1708.94, 1113.60, 807.77 cm^"1.

The following compound was made in accordance with the procedures disclosed in Example 21.

(E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-en-l-yl)-2,3-dihydro-lH- inden-l-one (BI4)

The product was isolated as a brown semi- solid (1.2 g, 16%): ^]H NMR (400 MHz, CDCI₃) δ 7.76 (d, 7 = 7.4 Hz, 1H), 7.54 (m, 3H), 7.30 (s, 1H), 6.68 (d, 7 = 7.4 Hz, 1H), 6.52 (m, 1H), 4.18 (m, 1H), 3.18 (m, 2H), 2.75 (m, 2H); ESIMS m/z 400.84 ([M-H]^"); IR (thin film) 815, 1113, 1709 cm^"1.

(£)-6-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)-3,4-dihydronaphthalen- l(2H)-one (BI5)

The product was isolated as a pale yellow semi solid (1.2 g, 30%): ^]H NMR (400

MHz, CDCI₃) δ 8.20 (d, 7 = 8.0 Hz, 1H), 7.42 (s, 2H), 7.35 (m, 1H), 7.24 (m, 2H), 6.62 (d, 7 = 16 Hz, 1H), 6.46 (m, 1H), 4.18 (m, 1H), 2.95 (m, 2H), 2.65 (m, 2H), 2.19 (m, 2H); ESIMS m/z 432.94 ([M-H]^"); IR (thin film) 1680, 1113, 808 cm^"1.

Example 22: Preparation of (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- en-l-yl)-2-fluoro-2,3-dihydro-lH-inden-l-one (BI6)

To a stirred solution of (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- enyl)-2,3-dihydro- lH-inden- l-one (0.5 g, 1.24 mmol) in acetonitrile (20 mL), was added Selectfluor® (0.52 g, 1.48 mmol) and the reaction was heated to reflux temperature for 16 h. The reaction mixture was cooled to ambient temperature, concentrated under reduced pressure and diluted with CH₂C1₂. The solution was washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product which was purified by flash column chromatography (Si0₂, 100-200 mesh; 15% EtOAc in petroleum ether) to afford the title compound as a pale yellow semi solid (O. lg, 24%): ^]H NMR (400 MHz, CDC1₃) δ 7.80 (m, 1H), 7.48 (m, 2H), 7.32 (m, 2H), 6.65 (d, J = 16.0 Hz, 1H), 6.54 (dd, J = 16.0, 8.0 Hz, 1H), 5.38 (m, 1H), 4.18 (m, 1H), 3.62 (m, 1H), 3.32 (m, 1H); ESIMS m/z 419.06 ([M-H]^"); IR (thin film) 1728, 1114, 817 cm^"1.

Example 23: Preparation of (E)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- en-l-yl)- V-(3,3,3-trifluoropro l)-2,3-dihydro-lH-inden-l-amine (BC10)

To a stirred solution of (E)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- enyl)-2,3-dihydro- lH-inden- l-one (0.15 g, 0.35 mmol) in DCE (10 mL), was added trifluoropropyl amine (0.048 g, 0.42 mmol) and sodium cyanoborohydride (0.055 g, 0.875 mmol) in cooling and the reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was diluted with DCE, was washed with water and brine and dried over anhydrous sodium sulfate. Concentration under reduced pressure gave the crude compound, which was purified by flash column chromatography (Si0₂, 100-200 mesh; 10-15% EtOAc in petroleum ether) to afford the title compound as a colorless gummy material (0.042g, 24%): ^]H NMR (400 MHz, CDC1₃) δ 7.38-7.20 (m, 5H), 6.62 (d, / = 16.0 Hz, 1H), 6.34 (dd, J = 16.0, 8.0 Hz, 1H), 5.83 (br, 1H), 5.52 (m, 1H), 4.12 (m, 1H), 3.02 (m, 3H), 2.82 (m, 1H), 2.50 (m, 2H), 1.82 (m, 1H), 1.42 (m, 1H); ESIMS m/z 497.98 ([M-H]^"); IR (thin film) 3027, 1654, 815 cm^"1. Example 24: Preparation of 6-((£)-4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)- 3,4-dihydronaphthalen-l(2 -one oxime (BI5a)

To a stirred solution of ((£)-6-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)- 3,4-dihydronaphthalen-l(2H)-one (0.4 g, 0.92 mmol) in EtOH (50 mL) were added hydroxylamine hydrochloride (0.128 g, 1.85 mmol) and sodium acetate (0.23 g, 2.77 mmol), and the reaction mixture was heated at reflux for 3 h. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to give the crude compound, which was purified by flash column chromatography (Si0₂, 100-200 mesh; 10-15% EtOAc in petroleum ether). The title compound was isolated as a solid (0.3 g, 73%): mp 155-158 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.89 (d, / = 8.4 Hz, 1H), 7.41 (s, 2H), 7.24 (m, 1H), 7.17 (m, 1H), 6.57 (d, / = 16 Hz, 1H), 6.46 (dd, / = 16.0, 8.0 Hz, 1H), 4.13 (m, 1H), 2.82 (m, 4H), 2.04 (m, 2H); ESIMS m/z 445.95 ([M-H]^").

Example 25: Preparation of (£')-5-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)- 2,3-dihydro-lH-inden-l-amine (BI5b)

To a stirred solution of (£^')-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)-2,3- dihydro-lH-inden-l-one (1 g, 2.39 mmol) in CH₃OH (10 mL) were added ammonium acetate (1.84 g, 23.9 mmol) and sodium cyanoborohydride (NaCNB¾; 0.44 g, 7.17 mmol,) and the reaction mixture was heated at reflux for 16 h. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with water and extracted with EtOAc . The combined organic extracts were washed with water and saturated aqueous sodium

bicarbonate (satd aq NaHCC^) solution, dried over anhydrous Na₂S0₄, and concentrated under reduced pressure to afford the title compound as a liquid (500 mg, crude): ^]H NMR (400 MHz, DMSO-rfe) δ 7.85 (s, 2H), 7.40 (s, IH), 7.30 (s, 2H), 6.71 (s, 2H), 4.78 (m, IH), 4.2 (m, IH), 2.80 (m, IH), 2.73 (m, IH), 1.60 (m, 2H); ESIMS m/z 419.02 ([M+H]⁺); IR (thin film) 2924, 1552, 1112, 807 cm^"1.

The following compound was made in accordance with the procedures disclosed in Example 25.

(£)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-en-l-yl)-2,3-dihydro-lH- inden-l-amine (BI7)

The product was isolated as a light brown gummy material, taken as such to the next step (0.15 g, crude compound): ESIMS m/z 401.97 ([Μ-Η]^").

(£)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-en-l-yl)-2-fluoro-2,3- dihydro-lH-inden-l-amine (

The product was isolated as a light brown gummy material, taken as such to the next step (0.15 g, crude compound): ESIMS m/z 420.15 ([Μ-Η]^").

(£)-6-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)-l,2,3,4- tetrahydronaphthalen- 1 -ami

The product was isolated as a pale yellow liquid (500 mg crude).

Example 26: Preparation of (£)-l-Methyl-3-(5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)- but-l-enyl)-2,3-dihydro-lH-inden-l-yl)thiourea (BC1)

To a stirred solution of (£^')-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)-2,3- dihydro-lH-inden-1 -amine (0.1 g, 0.23 mmol) in Et₂0 (5 mL) was added

methylisothiocyanate (0.026 g, 0.35 mmol), and the mixture was stirred for 2 h at 25 °C. The reaction mixture was concentrated under reduced pressure, and the residue was purified by flash column chromatography (Si0₂, 20% EtOAc in petroleum ether). The title compound was isolated as a liquid (65 mg, 50%): ^]H NMR (400 MHz, CDC1₃) δ 7.39 (s, 2H), 7.25 - 7.18 (m, 3H), 6.58 (d, / = 16.0 Hz, 1H), 6.30 (dd, / = 16.0, 8.4 Hz, 1H), 5.91 - 5.70 (br, 2H), 4.05 (m, 1H), 3.05 - 2.80 (m, 6H), 2.70 (m, 1H), 1.81 (m, 1H); ESIMS m/z 492.17 ([M+H]⁺); IR (thin film) 3211, 1569, 1113, 806 cm^"1.

Compounds BC2 - BC3 in Table 1 were made in accordance with the procedures disclosed in Example 26.

Example 27: Preparation of (£)-3,3,3-Trifluoro- V-(5-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)-2,3-dihydro-lH-inden-l-yl)propanamide (BC4)

To a stirred solution of (£^')-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)-2,3- dihydro-lH-inden-1 -amine (0.1 g, 0.23 mmol) in CH₂C1₂ (10 mL) were added

trifluoropropionic acid (0.044 g, 0.34 mmol), EDC'HCl (0.038 g, 0.35 mmol), HOBf H₂0 (0.07 g, 0.46 mmol) and DIPEA (0.074 g, 0.57 mmol), and the reaction mixture was stirred for 16 h at 25 °C. The reaction mixture was diluted with CH₂C1₂ and washed with water. The combined organic layer was washed with brine, dried over anhydrous Na₂S0₄, and concentrated under reduced pressure. The crude material was purified by flash column chromatography (Si0₂, 15% EtOAc in petroleum ether) to afford the title compound as a liquid (65 mg, 65%): ^]H NMR (400 MHz, CDC1₃) δ 7.39 (s, 2H), 7.25-7.20 (m, 3H), 6.34 (d, / = 16.0 Hz, 1H), 6.30 (dd, J = 16.0, 8.0 Hz, 1H), 5.81 (br, 1H), 5.48 (m, 1H), 4.10 (m, 1H), 3.10 (m, 2H), 2.86-3.07 (m, 2H), 2.86 (m, 1H), 1.81 (m, 1H); ESIMS mJz 529.02 ([M+H]⁺); IR (thin film) 3283, 1652, 1241, 811 cm^"1.

Compounds BC5 - BC9, BC11 in Table 1 were made in accordance with the procedures disclosed in Example 27.

Example 28: Preparation of fert-Butyl 5-vinylindoline-l-carboxylate (BI10)

Step 1. 5-Bromo-indoline (Bill): To 5-Bromo-lH-indole (2.5 g, 12.82 mmol) in acetic acid (10.0 mL), NaCNB¾ (2.38 g, 38.46 mmol) was added portion wise at 10 °C over the period of 20 min. After that the reaction mixture was stirred at ambient temperature for 3 h. The reaction mixture was diluted with water and extracted with diethyl ether. The organic layer was washed with saturated NaHCC>3, water and brine solution. The combined ether layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford title compound as a pale yellow semi-solid (1.8 g, 71%).

Step 2. fert-Butyl-5-bromoindoline-l-carboxylate (BI12): To a stirred solution of 5-bromo-indoline (3.0 g , 15mmol) in acetonitrile (100 ml), was added DMAP (0.185 g ,

1.522 mmol) and di-ieri-butyl dicarbonate (3.98 g, 18.3 mmol) and the reaction was stirred at ambient temperature for 16 h. The reaction mixture was concentrated on reduced pressure to obtain a residue which was diluted with diethyl ether and washed with water and brine solution (2X). The combined ether layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford the crude product as an off-white solid, which was used in the next step without further purification (3.0 g).

Step 3. fert-Butyl-5-vinylindoline-l-carboxylate (BI10): A stirred solution of tert- butyl-5-bromoindoline-l-carboxylate (2.0 g, 6.73 mmol), potassium vinyl trifluoroborate (2.6 g, 20.20 mmol) and K₂C0₃ (2.78 g, 20.2 mmol) in DMSO (50.0 mL) was degassed with argon for 20 min at ambient temperature. PdCl₂(dppf) (0.49 g, 0.67mmol) was added at ambient temperature, then the reaction mixture was heated to 100 °C for 3 h. The reaction mixture was cooled to ambient temperature and filtered through a celite bed under vacuum and washed with diethyl ether. The reaction mixture was extracted with diethyl ether. The combined diethyl ether layer was dried over Na₂S0₄ and concentrated under reduced pressure to afford crude product. The crude compound was purified by column chromatography (Si0₂, 100-200 mesh; eluting with 2% ethyl acetate/ petroleum ether) to afford the title compound as an off-white solid (1.2 g, 73%): Mp 85.5 -88.6 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.23 (m, 3H), 6.69 (dd, / = 17.4, 10.8 Hz, 1H), 5.64 (d, / = 10.5 Hz, 1H), 5.13 (d, / = 10.5 Hz, 1H), 4.00 (t, J = 9.0 Hz, 2H), 3.10 (t, J = 9.0 Hz, 2H), 1.55 (bs, 9H).

Example 29: Preparation of (E)-tert-Butyl 5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4- trifluorobut-l-en-l-yl)ind

To a stirred solution of ieri-butyl-5-vinylindoline-l-carboxylate (1.28 g, 5.23mmol) inl,2-dichlorobenzene (10.0 mL), was added 5-(l-bromo-2,2,2-trifluoroethyl)-l,3-dichloro-2- fluorobenzene (3.4 g ,10 mmol), CuCl (103 mg, 1.05 mmol) and 2,2-bipyridyl (0.326 g, 2.092 mmol) and the resultant reaction mixture was degassed with argon for 30 min and heated to 150 °C for 1 h. The reaction mixture was cooled to ambient temperature and filtered and the filtrate was concentrated under reduced pressure. The crude compound was purified by column chromatography (S1O2, 100-200 mesh; 2% ethyl acetate/ petroleum ether) to afford the title compound as a pale yellow gummy solid (0.3 g, 61%): ^]H NMR (400 MHz,

CDCI₃) δ 7.34 (d, / = 6.0 Hz, 2H), 7.22 (s, 2H), 7.16 (d, / = 8.4 Hz, 1H), 6.52 (d, / = 16.0 Hz, 1H), 6.21 (dd, / = 16.0, 7.6 Hz, 1H), 4.07 (m, 3H), 3.10 (t, / = 8.4 Hz, 2H), 1.55 (s, 9H); ESIMS m/z 433.79 ([M-H]^"); IR (thin film) 1168, 858 cm^"1.

Example 30: Preparation of (£')-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- en-l-yl)indolin-l-amine (BI14)

Step 1. (E)- 5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)indoline (BI15) To a stirred solution of (£^')-ieri-butyl-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4- trifluorobut-l-enyl)indoline-l-carboxylate (0.2 g, 0.4 mmol) in CH2CI2 (10.0 mL) was added TFA (0.6 mL) and the reaction was stirred at ambient temperature for 2 h. The reaction mixture was diluted with CH2CI2, washed with saturated aq NaHCC>3 , water and brine solution. The separated CH2CI2 layer was dried over anhydrous Na2S0₄ and concentrated under reduced pressure to afford the crude product as a light brown gummy material which was used in the next step without further purification (0.12 g): ^]H NMR (400 MHz, CDC1₃) δ 7.33 (d, J = 6.4 Hz, 2H), 7.21 (s, 1H), 7.02 (d, J = 8.0 Hz, 1H), 6.57 (d, J = 8.4 Hz, 1H), 6.49 (d, J = 15.6 Hz, 1H), 6.21(dd, J = 15.6, 8.4 Hz, 1H), 4.07 (m, 1H), 3.61 (t, J = 8.4 Hz, 2H), 3.05 (t, J = 8.4 Hz, 2H); ESIMS m/z 389.89 ([M+H]⁺); IR (thin film) 3385, 1112, 816 cm^"1.

Step 2. 5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)-l- nitrosoindoline (BI16): To (£)- 5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- enyl)indoline (0.2 g, 0.5 mmol) in concentrated HC1 (5.0 ml) at 5 °C, was added slowly NaN0₂ in water and the reaction was allowed to stir at ambient temperature for 2 h. The reaction mixture was diluted with CH₂C1₂, and the CH₂C1₂ layer washed with water and brine solution. The separated CH₂C1₂ layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford the crude product as a pale yellow solid that was used in the next step without further purification (0.2 g): ^]H NMR (400 MHz, CDC1₃) δ 7.33 (d, J = 8.4 Hz, 1H), 7.39 (m, 4H), 6.61 (d, / = 16.0 Hz, 1H), 6.35 (dd, 7 =16.0, 8.4 Hz, 1H), 4.07 (m, 3H), 3.23 (t, J = 8.4 Hz, 2H); ESIMS m/z 418.82 ([M+H]⁺); IR (thin film) 1488, 1112, 860 cm^"1.

Step 3. (£)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-en-l- yl)indolin-l-amine (BI14): To (£)- 5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- enyl)-l -nitrosoindoline (0.1 g, 0.2 mmol) in MeOH(10.0 mL) was added zinc powder (77.5 mg) and NH₄C1 (36.9 mg, 0.69 mmol) in water (2.0 mL). The reaction mixture was stirred at ambient temperature for 3 h. The reaction mixture was diluted with CH₂C1₂ and the CH₂C1₂ layer was washed with water and brine solution. The separated CH₂C1₂ layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford the crude compound, which was purified by column chromatography (Si0₂, 100-200 mesh; eluting with 2% ethyl acetate/ petroleum ether) to afford the title compound as a light brown gummy material (0.08 g): ESIMS m/z 404.86 ([M+H]⁺).

Example 31 : Preparation of (£)-N-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4- trifluorobut-l-en-l-yl)i (BC12)

To a stirred solution of (£)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- enyl)indoline-l- amine (0.1 g, 0.247 mmol) in CH₂C1₂ (10.0 ml) was added 3,3,3- trifluoropropanoic acid (0.038 g, 0.297 mmol), PyBOP (0.192 g, 0.370 mmol) and DIPEA (0.047 g, 0.370 mmol) and the reaction was stirred at ambient temperature for 18 h. The reaction mixture was diluted with (¾(¾, and the separated CH₂CI₂ layer dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (S1O₂, 100-200 mesh; 20-25% ethyl acetate/ petroleum ether) to afford the title compound as a light brown gummy material (0.12 g, 33%): ^]H NMR (400 MHz, CDC1₃) δ 7.32, (d, 7 = 6.0 Hz, 2H) 7.28 (m, 1H), 7.20 (d, 7 = 8.0, 1H), 7.14 (d, 7 = 8.8, 1H ), 6.70 (d, 7 = 8.0 Hz, 1H), 6.60 (m, 2H), 4.15 (m, 1H), 3.85 (m, 1H), 3.65 (m, 1H), 3.46 (m, 2H), 3.19 (m, 2H); ESIMS m/z 514.86 ([M+H]⁺); IR (thin film) 3428, 1112, 857 cm^"1.

Example 32: Preparation of fert-Butyl-5-vinyl-lH-indole-l-carboxylate (BI17)

Step 1. 5-Vinyl-lH-indole (BI18): A mixture of 5-bromo-lH-indole (2.5 g, 12.82 mmol), potassium vinyltrifluoroborate (2.57 g ,19.2 mmol), CS2CO₃ (12.53 g, 38.46 mmol) and triphenylphosphine (201 mg, 0.769 mmol) in THF/water (9: 1, 75 ml) was degassed with argon for 20 min, then charged with PdCl₂ (45.3 mg,0.256 mmol). The reaction mixture was heated to reflux for 16 h, then cooled to ambient temperature, filtered through celite bed and washed with ethyl acetate. The filtrate was again extracted with ethyl acetate, and the combined organic layer washed with water and brine, dried over Na₂S0₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (S1O₂, 100-200 mesh; 2% ethyl acetate/ petroleum ether) to afford the title compound as a light brown gummy material (1.5 g, 83%): ^]H NMR (400 MHz, CDCI₃) δ 8.20 (br, 1H), 7.68 (s, 1H), 7.45 (s, 2H), 7.21 (m, 1H), 6.90 (dd, 7 =16.0, 10.8 Hz, 1H), 6.55 (m, 1H), 5.75 (d, 7 = 10.5 Hz, 1H), 5.21 (d, 7 = 10.5 Hz, 1H); ESIMS m/z 142.05 ([M-H] ).

Step 2. fert-Butyl-5-vinyl-lH-indole-l-carboxylate (BI17): To a stirred solution of

5-vinyl-lH-indole (0.7 g, 4.89 mmol) in acetonitrile (20 ml) was added DMAP (59.65 mg, 0.489 mmol) and di-ieri-butyl dicarbonate (1.38 g, 6.36 mmol), and the reaction was stirred at ambient temperature for 3 h. The reaction mixture was concentrated under reduced pressure to obtain a residue which was diluted with CH₂CI₂ and washed with water and brine solution. The combined CH₂CI₂ layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (Si0₂, 100-200 mesh; 2% ethyl acetate/ petroleum ether) to afford the title compound as an off-white semi-solid (0.7 g, 59%): ^]H NMR (400 MHz, CDC1₃) δ 8.15 (d, / = 8.0 Hz, 1H), 7.60 (s, 2H), 7.30 (d, / = 8.4 Hz, 1H), 7.21 (m, 1H), 6.90 (dd, J =16.0, 10.8 Hz, 1H), 6.59 (s, 1H), 5.75 (d, / = 10.5 Hz, 1H), 5.21 (d, / = 10.5 Hz, 1H), 1.65 (s, 9H); ESIMS m/z 242.10 ([M-H]^"); IR (thin film) 1630 cm^"1.

Example 33: Preparation of (E)4ert-Rnty\ 5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4- trifluorobut- 1-en- 1-yl)-

To a stirred solution of ieri-butyl 5-vinyl-lH-indole-l-carboxylate (0.65 g, 2.67 mmol), in 1,2-dichlorobenzene (10.0 mL) was added 5-(l-bromo-2,2,2-trifluoroethyl)-l,3- dichloro-2-fluorobenzene (1.74 g, 5.37 mmol), CuCl (53 mg, 0.537 mmol) and 2,2-bipyridyl (167 mg, 1.07 mmol). The resultant reaction mixture was degassed with argon for 30 min and heated to 150 °C for 2 h. The reaction mixture was cooled to ambient temperature and filtered, and the filtrate concentrated under reduced pressure. The crude compound was purified by column chromatography (Si0₂, 100-200 mesh; 2% ethyl acetate/ petroleum ether) to afford the title compound as a light brown gummy material (0.25 g, 10%): ^]H NMR (400 MHz, CDCI₃) δ 8.20 (d, / = 8.0 Hz, 1H), 7.60 (m, 2H), 7.39 (m, 3H), 6.69 (d, / = 16.0 Hz, 1H), 6.55 (d, / = 10.5 Hz, 1H), 6.36 (dd, / = 16.0, 8.0 Hz, 1H), 4.10 (m, 1H), 1.65 (s, 9H); ESIMS m/z 485.91 ([M-H]^"); IR (thin film) 1165, 854 cm^"1.

Example 34: Preparation of (£)-5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- en-l-yl)-lH-indole (BI20)

To a stirred solution of (E)-tert-buty\ 5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4- trifluorobut-l-enyl)-lH-indole-l-carboxylate (0.2 g, 0.40 mmol) in CH₂C1₂ (10.0 mL) was added TFA (70 mg, 0.61 mmol) and the reaction was stirred at ambient temperature for 2 h. The reaction mixture was diluted with CH₂C1₂ and washed with saturated NaHCC>3 solution, water and brine solution. The separated CH₂C1₂ layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford the title compound as a light brown solid (0.2 g, 97%): mp 132.9-138.8 °C; ^]H NMR (400 MHz, CDC1₃) δ 11.19 (br, 1H), 8.20 (d, / = 8.0 Hz, 1H), 7.60 (m, 2H), 7.39 (m, 3H), 6.69 (d, / = 16.0 Hz, 1H), 6.55 (d, / = 10.5 Hz, 1H), 6.36 (dd, 7 =16.0, 8.0 Hz, 1H), 4.82 (m, 1H); ESIMS m/z 387.98 ([M+H]⁺).

Example 35: Preparation of 4-Nitrophenyl 2-((tert-butoxycarbonyl)amino)acetate (BI21)

To a stirred solution of 4-nitrophenol (1.0 g, 7.19 mmol) in CH₂CI₂ (20.0 mL) was added N-Boc glycine (1.38 g, 7.91 mmol) and EDC HC1 (2.05 g,10.785 mmol) and the reaction was stirred at ambient temperature for 24 h. The reaction mixture was diluted with CH₂CI₂ and washed with water and saturated brine solution. The separated CH₂CI₂ layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford the title compound as a light brown gummy material that was used in the next step without further purification (1.1 g): ^]H NMR (400 MHz, CDC1₃) δ 8.29 (d, / = 9.2 Hz, 2H), 7.33 (d, / = 8.8 Hz, 2H), 5.07 (br, 1H), 4.20 (s, 2H), 1.47 (s, 9H); ESIMS m/z 296.27 ([M+H]⁺).

Example 36: Preparation of (£ fert-Butyl (2-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4- trifluorobut-l-en-l-yl)-lH-indol-l-yl)-2-oxoethyl)carbamate (BI22)

To a stirred solution of (£)-5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- enyl)-lH-indole (0.1 g, 0.258 mmol) in acetonitrile (5.0 mL) was added 4-nitrophenyl 2-(tert- butoxycarbonylamino) acetate (0.114 g, 0.387 mmol), potassium fluoride (0.03 g, 0.516 mmol), 18-crown-6-ether (0.075 g, 0.283 mmol) and DIPEA (0.0332 g, 0.258 mmol) and the reaction was stirred at ambient temperature for 16 h. The reaction mixture was concentrated to obtain a residue which was diluted with CH₂CI₂ and washed with water and brine solution. The separated (¾(¾ layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford the crude title compound as a light brown gummy material which was used in the next step without further purification (0.1 g): ESIMS m/z 545.23 ([M+H]⁺). Example 37: Preparation of (£)- V-(2-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4- trifluorobut-l-en-l-yl)-lH-indol-l-yl)-2-oxoethyl)-3,3,3-trifluoropropanamide (BC13)

Step 1. (£)-2-Amino-l-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- enyl)-lH-indol-l-yl)ethanone (BI23): To a stirred solution of (E)-tert-b ty\ 2-(5-(3-(3,5- dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)-lH-indol-l-yl)-2-oxoethylcarbamate (0.05 g, 0.09 mmol) in CH₂C1₂ (5.0 mL) was added TFA (0.01 mL) and the reaction was stirred at ambient temperature for 16 h. The reaction mixture was diluted with CH₂C1₂ and washed with saturated NaHCC>3 solution, water and brine solution. The separated CH₂C1₂ layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford the crude title compound which was used in the next step without further purification (50 mg).

Step 2. (£)- V-(2-(5-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-en-l-yl)- lH-indol-l-yl)-2-oxoethyl)-3,3,3-trifluoropropanamide (BC13): To a stirred solution of (£^')-2-amino-l-(5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-enyl)-lH-indol-l-yl) ethanone (0.04 g, 0.09 mmol) in CH₂C1₂ (5.0 ml) was added 3,3,3-trifluoropropanoic acid (17.5 mg, 0.136 mmol), PyBOP (70 mg, 0.135 mmol) and DIPEA (29 mg, 0.225 mmol) and the reaction was stirred at ambient temperature for 16 h. The reaction mixture was diluted with CH₂C1₂, and the CH₂C1₂ layer was washed with water and saturated brine solution .The separated CH₂C1₂ layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford the crude compound, which was purified by column chromatography (Si0₂, 100-200 mesh; 10% ethyl acetate/ petroleum ether) to afford the title compound as an off-white solid (30 mg, 60%): mp 121-126 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.33 (br, 1H), 7.59 (s, 1H), 7.45 (m, 4H), 6.72 (d, J = 3.6 Hz, 3H) , 6.39 (m, 1H ), 4.71 (t, J = 7.2 Hz, 2H), 4.15 (m, 1H), 3.51 (m, 1H), 3.28 (m, 1H); ESIMS m/z 553.06 ([M-H]^").

Example 38: Preparation of Ethyl 2-(l-oxo-6-vinylphthalazin-2(lH)-yl)acetate (BI24)

Step 1. 5-Bromo-3-hydroxyisoindoline-l-one (BI25): A mixture of Zn powder (1.73 g, 26.154 mmol), copper (II) sulfate pentahydrate (0.02 g ,0.08 mmol) and 2M aq NaOH (27 mL) were cooled to 0 °C. 5-Bromoisoindoline-l,3-dione (5 g, 22mmol) was added at the same temperature over the period of 30 min. The reaction mixture was stirred at 0 °C for 30 min and 3 h at ambient temperature. The reaction mixture was filtered and the filtrate was neutralized with concentrated HC1. The reaction mixture was diluted with ethanol and extracted with ethyl acetate. The combined ethyl acetate layer was dried over Na₂S0₄ and concentrated under reduced pressure to afford the crude title compound as a brown solid, which was used in the next step without further purification (1.3 g): mp 258-261°C; ^]H NMR (400 MHz, DMSO-d₆) δ 9.03 (br, 1H), 7.81 (m, 2H), 7.69 (m, 1H), 6.44 (m, 1H), 5.88 (d, J = 9.3 Hz, 1H); ESIMS m/z 225.83 ([M-H]^"); IR (thin film) 1684, 3246, 606 cm^"1.

Step 2. 6-Bromophthalazine-l(2H)-one (BI26): To a stirred solution of 5-bromo-3- hydroxyisoindoline-l-one (1.0 g, 4.40 mmol) in water, was added hydrazine hydrate (0.45 g , 8.80 mmol) and heated to 95°C for 5 h. The reaction mixture was cooled to ambient temperature, filtered and washed with diethyl ether and pentane (1: 1) to afford the title compound as a white solid that was used in the next step without further purification (0.5 g): ESIMS m/z 225.15 ([M+H]⁺).

Step 3. 6-Vinylphthalazine-l(2H)-one (BI27): A solution of 6-bromophthalazine- l(2H)-one (0.25 g, 1.11 mmol), potassium vinyl trifluoroborate (0.446 g, 3.33 mmol) and K2CO₃ (0.46 g, 3.33 mmol) in DMSO (2 mL) was degassed with argon for 20 min at ambient temperature. PdCl₂(dppf) (0.04 g, 0.055 mmol) was added at ambient temperature, and the reaction mixture was heated to 80 °C for 2 h. The reaction mixture was cooled to ambient temperature and filtered through celite bed under vacuum and washed with ethyl acetate. The reaction mixture was extracted with ethyl acetate and the combined ethyl acetate layer dried over Na₂S0₄ and concentrated under reduced pressure to afford the crude product. The crude compound was purified by column chromatography (Si0₂, 100-200 mesh; 50% ethyl acetate/ petroleum ether) to afford the title compound as a brown solid (0.12 g, 63%): ^]H NMR (400 MHz, DMSO-d₆) δ 13.61 (br, 1H), 8.33 (m, 1H), 8.19 (m, 1H), 8.01 (m, 2H), 6.97 (m, 1H), 6.15 (m, 1H), 5.56 (d, / = 10.8 Hz, 1H); ESIMS m/z 172.93 ([M+H] ⁺); IR (thin film) 1748, 1655, 3241 cm^"1.

Step 4. Ethyl-2-(l-oxo-6-vinylphthalazine-2(lH)-yl acetate (BI24): To a stirred solution of 6-vinylphthalazine-l(2H)-one (0.5 g, 2.90 mmol) in DMF (5.0 mL) was added Cs₂CC>3 (0.94 g, 2.90 mmol) and the reaction was stirred for 10 min. Ethyl bromoacetate (0.48 g,2.90 mmol) was added to the reaction mixture at ambient temperature and the reaction was stirred for 8 h at ambient temperature. The reaction mixture was diluted and extracted with ethyl acetate, and the ethyl acetate layer was washed with water and brine solution (2X). The separated ethyl acetate layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford crude product. The crude compound was purified by column chromatography (Si0₂, 100-200 mesh; 25% ethyl acetate/ petroleum ether) to afford the title compound as a brown solid (0.34 g, 45%): ^]H NMR (400 MHz, DMSO-d₆) δ 8.45 (m, 1H), 8.24 (m, 1H), 8.04 (m, 2H), 7.01 (m, 1H), 6.17 (d, / = 2.1 Hz, 1H), 5.56 (d, / = 10.8 Hz, 1H), 4.92 (s, 2H), 4.19 (m, 2H), 1.23 (m, 3H). ESIMS mJz 259.10 ([M+H] ⁺); IR (thin film) 1750, 1660 cm^"1.

Example 39: Preparation of (£ Ethyl 2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4- trifluorobut-l-en-l-yl)-l- xophthalazin-2(lH)-yl)acetate (BI28)

To a stirred solution of ethyl-2-(l-oxo-6-vinylphthalazine-2(lH)-yl acetate (0.07 g, 0.27 mmol) in 1,2-dichlorobenzene (1.0 mL) was added 5-(l-bromo-2,2,2-trifluoroethyl)-l,3- dichloro-2fluorobenzene (0.17 g, 0.54 mmol), CuCl (0.005 g, 0.05 mmol) and 2,2-bipyridyl (0.016 g, 0.10 mmol) and the resultant reaction mixture was degassed with argon for 30 min and heated to 180 °C for 12 h. The reaction mixture was cooled to ambient temperature and filtered and the filtrated was concentrated under reduced pressure. The crude compound was purified by column chromatography (Si0₂, 100-200 mesh; 10-15% ethyl acetate/ petroleum ether) to afford the title compound as a brown solid (40 mg, 29%): ^]H NMR (400 MHz,

DMSO-d₆) δ 8.40 (d, / = 8.4 Hz, 1H), 7.84 (d, / = 1.5 Hz, 1H), 7.65 (s, 1H), 7.37 (d, / = 6.3 Hz, 2H), 6.76 (d, / = 16.0 Hz, 1H), 6.59 (dd, 7 =16.0, 8.0 Hz, 1H), 4.96 (s, 2H), 4.29 (m, 3H), 1.31 (t, / = 7.2 Hz, 3H); ESIMS m/z 503.0 ([M+H] ⁺); IR (thin film) 1660, 1114, 817 cm^"1. Example 40: Preparation of (£ 2-(6-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4- trifluorobut-l-en-l-yl)-l-oxophthalazin-2(lH)-yl)acetic acid (BI29)

A solution of (£^')-ethyl-2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- enyl)-l-oxophthalazin-2(lH)-yl) acetate (0.04 g, 0.07mmol) in HQ (0.5 mL) and acetic acid (0.5 mL) was heated to 100 °C for 3 h. The solvent was removed under reduced pressure and the residue diluted with water. The aqueous layer was extracted with ethyl acetate and the separated ethyl acetate layer dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was triturated with diethyl ether-pentane mixture to afford the title compound as a brown solid (0.03 g): ^]H NMR (400 MHz, DMSO-de) δ 13.0 (br s, 1H), 8.43 (m, 1H), 8.23 (d, / = 8.1 Hz, 1H), 8.14 (m, 2H), 7.91 (m, 2H), 7.16 (dd, J =16.0, 8.0 Hz, 1H), 6.99 (d, J = 16.0 Hz, 1H), 4.96 (m, 3H),; ESIMS m/z 473.0 ([M-H]^"); IR (thin film) 1629, 1168, 817 cm^"1.

Example 41: Preparation of (£)-2-(6-(3-(3,5-Dichloro-4-fluorophenyl)-4,4,4- trifluorobut-l-en-l-yl)-l-oxophthalazin-2(lH)-yl)-N-(2,2,2-trifluoroethyl)acetamide (BC14)

To a stirred solution of (£)-2-(6-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l- enyl)-l-oxophthalazin-2(lH)-yl)acetic acid (0.15 g, 0.31 mmol) in CH₂C1₂ (20.0 ml) was added 2,2,2,-trifluoroethanamine (0.03 g, 0.31mmol), PyBOP (0.17 g, 0.34 mmol) and

DIPEA (0.15 ml, 0.93 mmol) at ambient temperature, and the reaction was stirred for 18 h. The reaction mixture was diluted with CH₂C1₂ and washed with 3N HC1 (2 x 20 mL), NaHCC>3 (2 x 20 mL) and brine solution (2x).The separated CH₂C1₂ layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to afford the crude compound. The crude compound was purified by column chromatography (Si0₂, 100-200 mesh; 20-25% ethyl acetate/ petroleum ether) to afford the title compound as a brown solid (0.11 g): mp 172-175 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.83 (t, J = 6.6 Hz, 1H), 8.42 (t, / = 14.7 Hz, 1H), 8.22 (d, / = 8.1 Hz, 1H), 8.13 (t, / = 6.3 Hz, 1H), 7.98-7.86 (m, 2H), 7.16 - 7.07 (m, 1H), 7.01 - 6.93 (m, 1H), 4.96 - 4.81 (m, 3H), 4.00 - 3.88 (m, 2H); ESIMS m/z 554.0 ([M-H]^"). Example 42: Preparation of 2-(4-Vinylbenzyl)isoindoline-l,3-dione (CI1)

To a stirred solution of l-(chloromethyl)-4-vinylbenzene (10 g, 66 mmol) in DMF (100 mL) was added potassium phthalimide (13.3 g, 72.1 mmol), and the resultant reaction mixture was heated at 70 °C for 16 h. The reaction mixture was diluted with water and extracted with CHCI₃. The combined CHCI₃ layer was washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure. Recrystallization from CH₃OH afforded the title compound as an off-white solid (8 g, 46%): ^]H NMR (400 MHz, CDC1₃) δ 7.83 (m, 2H), 7.71 (m, 2H), 7.39 (m, 4H), 6.65 (dd, J = 17.6, 10.8 Hz, 1H), 5.72 (d, J = 17.6 Hz, 1H), 5.21 (d, / = 10.8 Hz , 1H), 4.82 (s, 2H); GCMS m/z 263.2 ([M]⁺); IR (thin film) 3420, 1133, 718

-1

cm

Example 43: Preparation of (£)-2-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-en-l- yl)benzyl)isoindoline-l,3-dione (CI2)

Using the procedure of Example 10 with 2-(4-vinylbenzyl)isoindoline-l,3-dione and l-(l-bromoethyl)-3,5-dichlorobenzene as the starting materials, the title compound was isolated as an off-white solid (0.3 g, 40-50%): mp 142-145 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.86 (m, 2H), 7.74 (m, 2H ), 7.42 (m, 2H), 7.36 (m,3H), 7.27 (m, 2H), 6.58 (d, J = 16.0 Hz, 1H), 6.32 (dd, / = 16.0, 8.0 Hz, 1H), 4.82 (s, 2H), 4.05 (m, 1H); ESIMS m/z 488.17 ([M-H]^").

The following compound was made in accordance with the procedures disclosed in Example 43.

(£)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)benzyl)isoindoline-l,3- dione (CI3)

The title compound was isolated as an off white solid (0.3 g, 56%): mp 145-146 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.86 (m, 2H), 7.74 ( m, 2H ), 7.42-7.31 (m, 6H), , 6.58 (d, J = 16.0 Hz, 1H), 6.53 (dd, / = 16.0, 8.0 Hz, 1H), 4.82 (s, 2H), 4.05 (m, 1H); ESIMS m/z 522.2 ([M-H]^"); IR (thin film) 1716, 1110, 712 cm^"1.

Prophetically, compounds CI4-CI5 (Table 1) could be made in accordance with the procedures disclosed in Example 43.

Example 44: Preparation of (£')-(4-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-en-l- yl)phenyl)methanamine (CI6)

To a stirred solution of (£')-2-(4-(3-(3,5-dichlorophenyl)but-l-en-l-yl)benzyl)- isoindoline-l,3-dione (1.2 g, 2.45 mmol) in EtOH was added hydrazine hydrate (0.61 g, 12 mmol), and the resultant reaction mixture was heated at 90 °C for 1 h. The reaction mixture was filtered, and the filtrate was concentrated. The residue was dissolved in CH2CI2, washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure to afford the crude title compound as a gummy liquid (0.9 g) which was used without further purification.

The following compounds were made in accordance with the procedures disclosed in Example 44.

(£')-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)phenyl)methanamine (CI7)

The title compound was isolated and used without further purification.

Prophetically, compounds CI8-CI9 (Table 1) could be made in accordance with the procedures disclosed in Example 44.

Example 45: Preparation of 4-(Bromomethyl)-3-chlorobenzonitrile (CI10)

N

To a stirred solution of 3-chloro-4-methylbenzonitrile (5 g, 25.4 mmol) in carbon tetrachloride (CC1₄; 50 mL) under an argon atmosphere was added NBS (5.16 g, 29 mmol), and the mixture was degassed for 30 min. To this was added azobisisobutyronitrile (AIBN; 0.3 g, 1.8 mmol), and the resultant reaction mixture was heated at reflux for 4 h. The reaction mixture was cooled to ambient temperature, washed with water, and extracted with CH₂C1₂. The combined CH₂C1₂ layer was washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (Si0₂, 100-200 mesh; 5% EtOAc in n-Hexane) to afford the title compound as a white solid (4.8 g, 68%): mp 87-88 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.71 (s, 1H), 7.59 ( s, 2H ), 4.60 (s, 2H); ESIMS m/z 229.77 ([M+H]⁺); IR (thin film) 2235, 752, 621 cm^"1.

The following compounds were made in accordance with the procedures disclosed in Example 45.

4-(Bromomethyl)-3-(trifluoromethyl)benzonitrile (CI11)

The title compound was isolated as an off-white gummy material (5 g, 66%): ^]H NMR (400 MHz, CDC1₃) δ 7.96 (s, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 4.62 (s, 2H); ESIMS m/z 262.11 ([M-H]^"); IR (thin film) 2236, 1132, 617 cm^"1.

3-Bromo-4-(bromomethyl)benzonitrile (CI12)

The title compound was isolated as an off-white solid(5 g, 67%): mp 82-83 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.90 (s, 1H), 7.61 (m, 2H ), 4.62 (s, 2H); EIMS m/z 272.90; IR (thin film) 2229, 618 cm^"1.

4-(Bromomethyl)-3-fluorobenzonitrile (CI13)

N

The title compound was isolated as an off-white solid (2 g, 60%): mp 79-81 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.54 (t, J = 8.0 Hz, 1H), 7.48 (dd, J = 8.0 Hz, 8.0, 1H), 7.38 (dd, J = 5 Hz, 1H ), 4.5 (s, 2H); EIMS m/z 215.

Example 46: Preparation of 4-(Bromomethyl)-3-chlorobenzaldehyde (CI14)

To a stirred solution of 4-(bromomethyl)-3-chlorobenzonitrile (4.8 g, 17 mmol) in toluene (50 mL) at 0 °C was added dropwise diisobutylaluminum hydride (DIBAL-H, 1.0 M solution in toluene; 23.9 mL), and the reaction mixture was stirred at 0 °C for 1 h. 10 M HCl in water (5 mL) was added until the reaction mixture turned to a white slurry and then additional 1 N HCl (20 mL) was added. The organic layer was collected and the aqueous layer was extracted with CHCI₃. The combined organic layer was dried over Na₂SC>4 and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (Si0₂, 100-200 mesh; 5% EtOAc in n-Hexane) to afford the title compound as a white solid (3.8 g, 80%): mp 64-66 °C; ^]H NMR (400 MHz, CDC1₃) δ 10.00 (s, IH), 7.92 (s, IH), 7.78 (d, / = 8.0 Hz, IH), 7.64 (d, / = 8.0 Hz, IH), 4.60 (s, 2H); ESIMS m/z 232.78 ([M+H]⁺).

The following compounds were made in accordance with the procedures disclosed in Example 46.

4-(Bromomethyl)-3-(trifluoromethyl)benzaldehyde (CI15)

The title compound was isolated as a pale yellow low-melting solid (5 g, 60%): ^]H NMR (400 MHz, CDC1₃) δ 10.09 (s, IH), 8.19 (s, IH), 8.09 (m, IH), 7.81 (m, IH), 4.61 (s, 2H); ESIMS m/z 265.04 ([M-H]^"); IR (thin film) 1709, 1126, 649 cm^"1.

3-Bromo-4-(bromomethyl)benzaldehyde (CI16)

The title compound was isolated as a pale yellow solid (5 g, 62%): mp 94-95 °C; ^]H NMR (400 MHz, CDC1₃) δ 9.96 (s, IH), 8.05 (s, IH), 7.81 (d, / = 8.0 Hz, IH), 7.62 (d, / = 8.0 Hz, IH), 4.60 (s, 2H); EIMS m/z 275.90.

4-(Bromomethyl)-3-fluorobenzaldehyde (CI17)

The title compound was isolated as an off-white solid (5 g, 61%): mp 43-45 °C; ^]H NMR (400 MHz, CDC1₃) δ 9.1 (s, IH), 7.54 (t, / = 8 Hz, IH), 7.48 (d, / = 8 Hz, IH), 7.38 (d, J = 5 Hz, IH ), 4.5 (s, 2H); EIMS m/z 216.

Example 47: Preparation of 3-chloro-4-((l,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (CI18)

To a stirred solution of 4-(bromomethyl)-3-chlorobenzaldehyde (3.8 g, 14 mmol) in DMF (40 mL) was added potassium pthalimide (3.54 g, 19.14 mmol), and the mixture was heated at 60°C for 6 h. The reaction mixture was cooled to ambient temperature and diluted with water (100 mL). The solid obtained was separated by filtration and dried under vacuum to afford the title compound as a white solid (2.8 g, 60%): mp 123-126 °C; ^]H NMR (400 MHz, CDC1₃) δ 9.95 (s, IH), 8.21 (s, IH), 7.91 (m, 3H), 7.80 (m, 2H), 7.20 (m, IH), 5.05 (s, 2H); ESIMS m/z 298.03 ([M-H] ).

The following compounds were made in accordance with the procedures disclosed in Example 47.

4-((l,3-Dioxoisoindolin-2-yl)-3-(trifluoromethyl)benzaldehyde (CI19)

The title compound was isolated as an off white solid (1 g, 62%): mp 142-143 °C; H

NMR (400 MHz, CDC1₃) δ 10.05 (s, IH), 8.15 (s, IH), 7.91 (m, 2H), 7.80 (m, 3H), 7.27 (m, IH), 5.19 (s, 2H); ESIMS m/z 332.03 ([M-H]^").

3-Bromo-4-((l,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (CI20)

The title compound was isolated as an off-white solid (0.5 g, 64%): mp 159-161 °C; ^]H NMR (400 MHz, CDCI₃) δ 9.95 (s, IH), 8.21 (s, IH), 7.91 (m, 3H), 7.80 (m, 2H), 7.20 (m, IH), 5.05 (s, 2H); ESIMS m/z 314.00 ([M-CHO]^").

4-((l,3-Dioxoisoindolin-2-yl)-3-fluorobenzaldehyde (CI21)

The title compound was isolated as a white solid (2 g, 60%): mp 154-156 °C; ^]H NMR (400 MHz, CDC1₃) δ 9.95 (s, 1H), 7.9 (m, 2H), 7.75 (m, 2H), 7.6 (m, 2H), 7.5 (t, / = 7.6 Hz, 1H), 5.05 (s, 2H); EIMS m/z 283.1.

Example 48: Preparation of 2-(2-Chloro-4-vinylbenzyl)isoindoline-l,3-dione (CI22)

To a stirred solution of 3-chloro-4-((l,3-dioxoisoindolin-2-yl)methyl)benzaldehyde (2.8 g, 8.2 mmol) in 1,4-dioxane (30 mL) were added K₂C0₃ (1.68 g, 12.24 mmol) and methyl triphenyl phosphonium bromide (4.37 g, 12.24 mmol) at ambient temperature. Then the resultant reaction mixture was heated at 100 °C for 18 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the obtained filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (Si0₂, 100-200 mesh; 20% EtOAc in n-Hexane) to afford the title compound as a white solid (1.94 g, 70%): mp 141-143 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.85 (m, 2H), 7.70 (m, 2H), 7.41 (m, 1H), 7.21 (m, 2H), 6.71 (dd, / = 17.6, 10.8 Hz, 1H), 5.72 (d, J = 17.6 Hz, 1H), 5.23 (d, J = 10.8 Hz, 1H), 4.92 (s, 2H); ESIMS m/z 298.10 ([M-H] )·

The following compounds were made in accordance with the procedures disclosed in Example 48.

2-(2-(Trifluoromethyl)-4-vinylbenzyl)isoindoline-l,3-dione (CI23)

The title compound was isolated as a light brown solid (0.5 g, 60%): mp 134-135 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.92 (m, 2H), 7.80 (m, 2H), 7.71 (s, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.16 (d, / = 8.0 Hz, 1H), 6.65 (m, 1H), 5.80 (d, / = 17.8 Hz, 1H), 5.19 (d, / = 10.8 Hz, 1H), 5.09 (s, 2H); ESIMS m/z 332.10 ([M+H]⁺).

2-(2-Bromo-4-vinylbenzyl)isoindoline-l,3-dione (CI24)

The title compound was isolated as an off white solid (0.5 g, 62%): mp 126-128 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.92 (m, 2H), 7.79 (m, 2H), 7.62 (s, 1H), 7.21 (m, 1H), 7.16 (d, / = 8.0 Hz, 1H), 6.62 (m, 1H), 5.72 (d, / = 17.8 Hz, 1H), 5.15 (d, / = 10.8 Hz, 1H), 4.95 (s, 2H); EIMS m/z 341.10.

2-(2-Fluoro-4-vinylbenzyl)isoindoli -l,3-dione (CI25)

The title compound was isolated as a white solid (0.5 g, 61%): mp 140-142 °C; H

NMR (400 MHz, CDC1₃) δ 7.85 (m, 2H), 7.72 (m, 2H), 7.25 (m, 1H), 7.11 (m, 2H), 6.63 (: 1H), 5.80 (d, J = 17.6 Hz, 1H), 5.28 (d, J = 10.8 Hz, 1H), 4.92 (s, 2H); EIMS m/z 282.08. Example 49: Preparation of (£)-2-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4- trifluorobut-l-en-l-yl)benzyl)isoindoline-l,3-dione (CI26)

To a stirred solution of 2-(2-chloro-4-vinylbenzyl)isoindoline-l,3-dione (2.0 g, 6.51 mmol) in 1,2-dichlorobenzene (25 mL) were added l-(l-bromo-2,2,2-trifluoroethyl)-3,5- dichlorobenzene (3.48 g, 11.36 mmol), CuCl (112 mg, 1.13 mmol) and 2,2- bipyridyl (0.35 g). The resultant reaction mixture was degassed with argon for 30 min and then was stirred at 180 °C for 24 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (Si0₂, 100-200 mesh; 25-30% EtOAc in n-hexane) to afford the title compound as solid (1.3 g, 50%): mp 141-143 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.92 (m, 2H), 7.79 (m, 2H), 7.42 (m, 2H), 7.24 (m, 2H), 7.20 (m, 2H), 6.54 (d, / = 16.0 Hz, 1H), 6.34 (dd, / = 16.0, 8.0 Hz, 1H), 5.00 (s, 2H), 4.10 (m, 1H); ESIMS m/z 524.07 ([M+H]⁺).

Example 49.

(£)-2-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l- yl)benzyl)isoindoline-l,3-d

The title compound was isolated as a pale white solid (0.2 g, 55%): mp 128-129 °C;

^]H NMR (400 MHz, CDC1₃) δ 7.92 (m, 2H), 7.79 (m, 2H), 7.42 (m, 3H), 7.22 (m, 2H), 6.52 (d, / = 16.0 Hz, 1H), 6.32 (dd, / = 16.0, 8.0 Hz, 1H), 5.00 (s, 2H), 4.05 (m, 1H); ESIMS m/z 557.99 ([M+H]⁺).

(£)-2-(2-Chloro-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-l-en-l- yl)benzyl)isoindoline-l,3-di

The title compound was isolated as an off white solid (0.2 g, 54%): mp 177-180 °C; ^]H NMR (400 MHz, CDCI₃) δ 7.90 (m, 2H), 7.77 (m, 2H), 7.42 (s, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.21 (m, 2H), 6.52 (d, / = 16.0 Hz, 1H), 6.32 (dd, / = 16.0, 8.0 Hz, 1H), 5.00 (s, 2H), 4.05 (m, 1H); ESIMS m/z 540.08 ([M-H]^"); IR (thin film) 1716 cm^"1.

(£)-2-(2-Chloro-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-l-en-l- yl)benzyl)isoindoline-l,3-dione (CI29)

The title compound was isolated as an off-white solid (0.2 g, 59%): ^]H NMR (400 MHz, CDC1₃) δ 7.89 (m, 2H), 7.76 (m, 2H), 7.47 (m, 3H), 7.21 ( m, 3H), 6.50 (d, / = 16.0 Hz, IH), 6.32 (dd, / = 16.0, 7.6 Hz, IH), 4.97 (s, 2H), 4.11 (m, IH); ESIMS m/z 522.27 ([M- H]^~); IR (thin film) 3064, 1717, 1111, 715 cm^"1.

(£)-2-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-en-l-yl)-2-(trifluoromethyl)- benzyl)isoindoline-l,3-dione

The title compound was isolated as an off-white solid (0.2 g, 54%): mp 141-142 °C; ^]H NMR (400 MHz, CDC1₃) 7.94 (m, 2H), 7.80 (m, 2H), 7.69 (s, IH), 7.44 ( m, IH), 7.38 (m, IH), 7.24 (m, 2H), 7.19 ( m, IH ), 6.60 (d, / = 16.0 Hz, IH), 6.39 (dd, / = 16.0, 7.6 Hz, IH), 5.10 (s, 2H), 4.11 (m, IH); ESIMS m/z 556.00 ([M-H]^").

(£)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)-2-(trifluoromethyl)- benzyl)isoindoline-l,3-dione

The title compound was isolated as an off-white solid (0.2 g, 56%): mp 130-132 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.94 (m, 2H), 7.80 (m, 2H), 7.69 (s, IH), 7.44 (m, 3H), 7.19 (m, IH), 6.61 (d, / = 16.0 Hz, IH), 6.38 (dd, / = 16.0, 7.6 Hz, IH), 5.10 (s, 2H), 4.12 (m, IH); ESIMS m/z 589.57 ([M-2H]^").

(£)-2-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)benzyl)- isoindoline-l,3-dione (CI32)

The title compound was isolated as a pale yellow solid (0.2 g, 55%): mp 160-162 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.92 (m, 2H), 7.80 (m, 2H), 7.62 (s, IH), 7.39 (s, 2H), 7.24 (m, IH), 7.16 (m, IH), 6.52 (d, / = 16.0 Hz, IH), 6.32 (dd, / = 16.0, 8.0 Hz, IH), 4.98 (s, 2H), 4.12 (m, IH); ESIMS m/z 599.78 ([M-H]^").

(£)-2-(2-Fluoro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)benzyl)- isoindoline-l,3-dione (CI33)

The title compound was isolated as an off-white solid (0.2 g, 55%): mp 72-74 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.88 (m, 2H), 7.74 (m, 2H), 7.38 (s, 2H), 7.34 (m, IH), 7.18 (m,

2H), 6.54 (d, / = 16.0 Hz, IH), 6.32 (dd, / = 16.0, 8.0 Hz, IH), 4.91 (s, 2H), 4.08 (m, IH);

ESIMS m/z 539.89 ([M-H]^"); IR (thin film)1773 cm^"1.

Prophetically, compounds CI34-CI41 (Table 1) could be made in accordance with the procedures disclosed in Example 49.

Example 50: Preparation of (£)-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut- l-en-l-yl)phenyl)methanamine (CI42)

To a stirred solution of (£)-2-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut- l-en-l-yl)benzyl)isoindoline-l,3-dione (0.4 g, 0.76 mmol) in EtOH was added hydrazine hydrate (0.38 g, 7.6 mmol), and the resultant reaction mixture was heated at 80 °C for 2 h. The reaction mixture was filtered, and the filtrate was concentrated. The residue was dissolved in CH₂CI₂, washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure to afford the title compound as a gummy liquid (0.3 g), which was carried on to the next step without further purification.

The following compounds were made in accordance with the procedures disclosed in Example 50.

(£)-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)phenyl)- methanamine (CI43)

The product obtained in this reaction was carried on to the next step without further purification.

(£)-(2-Chloro-4-(3-(3,4-dichlorophenyl)-4,4,4-trifluorobut-l-en-l-yl)phenyl)- methanamine (CI44)

The product obtained in this reaction was carried on to the next step without further purification.: ^]H NMR (400 MHz, CDC1₃) δ 7.48 (d, J = 8.4 Hz, 2H), 7.39 (m, 2H), 7.23 (m, 2H), 6.52 (d, / = 16.0 Hz, 1H), 6.38 (dd, / = 16.0, 7.6 Hz, 1H), 4.12 (m, 1H), 3.90 (s, 2H); ESIMS m/z 391.90 ([M-H]^"); IR (thin film) 3370, 3280, 1111, 817 cm^"1.

(£)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)-2-(trifluoromethyl)- phenyl)methanamine (CI45)

The title compound was isolated as a gummy material. The product obtained reaction was carried on to the next step without further purification.

(£)-(2-Bromo-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l-en-l-yl)phenyl)- methanamine (CI46)

The title compound was isolated as a gummy material: The product obtained reaction was carried on to the next step without further purification.

(£)-(2-Bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)phenyl)- methanamine (CI47)

(£)-(2-Fluoro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)phenyl)- methanamine (CI48)

The title compound was isolated as a gummy material: ^]H NMR (400 MHz, CDC1₃) δ 7.40 (s, 2H), 7.33 (t, / = 7.6 Hz, IH), 7.13 (m, 2H), 6.56 (d, / = 16.0 Hz, IH), 6.33 (dd, / = 16.0, 7.6 Hz, IH), 4.08 (m, IH), 3.90 (s, 2H); ESIMS m/z 413.84 ([M+H]⁺); IR (thin film) 3368, 3274, 1114, 808 cm^"1.

Prophetically, compounds CI49-CI57 (Table 1) could be made in accordance with the procedures disclosed in Example 50. Example 51: Preparation of 3-Chloro-4-((pyridin-2-ylamino)methyl)benzaldehyde (CI58)

To a stirred solution of 4-(bromomethyl)-3-chlorobenzaldehyde (2 g, 9 mmol) in N,N- dimethylacetamide (DMA; 20 mL) was added K₂C0₃ (2.36 g, 17.16 mmol) and 2- aminopyridine (0.84 g, 8.58 mmol), and the reaction mixture was stirred at ambient temperature for 4 h. The reaction mixture was diluted with water and extracted with EtOAc The combined organic layer was washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure. The residue was purified by flash column chromatography (Si0₂, 100-200 mesh; 20% EtOAc in n-Hexane) to afford the title compound as off-white solid

(1.05 g, 50%): mp 122-123 °C; ^]H NMR (400 MHz, CDC1₃) δ 9.94 (s, 1H), 8.11 (s, 1H), 7.88 (s, 1H), 7.72 (d, J = 4.8 Hz, 1H), 7.62 (d, J = 5.7 Hz, 1H), 7.4 (m, 1H), 6.64 (d, J = 3.9 Hz, 1H), 6.38 (d, / = 6.3 Hz, 1H), 5.04 (br s, 1H), 4.71 (s, 2H); ESIMS m/z 246.97 ([M+H]⁺). Example 52: Preparation of V-(2 pyridin-2-amine (CI59)

To a stirred solution of 3-chloro-4-((pyridin-2-ylamino)methyl)benzaldehyde (1 g, 4. mmol) in 1,4-dioxane (20 mL) were added K CO₃ (0.84 g, 6.09 mmol) and methyl triphenyl phosphonium bromide (2.17 g, 6.09 mmol) at ambient temperature. Then the resultant reaction mixture was heated at 100 °C for 18 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the obtained filtrate was concentrated under reduced pressure. The residue was purified by flash chromatography (Si0₂, 100-200 mesh; 10% EtOAc in n-Hexane) to afford the title compound as a white solid (0.5 g, 50%): mp 119-121 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.12 (s, 1H), 7.42 - 7.40 (m, 3H), 7.26 (s, 1H), 6.66 (m, 2H), 6.36 (d, J = 6.3 Hz, 1H), 5.75 (d, J = 13.2 Hz, 1H), 4.92 (br s, 1H), 4.60 (s, 2H); ESIMS m/z 245.05 ([M+H]⁺).

Example 53: Preparation of Ethyl 2-amino-2-(5-bromo-3-chloropyridin-2-yl)acetate (CI60)

Ethyl 2-(diphenylmethyleneamino)acetate (10.2 g, 38.2 mmol) was added to sodium hydride (NaH; 3.18 g, 133.52 mmol) in DMF (50 mL) at 0 °C, and the mixture was stirred for 30 min. To this was added 5-bromo-2,3-dichloropyridine (12.9 g, 57.23 mmol), and the reaction mixture was stirred for 3 h at ambient temperature. The reaction mixture was quenched with 2 N HCl solution and then stirred for 4 h at ambient temperature. The mixture was extracted with EtOAc. The combined EtOAc layer was washed with brine, dried over anhydrous Na₂SC>4, and concentrated under reduced pressure. Purification by flash column chromatography (20-30% EtOAc in hexane) afforded the title compound as a liquid (1.3 g,

20%): ^]H NMR (400 MHz, CDC1₃) δ 8.52 (s, 1H), 7.89 (s, 1H ), 5.09 (slH), 4.23 (m, 2H), 2.27 (br s, 2H), 1.26 (m, 3H); ESIMS m/z 293.05 ([M+H]⁺); IR (thin film) 3381, 3306, 1742, 759, 523 cm^"1.

Example 54: Preparation of (5-Bromo-3-chloropyridin-2-yl)methanamine

hydrochloride (CI61)

A stirred solution of ethyl 2-amino-2-(5-bromo-3-chloropyridin-2-yl)acetate (0.5 g, 1.7 mmol) in 3 N HCl (25 mL) was heated at reflux for 4 h. The reaction mixture was washed with diethyl ether and water. The combined ether layer was concentrated under reduced pressure to afford the title compound as an off-white solid (400 mg, 65%): ^]H NMR (400 MHz, CDC1₃) δ 8.78 (s, 1H), 8.70 (br s, 2H), 8.45 (s, 1H), 4.56 (m, 2H); ESIMS m/z 221.15 «M+H]⁺).

Example 55: Preparation of 2-((5-Bromo-3-chloropyridin-2-yl)methyl)isoindoline-l,3- dione (CI62)

To a stirred solution of (5-bromo-3-chloropyridin-2-yl)methanamine hydrochloride 1.4 mmol) in toluene (40 mL) was added TEA (0.41 g, 4.08 mmol) and phthalic anhydride (0.24 g, 1.63 mmol), and the reaction mixture was heated at reflux for 2 h. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with water and extracted with EtOAc . The combined EtOAc layer was washed with brine, dried over anhydrous Na₂S0₄, and concentrated under reduced pressure. The residue was purified by column chromatography (20-30% EtOAc in hexane) to afford the title compound as a white solid (0.25 g, 65%): ^]H NMR (400 MHz, CDC1₃) δ 8.78 (s, 1H), 8.45 (s, 1H), 7.88 (m, 2H), 7.74 ( m, 2H), 4.56 (m, 2H); ESIMS m/z 349 ([M-H]^"); IR (thin film) 3307, 1665, 1114, 813 cm^"1.

Example 56: Preparation of 2-((3-Chloro-5-vinylpyridin-2-yl)methyl)isoindoline-l,3- dione (CI63)

To a stirred solution of 2-((5-bromo-3-chloropyridin-2-yl)methyl)isoindoline-l,3- dione (0.23 g, 0.65 mmol) in toluene (10 mL) were added Pd(PPh₃)₄ (3.7 mg, 0.003 mmol), K2CO₃ (0.269 g, 1.95 mmol) and vinyl boronic anhydride pyridine complex (0.78 g, 3.28 mmol), and the reaction mixture was heated at reflux for 16 h. The reaction mixture was filtered, and the filtrate was washed with water and brine, dried over anhydrous Na₂S0₄, and concentrated under reduced pressure. Purification by flash column chromatography (20-30% EtOAc in hexane) afforded the title compound as an off-white solid (0.2 g, 65%): ^]H NMR

(400 MHz, CDCI₃) δ 8.30 (s, 1H), 7.91 (m, 2H), 7.77 (m, 3H), 7.72 (m, 1H), 6.63 (m, 5.79 (d, / = 16.0 Hz, 1H), 5.39 (d, / = 16.0 Hz, 1H), 5.12 (s, 2H); ESIMS m/z 299.20 «M+H]⁺).

Example 57: Preparation of (£)-2-((3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichloro- phenyl)but-l-en-l-yl)pyridi -2-yl)methyl)isoindoline-l,3-dione (CI64)

To a stirred solution of 2-((3-chloro-5-vinylpyridin-2-yl)methyl)isoindoline-l,3-dione (0.35 g, 1.17 mmol) in 1 ,2-dichlorobenzene (10 mL) were added 5-(l-bromo-2,2,2- trifluoroethyl)-l,2,3-trichlorobenzene (0.8 g, 2.3 mmol), CuCl (23 mg, 0.12 mmol), 2,2- bipyridyl (0.073 g, 0.234 mmol), and the reaction mixture was heated at 180 °C for 16 h. The reaction mixture was concentrated under reduced pressure and purified by column chromatography (20-30% EtOAc in hexane) to afford the title compound as a liquid (0.4 g, 50%): mp 79-82 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.27 (s, 1H), 7.91 (m, 2H), 7.77 (m, 3H), 7.36 (s, 2H), 6.51 (d, / = 15.6 Hz, 1H), 6.32 (dd, / = 15.6, 8.0 Hz, 1H), 5.30 (s, 2H), 4.13 (m, 1H); ESIMS m/z 559 ([M+H]⁺).

Example 58 : Preparation of (£)-(3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)pyridin-2-yl)methanamine (CI65)

To a stirred solution of (£)-2-((3-chloro-5-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)pyridin-2-yl)methyl)isoindoline-l,3-dione (200 mg, 0.358 mmol) in EtOH (5 mL) was added hydrazine hydrate (89.6 mg, 1.79 mmol), and the reaction mixture was heated at reflux for 2 h. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in CH₂C1₂. The organic layer was washed with water and brine, dried over anhydrous Na₂S0₄, and concentrated under reduced pressure to afford the title compound as a solid (100 mg). The product obtained in this reaction was carried on to the next step without further purification.

Example 59: Preparation of 4-(Bromomethyl)-l-naphthonitrile (CI66)

To a stirred solution of 4-methyl-l-naphthonitrile (5 g, 30 mmol) in CC1₄ (50 mL) under argon atmosphere was added NBS (6.06 g, 34.09 mmol), and the reaction mixture was degassed for 30 min. AIBN (0.3 g, 2.1 mmol) was added, and the resultant reaction mixture was heated at reflux for 4 h. The reaction mixture was cooled to ambient temperature, diluted with water and extracted with CH₂C1₂ (3 x 100 mL). The combined CH₂C1₂ layer was washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure. The residue was purified by flash column chromatography (Si0₂, 100-200 mesh; 5% EtOAc in n-Hexane) to afford the title compound as a white solid (3.8 g, 52%): mp 131-133 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.33 (m, 1H), 8.24 (m, 1H), 7.88 (d, / = 8.0 Hz, 1H), 7.78 (m, 2H), 7.62 (d, / = 8.0 Hz, 1H), 4.95 (s, 2H); ESIMS m/z 245.92 ([M+H]⁺); IR (thin film) 2217 cm^"1.

Example 60: Preparation of 4-(Bromomethyl)-l-naphthaldehyde (CI67)

To a stirred solution of 4-(bromomethyl)-l-naphthonitrile (8 g, 33mmol) in toluene (100 mL) at 0 °C was added dropwise DIBAL-H (1.0 M solution in toluene; 43 mL), and the reaction mixture was stirred at 0 °C for 1 h. 3 N HC1 in water (50 mL) was added to the mixture until it became a white slurry and then additional 1 N HC1 (20 mL) was added. The organic layer was collected and the aqueous layer was extracted with EtOAc (3 xlOO mL). The combined organic layer was dried over Na₂S0₄ and concentrated under reduced pressure. Purification by flash column chromatography (Si0₂, 100-200 mesh; 5% EtOAc in petroleum ether) afforded the title compound as a white solid (7 g, 88%): mp 115-116 °C; ^]H NMR (400 MHz, CDCI₃) δ 10.41 (s, 1H), 9.35 (m, 1H), 8.22 (m, 1H), 7.90 (d, / = 8.0 Hz, 1H), 7.75 (m, 3H), 4.95 (s, 2H); ESIMS m/z 248.88 ([M+H]⁺).

Example 61: Preparation of 4-((l,3-Dioxoisoindolin-2-yl)methyl)-l-naphthaldehyde (CI68)

To a stirred solution of 4-(bromomethyl)-l-naphthaldehyde (7 g, 28. mmol) in DMF

(100 mL) was added potassium phthalimide (7.3 g, 39.5 mmol), and the mixture was heated at 85 °C for 2 h. The reaction mixture was cooled to ambient temperature and diluted with water (100 mL). The obtained solid was separated by filtration and dried under vacuum to afford the title compound as a white solid (8.8 g, 98%): mp 190-192 °C; ^]H NMR (400 MHz, CDCI₃) δ 10.39 (s, 1H), 9.25 (m, 1H), 8.41 (m, 1H), 8.10 (d, / = 8.0 Hz, 1H), 7.95 (m, 4H), 7.80 (m, 4H), 7.61 (m, 4H), 5.39 (s, 2H); ESIMS mJz 316.09 ([M+H]⁺); IR (thin film) 1708 cm^"1.

Example 62: Preparation of 2-((4-Vinylnaphthalen-l-yl)methyl) isoindoline-l,3-dione (CI69)

To a stirred solution of 4-((l,3-dioxoisoindolin-2-yl)methyl)-l-naphthaldehyde (9 g, 28.5 mmol) in 1,4-dioxane (100 mL) were added K2CO₃ (6 g, 42.8 mmol) and methyl triphenyl phosphonium bromide (15.3 g, 35.7 mmol) at ambient temperature. The reaction mixture was heated at 100 °C for 14 h and then was cooled to ambient temperature. The reaction mixture was filtered, and the obtained filtrate was concentrated under reduced pressure. Purification by flash chromatography (Si0₂, 100-200 mesh; 20% EtOAc in petroleum ether) afforded the title compound as a white solid (6 g, 67%): mp 146-147 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.35 (m, 2H), 7.95 (m, 4H), 7.65 (m, 4H), 7.39 (m, 1H), 5.81 (m, 1H), 5.45 (m, 1H), 5.21 (s, 2H); ESIMS mJz 314.13 ([M+H]⁺).

Example 63: Preparation of (£)-2-((4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en- l-yl)naphthalen-l-yl)methyl)isoindoline-l,3-dione (CI70)

To a stirred solution of 2-((4-vinylnaphthalen-l-yl)methyl)isoindoline-l,3-dione (1.5 g, 4.79 mmol) in 1,2-dichlorobenzene (15 mL) were added l-(l-bromo-2,2,2-trifluoroethyl)- 3,4,5-trichlorobenzene (3.2 g, 9.5 mmol), CuCl (24 mg, 0.24 mmol) and 2,2-bipyridyl (0.149 g, 0.95 mmol), and the resultant reaction mixture was degassed with argon for 30 min and then stirred at 180 °C for 14 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (Si0₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) afforded the title compound as an off-white solid (1.5 g, 56%): mp 158-160 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.40 (m, 1H), 7.89 (m, 2H), 7.74 (m, 2H), 7.64 (m, 2H), 7.58 (m, 2H), 7.46 (s, 2H), 7.36 (m, 2H), 6.31 (m, 1H), 5.30 (s, 2H), 4.21 (m, 1H); ESIMS m/z 572.08 ([M-H] ).

Example 64: Preparation of (£)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l- yl)naphthalen-l-yl)methanamine (CI71)

To a stirred solution of (£)-2-((4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l- yl)naphthalen-l-yl)methyl)isoindoline-l,3-dione (0.4 g, 0.7 mmol) in EtOH was added hydrazine hydrate (0.18 g, 3.5 mmol), and the resultant reaction mixture was heated at 80 °C for 2 h. The reaction mixture was filtered, and the filtrate was concentrated. The residue was dissolved in CH2CI2, and the solution was washed with brine, dried over Na₂SC>4, and concentrated under reduced pressure. The title compound was isolated as a gummy liquid (150 mg, 50%). The product obtained in this reaction was carried on to the next step without further purification.

Example 65: Preparation of 2-((4-Bromophenyl)amino)isoindoline-l,3-dione (CI72)

To a stirred solution of (4-bromophenyl)hydrazine hydrochloride (0.5 g, 2.2 mmol) in glacial acetic acid (8 mL) was added phthalic anhydride (0.398 g, 2.690 mmol), and the reaction mixture was stirred at 130 °C for 1 h under a nitrogen atmosphere. The reaction mixture was quenched with satd aq. NaHCC>3 solution and filtered to give a solid. Purification by column chromatography (Si0₂, 0-10% EtOAc in petroleum ether) afforded the title compound as a solid (60 mg, 84%): mp 205-206 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.71 (s, 1H), 7.99 (m, 4H), 7.32 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 8.8 Hz, 2H); ESIMS m/z 314.95 ([M-H]^").

Example 66: Preparation of 2-((4-Vinylphenyl)amino)isoindoline-l,3-dione (CI73)

To a solution of 2-(4-bromophenylamino)isoindoline-l,3-dione (2 g, 6. mmol) in 1,2- dimethoxyethane (20 mL) and water (4 mL) were added vinyl boronic anhydride pyridine complex (4.57 g, 18.98 mmol) and K₂C0₃ (1.3 g, 9.5 mmol) followed by Pd(PPh₃)₄ (0.219 g, 0.189 mmol). The resultant reaction mixture was heated at 150 °C in a microwave for 30 min and then was concentrated under reduced pressure. Purification by column chromatography (Si0₂, 15% EtOAc in petroleum ether) afforded the title compound as a solid (200 mg, 13%): mp 174-176 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.65 (s, 1H), 7.94 (m, 4H), 7.29 (d, / = 8.4 Hz, 2H), 6.72 (d, 7 = 8.4 Hz, 2H), 6.61 (m, 1H), 5.61 (d, / = 17.6 Hz, 1H), 5.05 (d, / = 11.2 Hz, 1H); ESIMS m/z 263.18 ([M-H] ).

Example 67: Preparation of (£)-2-((4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en- l-yl)phenyl)amino)isoind

To a stirred solution of 2-(4-vinylphenylamino)isoindoline-l,3-dione (0.3 g, 1.1 mmol) in 1,2-dichlorobenzene (5 mL) were added CuCl (0.022 g, 0.273 mmol), 2,2-bipyridyl (0.07 g, 0.46 mmol) and 5-(l-bromo-2,2,2-trifluoroethyl)-l,2,3-trichlorobenzene (0.77 g, 2.27 mmol). The reaction mixture was degassed with argon for 30 min and was heated at 180 °C for 2 h. The reaction mixture was then concentrated under reduced pressure, and the residue was purified by column chromatography (Si0₂, 0-30% EtOAc in petroleum ether) to afford the title compound as a solid (450 mg, 75%): mp 187-189 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.75 (s, 1H), 7.96 (m, 4H), 7.82 (s, 2H), 7.37 (d, / = 8.8 Hz, 1H), 6.73 (d, / = 8.4 Hz, 2H), 6.61 (m, 2H), 6.58 (m, 1H), 4.59 (m, 1H); ESIMS m/z 523.05 ([M-H]^").

Example 68: Preparation of (£)-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l- yl)phenyl)hydrazine (CI75)

To a stirred solution of (£)-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l- enyl)phenylamino)isoindoline-l,3-dione (0.16 g, 0.31 mmol) in EtOH (5 mL), was added hydrazine hydrate (0.076 g, 1.52 mmol), and the reaction mixture was heated at 85 °C for 1 h. The reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure to afford the title compound as a solid (0.08 g, 66%) which was carried on to the next step without further purification.

Example 69: Preparation of 2-(4-Vinylphenoxy)isoindoline-l,3-dione (CI76)

To a stirred solution of 4-vinylphenylboronic acid (2 g, 13 mmol), 2- hydroxyisoindoline-l,3-dione (3.63 g, 24.53 mmol), and CuCl (1.214 g 12.26 mmol) in 1,2- dichloroethane (50 mL) was added pyridine (1.065 g, 13.48 mmol), and the resultant reaction mixture was stirred at ambient temperature for 48 h. The reaction mixture was diluted with water and extracted with CHCI₃. The combined CHCI₃ layer was washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure. Purification by flash column chromatography (Si0₂; 20% EtOAc in petroleum ether) afforded the title compound as a white solid (2 g, 63%): mp 129-131 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.93 (d, J = 2.0 Hz, 2H), 7.82 (d, J = 3.2 Hz, 2H), 7.38 (d, J = 2.0 Hz, 2H), 7.14 (d, J = 2.0 Hz, 2H), 6.70 (m, 1H), 5.83 (d, / = 16.0 Hz, 1H), 5.22 (d, / = 10.8 Hz, 1H); ESIMS m/z 266.12 ([M+H]⁺). Example 70: Preparation of (£)-2-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en- l-yl)phenoxy)isoindoline- -dione (CI77)

To a stirred solution of 2-(4-vinylphenoxy)isoindoline-l,3-dione (0.3g, 1.1 mmol) in 1,2-dichlorobenzene (10 mL) was added l-(l-bromoethyl)-3,4,5-trichlorobenzene (769 mg, 2.26 mmol), CuCl (22 mg, 0.22mmol) and 2,2-bipyridyl (35 mg, 0.44 mmol), and the resultant reaction mixture was degassed with argon for 30 min and heated to 180 °C for 24 h. The reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. The crude material was purified by column

chromatography (Si0₂, 100-200 mesh; 20% EtOAc in petroleum ether) to afford the title compound as a solid (0.29 g, 50%): ^]H NMR (400 MHz, CDC1₃) δ 7.90 (m, 1H), 7.62 (m, 2H), 7.50 (m, 1H), 7.40 (s, 2H), 7.12 (s, 1H), 6.90 (m, 2H), 6.60 (m, 2H), 6.20 (m,lH), 4.08 (m, 1H); ESIMS m/z 524.09 ([M-H] ).

Example 71: Preparation of (£)-0-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en- l-yl)phenyl)hydroxylamine

To a stirred solution of (£)-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l- enyl)phenoxy)isoindoline-l,3-dione (0.2 g, 0.4 mmol) in EtOH was added hydrazine hydrate (0.1 g, 1.9 mmol), and the resultant reaction mixture was heated at 90 °C for 1 h. The reaction mixture was filtered, and the filtrate was concentrated. The residue was dissolved in CH₂C1₂. washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure to afford the crude title compound as a gummy liquid (0.08 g, 53%): ^]H NMR (400 MHz, CDC1₃) δ 7.40 (s, 2H), 6.98 (s, 1H), 6.82 (s, 2H), 6.48 (m, 1H), 6.20 (m, 1H), 5.02 (s, 1H), 4.08 (m, 1H); ESIMS m/z 394.94 ([M-H]^").

Example 72: Preparation of (£)- V-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l- enyl)benzyl)acetamide (CC

To a stirred solution of (£)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l- en-l-yl)phenyl)methanamine (0.3 g, 0.8 mmol) in CH₂C1₂ (10 mL) was added acetic anhydride (0.12 mL, 1.14 mmol), and TEA (0.217 mL, 1.52 mmol), and the resultant reaction mixture was stirred at ambient temperature for 6 h. The reaction mixture was diluted with water and extracted with CH₂C1₂. The combined CH₂C1₂ layer was washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure. Purification by flash column chromatography (Si0₂, 100-200 mesh; 30-50% ethyl acetate in hexane) afforded the title compound as an off-white solid (0.2 g, 60%) mp 107-109 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.37 (m, 3H), 7.28 (m, 4H), 6.60 (d, / = 16.0 Hz, 1H), 6.36 (dd, / = 16.0, 8.0 Hz, 1H), 5.75 (br s, 1H), 4.46 (d, / = 6 Hz, 2H), 4.01 (m, 1H), 2.11 (s, 3H); ESIMS m/z 402.00 ([M+H]⁺).

Compounds CC2 - CC6 in Table 1 were made in accordance with the procedures disclosed in Example 72. In addition, compound DC56 in Table 1 was made from compound DC55 in accordance with the procedures disclosed in Example 72.

Example 73: Preparation of (£)- V-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4- trifluorobut-l-en-l-yl)benzyl)acetamide (CC7)

To a stirred solution of (£)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l- en-l-yl)phenyl)methanamine (0.3 g, 0.8 mmol) in DMF (5 mL) was added 2,2,2-trifluoro- propanoic acid (97 mg, 0.76 mmol), HOBfH₂0 (174 mg, 1.14 mmol) and EDC'HCl (217 mg, 1.14 mmol) and DIPEA (196 mg, 1.52 mmol), and the resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure. Purification by flash column

chromatography (Si0₂, 100-200 mesh; ethyl acetate in hexane (30-50% afforded the title compound as an off-white solid (0.2 g, 60%): mp 127-128 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.42 (m, 4H), 7.24 (m, 2H), 6.53 (d, J = 16.0 Hz, 1H), 6.36 (dd, J = 16.0, 8.0 Hz, 1H) , 5.86 (br s, 1H), 4.51 (d, / = 6.0 Hz, 2H), 4.05 (m, 1H), 2.02 (s, 3H); ESIMS m/z 436.03 ([M+H]⁺).

Compounds CC8 - CC28 in Table 1 were made in accordance with the procedures disclosed in Example 73.

Example 74: Preparation of (^)-iV-(Pyridin-2-ylmethyl)-iV-(4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)-2-(trifluoromethyl)benzyl)cyclopropanecarboxamide

(CC29)

Step 1 : (£)-l-(Pyridin-2-yl)- V-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l- enyl)-2-(trifluoromethyl)benzyl)methanamine. (E)-(4-(4,4,4-Trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)-2-(trifluoromethyl)phenyl)methanamine (0.46 g, 1 mmol) was dissolved in CH₃OH (3 mL). To this was added pyridine-2-carbaldehyde (0.107 g, 1 mmol). The reaction mixture was stirred for 1 h. After 1 h, NaBH₄ (0.076 g, 2 mmol) was added and left at ambient temperature for 3 h. The reaction mixture was concentrated to give an oily residue. Purification by flash column chromatography (Si0₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as a pale yellow liquid (0.22 g, 40%): ^]H NMR (400 MHz, CDC1₃) δ 8.58 (d, /= 4.8 Hz, 1H), 7.74 (m, 1H), 7.62 (m, 2H), 7.52 (m, 1H), 7.4 (s,

2H), 7.3 (m, 1H), 7.2 (m, 2H), 6.60 (d, / = 16.0 Hz, 1H), 6.38 (dd, / = 16.0, 8.0 Hz, 1H), 4.10 (m, 1H), 4.02 (s, 2H), 3.96 (s, 2H); ESIMS m/z 552.95 ([M+H]⁺); IR (thin film) 3338, 1114, 808 cm^"1.

Step 2 : (£)- V-(Pyridin-2-ylmethyl)- V-(4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)-2-(trifluoromethyl)benzyl)cyclopropanecarboxamide. (£^")- l-(Pyridin-2-yl)-N-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)-2- (trifluoromethyl)benzyl)methanamine (0.27 g, 0.05 mmol) was taken up in CH₂C1₂ (3 mL). To this was added TEA (0.14 mL, 0.1 mmol). The reaction mixture was stirred for 10 min. After 10 min, the reaction mixture was cooled to 0 °C, and cyclopropylcarbonyl chloride (0.08 mL, 0.075 mmol) was added. The reaction mixture was stirred at ambient temperature for 1 h and then was washed with water and satd aq NaHCC>3 solution. The organic layer was dried over anhydrous Na₂S0₄ and evaporated to obtain pale yellow gummy material (0.15 g, 50%): ^]H NMR (400 MHz, CDC1₃) δ 8.58 (d, J = 4.6 Hz, 1H), 7.74 (m, 1H), 7.62 (m, 2H), 7.52 (m, 1H), 7.4 (s, 2H), 7.3 (m, 1H), 7.2 (m, 2H), 6.60 (d, / = 16.0 Hz, 1H), 6.38 (dd, / = 16.0, 8.0 Hz, 1H), 5.02 (s, 1H), 4.8 (s, 1H), 4.8 (d, 7 = 10 Hz, 2H), 4.10 (m, 1H), 1.8 (m, 1H), 1.2 (m, 2H), 0.6 (m, 2H); ESIMS m/z 620.86 ([M-H]^"); IR (thin film) 1645, 1115, 808 cm^"1. Example 75: Preparation of (£)- V-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)benzyl)-3-(methylsulfonyl)propanamide (CC30)

(£^')-N-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)benzyl)-3- (methylthio)propanamide (0.15 g, 0.28 mmol) was treated with oxone (0.175 g, 0.569 mmol) in 1 : 1 acetone: water (20mL) for 4 h at ambient temperature. The acetone was evaporated to obtain a white solid (0.095 g, 60%): mp 101-104 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.41 (m, 4H), 7.24 (m, 1H), 6.53 (d, / = 16.0 Hz, 1H), 6.35 (dd, / = 16.0, 8.0 Hz, 1H), 6.12 (br s, 1H), 4.53 (m, 2H), 4.10 (m, 1H), 3.42 (m, 2H), 2.91 (s, 3H), 2.78 (m, 2H); ESIMS mJz 559.75 ([M-H]-).

Example 76: Preparation of (£)-l-(2-Chloro-4-(3-(3,5-dichlorophenyl)-4,4,4- trifluorobut-l-en-l-yl)benzyl)-3-ethylurea (CC31)

To a stirred solution of (£)-(2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l- en-l-yl)phenyl)methanamine (0.2 g, 0.5 mmol) in CH₂CI₂ (5 mL) at 0 °C were added TEA (0.141 mL, 1 mmol) and ethylisocyanate (0.053 g, 0.75 mmol), and the reaction mixture was stirred for 1 h at 0 °C. The reaction mixture was diluted with CH₂CI₂. The organic layer was washed with water and brine, dried over Na₂S0₄, and concentrated under reduced pressure. Purification by column chromatography (S1O₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as a solid (0.141 g, 60%): mp 177-178 °C; ^]H NMR (400 MHz, CDCI₃) δ 7.58 (m, 2H), 7.41 (m, 3H), 7.24 (m, 1H), 6.53 (d, / = 16.0 Hz, 1H), 6.35 (dd, / = 16.0, 8.0 Hz, 1H), 4.70 (br s, 1H), 4.43 (s, 2H), 4.08 (m, 1H), 3.21 (m, 2H), 1.25 (m, 3H); ESIMS m/z 463 ([M-H]^").

Compounds CC32 - CC35 in Table 1 were made in accordance with the procedures disclosed in Example 76.

Example 77: Preparation of (£ 3-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en- -yl)benzyl)-l,l-dimethylurea (CC36)

To a stirred solution of (£^')-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut- l-en-l-yl)phenyl)methanamine (0.2 g, 0.5 mmol) in CH₂CI₂ (5 mL) at 0 °C were added TEA (0.141 mL, 1 mmol) and N,N-dimethylcarbamoyl chloride (0.08 g, 0.075 mmol), and the reaction mixture was stirred for 1 h at 0 °C. The reaction mixture was diluted with (¾(¾. The organic layer was washed with water and brine, dried over Na₂S0₄, and concentrated under reduced pressure. Purification by column chromatography (S1O₂, 100-200 mesh; 30- 50% EtOAc in hexane) afforded the title compound as a solid (0.15 g, 60%): ^]H NMR (400 MHz, CDCI₃) δ 7.39 (m, 4H), 7.28 (m, 1H), 6.54 (d, / = 16.0 Hz, 1H), 6.34 (dd, / = 16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d, / = 6.0 Hz, 2H), 4.10 (m, 1H), 2.9 (s, 3H), 2.7 (s, 3H); ESIMS m/z 497 ([M-H]^"); IR (thin film) 3350, 1705, 1114, 808 cm^"1.

Example 78: Preparation of (£)-l-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en- -yl)benzyl)-3-ethylthiourea (CC37)

To a stirred solution of (£)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut- l-en-l-yl)phenyl)methanamine (0.2 g, 0.5 mmol) in CH₂CI₂ (5 mL) at 0 °C were added TEA (0.141 mL, 1 mmol) and ethyl isothicyanate (0.053 g, 0.75 mmol), and the reaction mixture was stirred for 1 h at 0 °C. The reaction mixture was diluted with CH₂CI₂. The organic layer was washed with water and brine, dried over Na₂S0₄, and concentrated under reduced pressure. Purification by column chromatography (S1O₂, 100-200 mesh; 30-50% EtOAc in hexane) afforded the title compound as a solid (0.14 g, 60%): mp 88-91 °C; ^]H NMR (400 MHz, CDCI₃) δ 7.49 (d, / = 8 Hz, 1H), 7.41 (d, J = 7.2 Hz, 2H), 7.26 (m, 2H), 6.50 (d, / = 16 Hz, 1H), 6.35 (dd, / = 16.0, 8.0 Hz, 1H), 6.0 (br s, 1H), 5.73 (br s, 1H), 4.80 (br s, 2H), 4.09 (m, 1H), 1.23 (m, 3H); ESIMS m/z 515.01 ([M+H]⁺).

Compound CC38 in Table 1 was made in accordance with the procedures disclosed in Example 78.

Example 79: Preparation of (£ fert-Butyl (2-chloro-4-(3-(3,5-dichlorophenyl)-4,4,4- trifluorobut-l-en-l-yl)benzyl)-3-ethylurea (CC39)

To a stirred solution of (£^')-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut- l-en-l-yl)phenyl)methanamine (0.2 g, 0.5 mmol in CH₂CI₂ (5 mL) at 0 °C were added TEA (0.141 mL, 1 mmol) and di-ieri-butyl dicarbonate (0.163 mL, 0.75 mmol), and the reaction mixture was stirred for 4 h at ambient temperature. The reaction mixture was diluted with CH₂CI₂. The organic layer was washed with water and brine, dried over Na₂S0₄, and concentrated under reduced pressure. Purification by column chromatography (S1O₂, 100-200 mesh; 10-20% EtOAc in hexane) afforded the title compound as a white solid (0.147 g, 60%): ^]H NMR (400 MHz, CDC1₃) δ 7.39 (m, 4H), 7.28 (m, 1H), 6.54 (d, / = 16.0 Hz, 1H), 6.34 (dd, / = 16.0, 8.0 Hz, 1H), 4.97 (br s, 1H), 4.38 (d, / = 6.0 Hz, 2H), 4.10 (m, 1H), 1.53 (s, 9H); ESIMS m/z 526.09 ([M-H]^"); IR (thin film) 3350, 1705, 1114, 808 cm^"1.

Compound CC40 in Table 1 was made in accordance with the procedures disclosed in Example 79.

Example 80: Preparation of (£ Methyl 2-((2-chloro-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en- -yl)benzyl)amino)-2-oxoacetate (CC41)

To a stirred solution of (£)-(2-chloro-4-(3-(3,4,5-trichlorophenyl)-4,4,4-trifluorobut- l-en-l-yl)phenyl)methanamine (0.2 g, 0.5 mmol) in CH₂CI₂ (5 mL) at 0 °C were added TEA (0.141 mL, 1 mmol) and methyl 2-chloro-2-oxoacetate (0.09 g, 0.75 mmol), and the reaction mixture was stirred for 1 h at 0 °C. The reaction mixture was diluted with CH₂CI₂. The organic layer was washed with water and brine, dried over Na₂S0₄, and concentrated under reduced pressure. Purification by column chromatography (S1O₂, 100-200 mesh; 20% EtOAc in hexane) afforded the title compound as a solid (0.12 g, 50%): ^]H NMR (400 MHz, CDC1₃) δ 7.48 (m, 1H). 7.43 (m, 3H), 7.38 (m, 1H), 7.23 (s, 1H), 6.55 (d, / = 16.0 Hz, 1H), 6.36 (dd, / = 16.0, 8.0 Hz, 1H), 4.60 (d, / = 4.4 Hz, 2H), 4.18 (m, 1H), 3.85 (s, 3H); ESIMS m/z 512.22 ([M-H]^"); IR (thin film) 1740, 1701, 1114, 808 cm^"1.

Example 81: Preparation of (£)- V¹-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l- -l-yl)benzyl)- V²-(2,2,2-trifluoroethyl)oxalamide (CC42)

To a stirred solution of 2,2,2-trifluoroethylamine hydrochloride (0.1 g, 0.77 mmol) in CH₂CI₂ (10 mL) was added dropwise trimethylaluminum (2 M solution in toluene; 0.39 mL, 0.77 mmol), and the reaction mixture was stirred at 25 °C for 30 min. A solution of (£)- methyl 2-((2-chloro-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)benzyl)-2- oxoacetate (0.2 g, 0.38 mmol) in CH₂CI₂ (5 mL) was added dropwise to the reaction mixture at 25 °C. The reaction mixture was stirred at reflux for 18 h, cooled to 25 °C, quenched with 0.5 N HC1 solution (50 mL) and extracted with EtOAc (2 x 50 mL). The combined organic extracts were washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure. The crude compound was purified by flash chromatography (S1O₂, 100-200 mesh; 20%-40% EtOAc in n-hexane) to afford the title compound (0.13 g, 60%): mp 161-163 °C; ^]H NMR (400 MHz, DMSO- ) δ 9.45 (br s, 2H), 7.90 (s, 2H), 7.75 (s, IH), 7.46 (s, IH), 7.28 (s, IH), 6.93 (m, IH), 6.75 (m, IH), 4.80 (m, IH), 4.40 (s, 2H), 3.90 (s, 2H); ESIMS m/z 578.96 ([M-H]^").

Example 82: Preparation of (£)- V-(2-Chloro-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)benzyl)pyridin-2-amine (CC43)

To a stirred solution of N-(2-chloro-4-vinylbenzyl)pyridin-2-amine (0.3 g, 1.22 mmol) in 1 ,2-dichlorobenzene (5 mL) were added 5-(l-bromo-2,2,2-trifluoroethyl)-l,2,3- trichlorobenzene (0.83 g, 2.44 mmol), CuCl (24 mg, 0.24 mmol) and 2,2-bipyridyl (76 mg, 0.48 mmol). The resultant reaction mixture was degassed with argon for 30 min and then stirred at 180 °C for 24 h. After the reaction was deemed complete by TLC, the reaction mixture was cooled to ambient temperature and filtered, and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (S1O₂, 100-200 mesh; 15% EtOAc in n-hexane) afforded the title compound as an off-white solid (0.2 g, 35%): mp 140-

142 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.11 (d, / = 4.0 Hz, IH), 7.40 (m, 5H), 7.22 (m, IH), 6.61 (m, 2H), 6.35 (m, 2H), 4.94 (br s, IH), 4.61 (d, / = 6.4 Hz, 2H), 4.11 (m, IH); ESIMS m/z 505.39 ([M+H]⁺).

Example 83: Preparation of (£)- V-((3-Chloro-5-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)-but-l-en-l-yl)pyridin-2-yl)methyl)-3,3,3-trifluoropropanamide (CC44)

To a stirred solution of (£)-(3-chloro-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but- l-en-l-yl)pyridin-2-yl)methanamine (0.1 g, 0.2 mmol) in CH₂CI₂ (5 mL) were added 3,3,3- trifluoropropanoic acid (45 mg, 0.350 mmol), EDC^»HC1 (67 mg, 0.350 mmol), HOBt^»H₂0 (71 mg, 0.467 mmol) and DIPEA (60.2 mg, 0.467 mmol), and the reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with CH₂C1₂ and washed with water. The combined CH₂C1₂ layer was washed with brine, dried over anhydrous Na₂S0₄, and concentrated under reduced pressure. Purification by flash column chromatography (Si0₂, 100-200 mesh; 15% EtOAc in petroleum ether) afforded the title compound as a pale yellow liquid (30 mg, 35%): ^]H NMR (400 MHz, CDC1₃) δ 8.41 (s, 1H), 7.77 (s, 1H), 7.47 (br s, 1H), 7.40 (s, 2H), 6.58 (d, J = 16.0 Hz, 1H), 6.45 (dd, J = 16.0, 8.0 Hz, 1H), 4.68 (d, J = 4.0 Hz, 2H), 4.14 (m, 1H), 3.24 (q, J = 10.8 Hz, 2H); ESIMS m/z

536.88 ([M-H]^"); IR (thin film) 3320, 1674, 1114, 808.

Compound CC45 in Table 1 was made in accordance with the procedures disclosed in Example 83.

Example 84: Preparation of (£)-3,3,3-Trifluoro- V-((4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)naphthalen-l-yl)methyl)propanamide (CC46)

To a stirred solution of (£)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but- l-en- l- yl)naphthalen- l-yl)methanamine (0.1 g, 0.22 mmol) in CH₂C1₂ (8 mL) were added 3,3,3- trifluoropropanoic acid (0.032 g, 0.24 mmol), HOBf H₂0 (52 mg, 0.33 mmol), EDC'HCl (0.065 g, 0.33 mmol) and DIPEA (0.044 g, 0.45 mmol), and the resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and extracted with EtOAc (3 x30 mL). The combined EtOAc layer was washed with brine, dried over Na₂S0₄, and concentrated under reduced pressure. Purification by flash column chromatography (Si0₂, 100-200 mesh; 15% EtOAc in n-hexane) afforded the title compound as a gummy material (60 mg, 50%): mp 151-153 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.06 (m, IH), 7.61 (m, 4H), 7.48 (s, 2H), 7.44 (d, / = 8.0 Hz, IH), 7.38 (m, IH), 6.42 (m, IH), 5.92 (br s, IH), 4.92 (m, 2H), 4.24 (m, IH), 3.12 (m, 2H); ESIMS m/z 554.04 ([M-H]^").

Compounds CC47 - CC48 in Table 1 were made in accordance with the procedures disclosed in Example 84.

Example 85: Preparation of (£)-l-Ethyl-3-((4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en- -yl)naphthalen-l-yl)methyl)urea (CC49)

To a stirred solution of (£)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l- yl)naphthalen-l-yl)methanamine (0.1 g, 0.22 mmol) in CH₂CI₂ at 0 °C were added TEA (0.064 mL, 0.44 mmol) and ethylisocyanate (0.023 mL, 0.33 mmol), and the reaction mixture was stirred for 1 h at 0 °C. The reaction mixture was diluted with CH₂CI₂. The organic layer was washed with water and brine, dried over Na₂S0₄, and concentrated under reduced pressure. Purification by column chromatography (S1O2, 100-200 mesh; 30% EtOAc in hexane) afforded the title compound as a solid (0.07 g, 60%): mp 84-87 °C; ^]H NMR (400 MHz, CDCI₃) δ 8.06 (m, IH), 7.98 (m, IH), 7.61 (m, 3H), 7.48 (s, 2H), 7.44 (d, J = 8.0 Hz, IH), 7.38 (m, 2H), 6.42 (m, IH), 4.92 (s, 2H), 4.6 (br s, IH), 4.24 (m, IH), 3.21 (m, 2H), 1.2 (t, / = 4.6 Hz, 3H); ESIMS m/z 515.33 ([M+H]⁺).

Example 86: Preparation of (£)- V'-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l- en-l-yl)phenyl)cyclopropanecarbohydrazide (CC50)

To a stirred solution of (£)-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l- yl)phenyl)hydrazine (0.1 g, 0. 3 mmol) in CH₂C1₂ (10 mL) was added DIPEA (65 mg, 0.51 mmol), HOBfH₂0 (59 mg, 0.38 mmol), EDOHC1 (73 mg, 0.38 mmol) and

cyclopropanecarbonyl chloride (0.024 g, 0.28 mmol), and the reaction mixture was stirred at ambient temperature for 1 h. The reaction mixture was diluted with satd aq NaHCC>3 solution and extracted with (ϋΗ₂(¾. The combined CH₂CI₂ layer was washed with brine, dried over anhydrous Na₂S0₄, and concentrated under reduced pressure. Purification by flash column chromatography (S1O2; 5-25% EtOAc in petroleum ether) afforded the title compound as a solid (65 mg, 55%): mp 138-140 °C; ^]H NMR (400 MHz, CDC1₃) δ 9.81 (s, 1H), 7.90 (s, 1H), 7.84 (s, 2H), 7.34 (d, / = 8.4 Hz, 2H), 6.65 (d, / = 15.6 Hz, 1H), 6.61 (m, 1H), 6.57 (s, 1H), 6.48 (dd, / = 15.6, 8.8 Hz, 1H), 4.74 (m, 1H), 1.64 (m, 1H), 0.75 (m, 4H); ESIMS m/z 461.32 ([M-H] ).

Compound CC51 in Table 1 was made in accordance with the procedures disclosed in Example 86.

Example 87: Preparation of (£)- V-(4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en- l-yl)phenoxy)cycloprop

To a stirred solution of (£^')-0-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but- l-en-l-yl)phenyl)hydroxylamine (0.15 g, 0.38 mmol) in CH₂CI₂ (5 mL) was added EDC^»HC1 (0.109 g, 0.569 mmol), HOBfH₂0 (0.087 g, 0.569 mmol), DIPEA (0.097 g, 0.758 mmol) and cyclopropanecarboxylic acid (0.049 g, 0.569 mmol). The resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and extracted with CHCI₃ (35 mL) The combined CHCI₃ layer was washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure. Purification by flash column

chromatography (Si0₂; 20% EtOAc in hexane) afforded the title compound as a brown liquid (0.06 g, 34%): ^]H NMR (400 MHz, CDC1₃) δ 7.40 (s, 2H), 7.18 (s, 1H), 7.08 (s, 1H), 6.85 (m, 1H), 6.45 (m, 1H), 6.65 (m, 1H), 6.20 (m, 1H), 5.55 (s, 1H), 4.08 (m, 1H), 1.90 (m, 1H), 1.30 - 1.10 (m, 4H); ESIMS m/z 464.87 ([M-H]^").

Compound CC53 in Table 1 was made in accordance with the procedures disclosed in Example 87.

Example 88: Preparation of (Z)-3,3,3-Trifluoro- V-(4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en- -yl)benzyl)propanamide (CC54)

A silicon borate vial was charged with (E)-3,3,3-trifluoro-N-(4-(4,4,4-trifluoro-3- (3,4,5-trichlorophenyl)but-l-en-l-yl)benzyl)propanamide (133 mg, 0.269 mmol) and dimethyl sulfoxide (DMSO; 10 mL). The mixture was placed within 0.6 to 1 meter (m) of a bank of eight 115 watt Sylvania FR48T12/350BL/VHO/180 Fluorescent Tube Black Lights and four 115 watt Sylvania (daylight) F48T12/D/VHO Straight T12 Fluorescent Tube Lights for 72 h. The mixture was concentrated in vacuo and purified by reverse phase

chromatography to give the title compound as a colorless oil (11 mg, 8%): ^]H NMR (300 MHz, CDC1₃) δ 7.28 (s, 2H), 7.25 (m, 2H), 7.10 (d, / = 8.0 Hz, 2H), 6.89 (d, / = 11.4 Hz, 1H), 6.07 (br s, 1H), 6.01 (m, 1H), 4.51 (d, / = 5.8 Hz, 2H), 4.34 (m, 1H), 3.12 (q, 7 = 7.5 Hz, 2H); ¹³C NMR (101 MHz, CDC1₃) δ 162.44, 137.20, 135.38, 135.23, 134.82, 134.68, 131.71, 129.00, 128.80, 128.69, 128.10, 127.96, 122.63,76.70, 47.33 (q, / = 28 Hz), 43.59, 42.12 (q, / = 30 Hz); ESIMS m/z 504 ([M+H]⁺).

Compounds DC46, AC93. AC94 in Table 1 were made in accordance with the procedures disclosed in Example 88.

Example 89: Preparati -(l-Bromo-2,2,2-trifluoroethyl)-3-chlorobenzene (DI2)

The title compound was synthesized in two steps via l-(3-chlorophenyl)-2,2,2- trifluoroethanol (DIl, prepared as in Step 1, Method B in Example 1); isolated as a colorless viscous oil (1.5 g, 75%): ^]H NMR (400 MHz, CDC1₃) δ 7.50 (s, 1H), 7.42-7.35 (m, 3H), 5.02 (m, 1H), 2.65 (br s, 1H)) and Step 2 in Example 1 and isolated (0.14 g, 22%): ^]H NMR (400 MHz, CDCI₃) δ 7.50 (br s, 1H), 7,42-7.35 (m, 3H), 5.07 (m, 1H).

The following compounds were made in accordance with the procedures disclosed in Example 89.

(l-Bromo-2,2,2-trifluoroethyl)benzene (DI4)

DI3 DI4

2,2,2-Trifluoro-l-phenylethanol (DI3) was isolated (10 g, 80%): ^]H NMR (300 MHz, CDCI₃) δ 7.48 (m, 2H), 7.40 (m, 3H), 5.02 (m, 1H), 2.65 (d, / = 7.1 Hz, 1H). The title compound (DI4) was isolated as a liquid (8.0 g, 60%): ^]H NMR (400 MHz, CDC1₃) δ 7.50 (m, 2H), 7.40 (m, 3H), 5.00 (q, / = 7.5 Hz, 1H).

l-(l-Bromo-2,2,2-trifluoroethyl)-3,5-dimethylbenzene (DI20)

l-(3,5-Dimethylphenyl)-2,2,2-trifluoroethanol (DI19) was isolated an off white solid : ^]H NMR (400 MHz, CDC1₃) δ 7.05 (s, 2H), 7.02 (s, IH), 4.95 (m, IH), 2.32 (s, 6H); ESIMS m/z 204 ([M]^"). The title compound (DI20) was isolated (3.0 g, 51 ).

l-(l-Bromo-2,2,2-trifluoroethyl)-2,4-dichlorobenzene (DI22)

DI21 DI22

l-(2,4-Dichlorophenyl)-2,2,2-trifluoroethanol (DI21) was isolated as an off white powder (5.3 g, 61%): mp 49-51 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.62-7.66 (d, IH), 7.42- 7.44 (d, IH), 7.32-7.36 (d, IH), 5.6 (m, IH), 2.7 (s, IH); ESIMS m/z 244 ([M]⁺). The title compound (DI22) was isolated (3.2 g, 50%): ^]H NMR (400 MHz, CDC1₃) δ 7.62-7.72 (m, IH), 7.4-7.42 (m, IH), 7.3-7.38 (m, IH), 5.7-5.8 (m, IH).

l-(l-Bromo-2,2,2-trifluoroethyl)-2,3-dichlorobenzene (DI24)

l-(2,3-Dichlorophenyl)-2,2,2-trifluoroethanol (DI23) was isolated as a pale yellow oil

(5.2 g, 60%): ^]H NMR (400 MHz, CDC1₃) δ 7.62-7.64 (d, IH), 7.52-7.54 (m, IH), 7.29-7.33 (t, IH), 5.6-5.76 (m, IH), 2.7 (s, IH); ESIMS m/z 243.9 ([M]⁺). The title compound (DI24) was isolated as an oil (8.7 g, 60%): ^]H NMR (400 MHz, CDC1₃) δ 7.62-7.71 (m, IH), 7.44- 7.52 (m, IH), 7.27-7.3 (s, IH), 5.81-5.91 (m, IH).

2-(l-Bromo-2,2,2-trifluoroethyl)-l,4-dichlorobenzene (DI26)

l-(2,5-Dichlorophenyl)-2,2,2-trifluoroethanol (DI25) was isolated as a yellow oil (4.1 g, 60%): ^]H NMR (400 MHz, CDC1₃) δ 7.68-7.7 (s, IH), 7.3-7.37 (m, 2H), 5.51-5.6 (m, IH), 2.7 (s, IH); ESIMS m/z 244 ([M]⁺)). The title compound (DI26) was isolated (3.0 g, 60%): ^]H NMR (400 MHz, CDC1₃) δ 7.7-7.78 (m, IH), 7.3-7.4 (m, 2H), 5.7-5.8 (m, IH). l-(l-Bromo-2,2,2-trifluoroethyl)-3,5-bis(trifluoromethyl)benzene (DI28)

l-(3,5-Bis(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol (DI27) was isolated (3.8 g, 60%): ^]H NMR (400 MHz, CDC1₃) δ 7.98 (m, 3H), 5.25 (m, IH), 3.2 (br, IH); ESIMS m/z 312.2 ([M]⁺). The title compound (DI28) was prepared and carried on crude.

l-(l-Bromo-2,2,2-trifluoroethyl)-2,3,5-trichlorobenzene (DI30)

2,2,2-Trifluoro-l-(2,3,5-trichlorophenyl)ethanol (DI29) was isolated as a white solid (4.0 g, 60%): mp 113-115 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.62 (d, IH), 7.50 (d, IH), 5.60- 5.70 (m, IH), 2.75 (s, IH); ESIMS m/z 278.0 ([M⁺]). The title compound (DI30) was isolated (2.9 g, 60%): ^]H NMR (400 MHz, CDC1₃) δ 7.70 (d, IH), 7.50 (d, IH), 5.72-5.82 (m, IH).

l-(l-Bromo-2,2,2-trifluoroethyl)-3-chloro-5-(trifluoromethyl)benzene (DI32)

l-(3-Chloro-5-(trifluoromethyl)phenyl)-2,2,2-trifluoroethanol (DI31) was isolated as a pale yellow oil (2.0 g, 50%): ^]H NMR (400 MHz, CDC1₃) δ 7.51 (m, 3H), 5.08 (m, IH), 2.81 (s, IH); ESIMS m/z 278.1 ([M]⁺). The title compound (DI32) was isolated oil (2.0 g, 40%): ESIMS m/z 342 ([M]⁺). 5-(l-Bromo-2,2,2-trifluoroethyl)-l,3-dichloro-2-methoxybenzene (DI34)

l-(3,5-Dichloro-4-methoxyphenyl)-2,2,2-trifluoroethanol (DI33) was isolated as an off white solid (0.8 g, 60%); mp 92-95 °C: ^]H NMR (400 MHz, CDC1₃) δ 7.41 (s, 2H), 5.00 (m, IH), 3.89 (s, 3H), 2.64 (m, IH); ESIMS m/z 274 ([M]⁺). The title compound (DI34) was isolated as a colorless liquid (0.6 g, 57%).

Example 90: Preparation of l-(l-Bromo-2,2,2-trifluoroethyl)-3,5-difluorobenzene (DI36)

The title compound was synthesized in two steps via l-(3,5-difluorophenyl)-2,2,2- trifluoroethanol (DI35, prepared as in Step 1, Method A in Example 1 ; isolated as a colorless oil (0.2 g, 75%): ^]H NMR (400 MHz, CDC1₃) δ 7.05 (m, 2H), 6.88 (m, IH), 5.06 (m, IH), 2.66 (s, IH); ESIMS m/z 212 ([M]⁺) and Step 2 in Example 1 and isolated (3.2 g, 50%); ^]H NMR (400 MHz, CDC1₃) δ 7.05 (m, 2H), 6.86 (m, IH), 5.03 (q, J = 7.4 Hz, IH).

Example 90.

l-(l-Bromo-2,2,2-trifl roethyl)-4-chlorobenzene (DI38)

DI37 DI38

l-(4-Chlorophenyl)-2,2,2-trifluoroethanol (DI37) was isolated as a colorless oil (5.0 g, 99%): ^]H NMR (400 MHz, CDC1₃) δ 7.44-7.38 (m, 4H), 5.05 (m, IH), 2.55 (s, IH); ESIMS m/z 210 ([M]⁺). The title compound (DI38) was isolated (3.0 g, 46 %): ^]H NMR (400 MHz, CDCI₃) δ 7.45 (d, J = 8.2 Hz, 2H), 7.37 (d, J = 8.2 Hz, 2H), 5.10 (q, / = 7.2 Hz, IH). l-(l-Bromo-2,2,2-trifluoroethyl)-4-methoxybenzene (DI40)

DI39 DI40

2,2,2-Trifluoro-l-(4-methoxyphenyl)ethanol (DI39) was isolated as a pale yellow liquid: ^]H NMR (400 MHz, CDC1₃) δ 7.41 (d, J = 8.8 Hz, 2H), 6.95 (m, J = 8.8 Hz, 2H), 5.00 (m, IH), 3.82 (s, 3H), 2.44 (s, IH); ESIMS m/z 206.1 ([M]⁺). The title compound

(DI40) was isolated (3.8 g, 62%).

l-(l-Bromo-2,2,2-trifluoroeth l)-4-fluorobenzene (DI42)

DI41 DI42

2,2,2-Trifluoro-l-(4-fluorophenyl)ethanol (DI41) was isolated as a colorless oil (5 g, 99%): ^]H NMR (400 MHz, CDC1₃) δ 7.48-7.45 (m, 2H), 7.13-7.07 (m, 2H), 5.06 (m, IH), 2.53 (s, IH); ESIMS m/z 194 ([M]⁺). The title compound (DI42) was prepared and carried on as crude intermediate.

l-(l-Bromo-2,2,2-trifluoroethyl)-4-methylbenzene (DI44)

DI43 DI44

2,2,2-Trifluoro-l-(/?-tolyl)ethanol (DI43) was isolated as colorless oil (5.0 g, 99%): ^]H NMR (400 MHz, CDC1₃) δ 7.37 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 5.02 (m, IH), 2.46 (m, IH), 2.37 (s, 3H); ESIMS m/z 190 ([M]⁺). The title compound (DI44) was isolated (3.0 g, 45%).

l-(l-Bromo-2,2,2-trifluoroethyl)-3-fluorobenzene (DI46)

DI45 DI46 2,2,2-Trifluoro-l-(3-fluorophenyl)ethanol (DI45) was isolated as a colorless viscous oil (2.8 g, 93%): ^]H NMR (400 MHz, CDC1₃) δ 7.41 (m, IH), 7.25 (m, 2H), 7.14 (m, IH), 5.06 (m, IH), 2.60 (s, IH); ESIMS m/z 194 ([M]⁺). The title compound (DI46) was isolated (2.0 g, 61%).

l-(l-Bromo-2,2,2-trifl roethyl)-2-fluorobenzene (DI48)

DI47 DI48

2,2,2-Trifluoro-l-(2-fluorophenyl)ethanol (DI47) was isolated as a colorless oil (2.5 g, 99%): ^]H NMR (400 MHz, CDC1₃) δ 7.40 (m, IH), 7.43 (m,lH), 7.24 (m, IH), 7.13 (m, IH), 5.42 (m, IH), 2.65 (s, IH); ESIMS m/z 194 ([M]⁺). The title compound (DI48) was isolated (2.0 g, 61%): ^]H NMR (400 MHz, CDC1₃) δ 7.61 (m, IH), 7.40 (m, IH), 7.23 (m, IH), 7.10 (m, IH), 5.40 (m, IH); GCMS m/z 255 ([M-H]^").

Example 91: Preparation of 4-(lH-l,2,4-triazol-l-yl)benzaldehyde (DI5)

To a stirring solution of 4-fluorobenzaldehyde (10.0 g, 80.6 mmol) in DMF (150 were added K2CO₃ (13.3 g, 96.7 mmol) and 1,2,4- triazole (6.67 g, 96.7 mmol) and the resultant reaction mixture was stirred at 120 °C for 6 h. After completion of reaction (by TLC), the reaction mixture was diluted with water and extracted with EtOAc (3 xlOO mL). The combined EtOAc layer was washed with water and brine, dried over Na₂SC>4, and concentrated under reduced pressure to afford the title compound as a solid (9.0 g, 65%): mp 145-149 °C: ^]H NMR (400 MHz, CDC1₃) δ 10.08 (s, IH), 8.70 (s, IH), 8.16 (s, IH), 8.06 (d, J = 8.0 Hz, 2H), 7.92 (d, J = 8.0 Hz, 2H); ESIMS m/z 173.9 ([M+H]⁺).

The following compound was made in accordance with the procedures disclosed in Example 91.

5-Formyl-2-(lH-l,2,4-triazol-l-yl)benzonitrile (DI49)

The title compound was isolated (2.8 g, 60%); ^]H NMR (400 MHz, CDC1₃) δ 10.10 (s, IH), 8.98 (s, IH), 8.35 (s, IH), 8.30 (d, IH), 8.22 (s, IH), 8.07 (d, IH); IR (thin film) 3433, 3120, 1702, 1599, 1510 cm^"1.

2-Chloro-4-(lH-l,2,4-triazol-l-yl)benzaldehyde (DI50)

The title compound was isolated as an off white solid (3.0 g, 40%): mp 149-151 °C; ]H NMR (400 MHz, CDC1₃) δ 10.05 (s, IH), 8.74 (s, IH), 8.17 (s, IH), 8.10 (s, IH), 7.90 (m, 2H) ; ESIMS m/z 208.10 ([M+H]⁺).

5-Methyl-4-(lH-l,2,4-triazol-l-yl)benzaldehyde (DI51)

The title compound was isolated as a white solid (0.5 g, 74 %): mp 109-111 °C; ^]H NMR (400 MHz, D₆-DMSO ) δ 10.06 (s, IH), 9.00 (s, IH), 8.30 (s, IH), 7.99 (s, IH), 7.92 (d, / = 9.2 Hz, IH), 7.69 (d, / = 9.2 Hz, IH), 2.30 (s, 3H); ESIMS m/z 188.13 ([M+H]⁺). Example 92: Preparation of 5-Formyl-2-(3-nitro-lH-l,2,4-triazol-l-yl)benzonitrile (DI52)

To a stirring solution of 2-fluoro-5-formylbenzonitrile (0.5 g, 3.3 mmol) in DMF (25 mL) were added K2CO₃ (0.68 g, 4.95 mmol) and 3-nitro-l,2,4 triazole (0.45 g, 4.2 mmol) and the resultant reaction mixture was stirred at ambient temperature for 14 h. After completion of reaction (TLC), the reaction mixture was diluted with water and extracted with EtOAc. The combined EtOAc layer was washed with water and brine then dried over Na₂SC>4 and concentrated under reduced pressure to afforded the title compound as a pale yellow solid (0.36 g, 45%): mp 170-172 °C; ^]H NMR (300 MHz, DMSO-d₆) δ 10.12 (s, IH), 9.61 (s, IH), 8.69 (s, IH), 8.45 (d, / = 9.3 Hz, IH), 8.23 (d, / = 9.3 Hz, IH); ESIMS m/z 242.3 ([M-H]^"); IR (thin film) 2238, 1705, 1551, 1314 cm^"1. Example 93: Preparation of 4-(3-Methyl-lH-l,2,4-triazol-l-yl)benzaldehyde (DI53)

To a stirring solution of 4-fluorobenzaldehyde (5.0 g, 40.32 mmol) in DMF (50 mL), were added K₂C0₃ (3.34 g, 40.32 mmol) and 3-methyl-l,2,4-trizole (3.34 g, 40.32 mmol) and the resultant reaction mixture was stirred at ambient temperature for 4 h. After completion of the reaction (TLC), the reaction mixture was diluted with water and extracted with EtOAc (3x). The combined EtOAc layer was washed with water and brine then dried over Na₂S0₄ and concentrated under reduced pressure to afforded the title compound as a white solid (4.1 g, 60%): mp 125-128°C; ^]H NMR (400 MHz, CDC1₃) δ 10.05 (s, 1H), 8.76 (s, 1H), 8.02 (d, 2H), 7.85 (d, 2H), 2.50 (s, 3H); ESIMS m/z 188.04 ([M+H]⁺).

The following compound was made in accordance with the procedures disclosed in Example 93.

4-(lH-l,2,4-triazol-l-yl)-3-(trifluoromethyl)benzaldehyde (DI54)

The title compound was isolated as white solid (1.05 g, 60%): mp 81-83 °C; Ή NMR

(400 MHz, CDCI₃) δ 10.15 (s, 1H), 8.43 (s, 1H), 8.37 (s, 1H), 8.25 (d, / = 7.2 Hz, 1H), 8.18 (s, 1H), 7.79 (d, / = 7.2 Hz, 1H); ESIMS m/z 241.0 ([M]⁺).

4-(3-Nitro-lH-l,2,4-triazol-l-yl)benzaldehyde (DI55)

The title compound was isolated as pale yellow solid (0.10 g, 23%): mp 159-161 °C; Η NMR (400 MHz, CDC1₃) δ 10.10 (s, 1H), 8.89 (s, 1H), 8.15 (m, 2H), 8.00 (m, 2H);

ESIMS m/z 217.11 ([M-H]^").

3-Bromo-4-(lH-l,2,4-triazol-l-yl)benzaldehyde (DI56)

The title compound was isolated as white solid (3.2 g, 51%): mp 126-128 °C; ^]H NMR (400 MHz, CDC1₃) δ 10.04 (s, IH), 8.69 (s, IH), 8.27 (M, IH, 8.18 (s, IH) 7.99 (d, / = 9.2 Hz, IH), 7.76 (d, J = 9.2 Hz, IH); ESIMS m/z 250.9 ([M]⁺).

5-Formyl-2-(3-methyl-lH-l,2,4-triazol-l-yl)benzonitrile (DI57)

The title compound was isolated as white solid (0.13 g, 30%): mp 147-149 °C; ^]H NMR (400 MHz, CDC1₃) δ 10.07 (s, IH), 8.89 (s, IH), 8.32 (d, / = 1.8 Hz, IH), 8.24 (dd, J 8.6, 1.3 Hz, IH), 8.06 (d, / = 8.6 Hz, IH), 2.54 (s, 3H); ESIMS m/z 213.09 ([M+H]⁺); IR (thin film) 2239, 1697 cm^"1.

3-Nitro-4-(lH-l,2,4-triazol-l-yl)benzaldehyde (DI58)

The title compound was isolated as pale yellow solid (3.0 g, 60 %): mp 116-118 °C; ^]H NMR (400 MHz, CDC1₃) δ 10.15 (s, IH), 8.48 (s, IH), 8.46 (s, IH), 8.26 (d, / = 6.9 Hz, IH), 8.16 (s, IH), 7.83 (d, J = 6.9 Hz, IH); ESIMS m/z 219.00 ([M+H]⁺).

Example 94: Preparation of l-(4-Vinylphenyl)-lH-l,2,4-triazole (DI59)

To a stirred solution of 4-[l,2,4]triazol-l-yl-benzaldehyde (9.0 g, 52 mmol) in 1,4- dioxane (100 rriL), were added K2CO₃ (10.76 g, 78 mmol) and methyl triphenyl phosphonium bromide (22.2 g, 62.4 mmol) at ambient temperature. The resultant reaction mixture was heated to 70 °C for 18 h. After completion of the reaction (TLC), the reaction mixture was cooled to ambient temperature and filtered and the obtained filtrate was concentrated under reduced pressure. Purification by flash chromatography (Si0₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) to afforded the title compound as a white solid (5.6 g, 63%): ESIMS m/z 172.09 ([M+H]⁺).

The following compound was made in accordance with the procedures disclosed in Example 94.

l-(2-Methyl-4-vinylphenyl)-lH-l,2, -triazole (DI60)

The title compound was isolated as an off white solid (1.5 g, 76%): ^]H NMR (400

MHz, CDC1₃) δ 8.25 (s, 1H), 8.11 (s, 1H), 7.35 (m, 2H), 7.27 (d, / = 8.7 Hz, 1H), 6.74 (m, 1H), 5.82 (d, / = 17.3 Hz, 1H), 5.36 (d, / = 10.0 Hz, 1H), 2.25 (s, 3H); ESIMS m/z 186.14 «M+H]⁺).

2-(lH-l,2,4-Triazol-l-yl)-5-vinylbe

The title compound was isolated as an off-white solid (1.40 g, 71%): mp 126-129 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.76 (s, 1H), 8.18 (s, 1H), 7.82-7.84 (m, 1H), 7.72-7.80 (m, 2H), 6.70-6.80 (dd, J = 17.6, 10.8 Hz, 1H), 5.90-5.95 (d, J = 17.6 Hz, 1H), 5.50-5.70 (d, J = 10.8 Hz, 1H); ESIMS m/z 197.03 ([M+H]⁺).

Example 95: Preparation of 2-(3-Nitro-lH-l 2 4-triazol-l-yl)-5-vinylbenzonitrile (DI62)

To a stirred solution of 5-formyl-2-(3-nitro-lH-l,2,4-triazol-l-yl)benzonitrile (0.36 g, 1.49 mmol) in 1,4-dioxane (25 mL), were added K₂CO₃ (0.3 g, 2.2 mmol) and methyl triphenyl phosphonium bromide (0.63 g, 1.79 mmol). The resultant reaction mixture was heated to 100 °C for 18 h. After completion of the reaction (TLC), the reaction mixture was cooled to ambient temperature and filtered and the obtained filtrate was concentrated under reduced pressure. Purification by flash chromatography (Si0₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) to afford the title compound as a solid (0.25 g, 70%): mp 103-105 °C; ^]H NMR (400 MHz, DMSO-d₆) δ 9.50 (s, 1H), 8.34 (m, 1H), 7.98 (d, / = 7.8 Hz, 1H), 7.68 (d, J = 7.8 Hz, 1H), 6.87 (m, 1H), 6.20 (d, J = 15.1 Hz, 1H), 5.56 (d, J = 11.8 Hz, 1H); ESIMS m/z 240.27 ([M-H]^"); IR (thin film) 2240, 1514, 1312 cm^"1.

The following compound was made in accordance with the procedures disclosed in Example 95.

l-(3-Chloro-4-vinylphenyl)-lH-l,2, -triazole (DI63)

The title compound was isolated as an off-white solid (2.3 g, 80%): mp 134-137 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.56 (s, 1H), 8.11 (s, 1H), 7.76 (s, 1H), 7.70 (d, / = 9.0 Hz, 1H), 7.57 (d, J = 9.0 Hz, 1H), 7.10 (m, 1H), 5.80 (d, J = 17.2 Hz, 1H), 5.47 (d, J = 12.4 Hz, 1H); ESIMS m/z 206.04 ([M+H]⁺.

3-Methyl-l-(4-vinylphenyl)-lH-l,2, -triazole (DI64)

The title compound was isolated as a white solid (0.6 g, 60%): mp 109-111 °C; ^]H

NMR (400 MHz, CDC1₃) δ 8.42 (s, 1H), 7.40-7.60 (m, 4H), 6.70-7.00 (dd, / = 17.6, 10.8 Hz, 1H), 5.80 (d, / = 17.6 Hz, 1H), 5.30 (d, / = 17.6 Ηζ,ΙΗ), 2.50 (s, 3H); ESIMS m/z 186.20 «M+H]⁺).

l-(2-(Trifluoromethyl)-4-vinylphen -lH-l,2,4-triazole (DI65)

The title compound was isolated as a colorless oil (0.6 g, 60%): ^]H NMR (400 MHz,

CDCI₃) δ 8.32 (s, 1H), 8.14 (s, 1H), 7.84 (s, 1H), 7.72 (d, / = 8.0 Hz, 1H), 7.50 (d, / = 7.6 Hz, 1H), 6.70-6.90 (dd, / = 17.6, 10.8 Hz, 1H), 5.90-6.00 (d, / = 17.6 Hz, 1H), 5.50-5.80 (d, / = 10.8 Hz 1H); ESIMS m/z 240.16 ([M+H]⁺).

3-Nitro-l-(4-vinylphenyl)-lH-l,2

The title compound was isolated as a pale yellow solid (61 mg, 20%): mp 137-139 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.60 (s, IH), 7.68 (d, J = 7.7 Hz, 2H),7.60 (d, J = 8.3 Hz, 2H), 6.77 (dd, J = 17.7, 10.8, IH), 5.87 (d, J = 17.7 Hz, IH), 5.42 (d, J = 10.8 Hz, IH); ESIMS m/z 217.28 ([M+H]⁺).

l-(2-Bromo-4-vinylphenyl)-lH-l,2, -triazole (DI67)

The title compound was isolated as a white solid (1.2 g, 40%): mp 75-77 °C; ^]H NMR (400 MHz, CDCI₃) δ 8.48 (s, IH), 8.12 (s, IH), 7.75 (s, IH) 7.42 (s, 2H), 6.70 (m, IH), 5.83 (d, / = 18 Hz, IH), 5.42 (d, / = 12 Hz, IH); ESIMS m/z 249.1 ([M]⁺).

2-(3-Methyl-lH-l,2,4-triazol-l-yl)- -vinylbenzonitrile (DI68)

The title compound was isolated as an off-white solid (0.6 g, 60%): mp 96-97 °C; ^]H

NMR (400 MHz, CDC1₃) δ 8.66 (s, IH), 7.80 (s, IH), 7.74 (m, 2H), 6.73 (dd, / = 17.6 I

10.8 Hz, IH), 5.88 (d, / = 17.6 Hz, IH), 5.49 (d, / = 10.8 Hz, IH), 2.52 (s, 3H); ESIMS 211.10 ([M+H]⁺); IR (thin film) 2229 cm^"1.

l-(2-Nitro-4-vinylphenyl)-lH-l,2,4

The title compound was isolated as a yellow solid (1.78 g, 60%): mp 102-104 °C; ^]H

NMR (400 MHz, CDC1₃) δ 8.40 (s, IH), 8.12 (s, IH), 8.02 (s, IH), 7.72-7.76 (d, / = 8.0 Hz, IH), 7.52-7.56 (d, / = 17.6 Hz, IH), 6.70-6.82 (dd, / = 17.6, 10.8 Hz, IH), 5.85-6.00 (d, / = 17.6 Hz, IH), 5.50-5.60 (d, / = 10.8, Hz IH); ESIMS m/z 217.0 ([M+H]⁺).

Example 96: Preparation of 3-Methyl-2-(lH-l,2,4-triazol-l-yl)-5-vinylbenzonitrile

(DI70) Step 1. 5-Bromo-2-fluoro-3-methylbenzaldehyde: To a stirred solution of di- isopropyl amine (4.01 g, 39.88 mmol) in THF (20 mL) was added n-butyl lithium (1.6 M in hexane) (19.9 mL, 31.91 mmol) at -78 °C slowly dropwise over the period of 10 min, the reaction mixture was stirred at -78°C for 30 min. A solution of 4-bromo-l-fluoro-2- methylbenzene (5.0 g, 26.6 mmol) in THF (30.0 mL) was added at -78°C, and the reaction mixture was stirred for lh at the same temperature. DMF (5.0 mL) was added and stirred at - 78°C for another 30 min. The reaction was monitored by TLC; then the reaction mixture was quenched with IN HC1 solution (aq) at 0°C. The aqueous layer was extracted with diethyl ether, washed with water and saturated brine solution. The combined organic layer was dried over anhydrous Na₂S0₄ and concentrated under reduced pressure to obtain the crude compound purified by flash column chromatography (Si0₂, 100-200 mesh; eluting with 5% ethyl acetate/ pet ether) to afford the title compound as a white solid (3.6 g, 64 ); mp 48- 50°C: ^]H NMR (400 MHz, CDC1₃) δ 8.33 (s, 1H), 8.22 (s, 1H), 7.67 (s, 1H), 7.60 (s, 1H), 6.75 (dd, J = 17.6, 10.8 Hz, 1H), 5.92 (dd, J = 17.6, 10.8 Hz, 1H), 5.52 (d, J = 17.6 Hz, 1H), 2.21 (s, 3H); ESIMS m/z 211.35 ([M-H]^").

Step 2. ((£')-5-Bromo-2-fluoro-3-methylbenzaldehyde oxime: To a stirred solution of 5-bromo-2-fluoro-3-methylbenzaldehyde (3.5 g, 16.2 mmol) in ethanol (50.0 mL) were added sodium acetate (2.0 g, 24.3 mmol) and hydroxylamine hydrochloride (1.69 g, 24.3 mmol) at ambient temperature. The reaction mixture was stirred at ambient temperature for 3 h. The reaction mixture was concentrated on rotavapour to obtain crude compound, which was washed with water filtered and dried under vacuum to afford the title compound as a white solid: mp 126-127 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.32 (s, 1H), 7.73 (d, J = 2.4 Hz, 1H), 7.51 (s, 1H), 7.34 (d, J = 2.4 Hz, 1H), 2.25 (s, 3H); ESIMS m/z 232.10 ([M+H]⁺).

Step 3. 5-Bromo-2-fluoro-3-methylbenzonitrile: A stirred solution of (£)-5-bromo- 2-fluoro-3-methylbenzaldehyde oxime (0.5 g, 2.2 mmol) in acetic anhydride (5.0 mL) was heated to reflux for 18 h. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined ethyl acetate layer was washed with brine and dried over Na₂S0₄ and concentrated under reduced pressure to afford the crude compound as a light brown gummy material (0.4 g, crude): ESIMS m/z 213.82 ([M+H]⁺).

Step 4. 5-Bromo-3-methyl-2-(lH-l,2,4-triazol-l-yl)benzonitrile (DI71) : To a stirred solution of 5-bromo-2-fluoro-3-methylbenzonitrile (1.0 g, 47.716 mmol), in DMF (10.0 mL) was added potassium carbonate (1.95 g, 14.14 mmol) followed by 1H-1,2,4- triazole (0.811 g, 9.433 mmol) at ambient temperature. The reaction mixture was heated to 140 °C for 18 h. The reaction mixture was cooled to ambient temperature, diluted with water and extracted with ethyl acetate (2 x 100 mL). The combined ethyl acetate layer was washed with brine and dried over Na₂S0₄ and concentrated under reduced pressure to afford the crude compound purified by flash column chromatography (Si0₂, 100-200 mesh; eluting with 30% ethyl acetate/ pet ether) to afford the title compound as a pink solid (0.6 g, 49 %): ^]H NMR (400 MHz, CDC1₃) δ 8.39 (s, IH), 8.23 (s, IH), 7.91 (d, / = 2.4 Hz, 2H), 2.21 (s, 3H), ESIMS m/z 262.57 ([M+H]⁺); IR (thin film) 2231, 554 cm^"1.

Step 5. 3-Methyl-2-(lH-l,2,4-triazol-l-yl)-5-vinylbenzonitrile (DI70) : A mixture of 5-bromo-3-methyl-2-(lH-l,2,4-triazol-l-yl)benzonitrile (0.6 g, 2.3 mmol), potassium carbonate (0.95 g, 6.87 mmol), vinyl boronic anhydride (0.82 g, 3.43 mmol) and

triphenylphosphine (0.13 g, 0.114 mmol) in toluene (20.0 mL) were stirred and degassed with argon for 30 min. The reaction mixture was heated to reflux for 18 h. The reaction mixture was cooled to ambient temperature, diluted with water and extracted with ethyl acetate (2 x 100 mL). The combined ethyl acetate layer was washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure to afford the crude compound that was purified by flash column chromatography (Si0₂, 100-200 mesh; eluting with 30% ethyl acetate/ pet ether) to afford the title compound as a pink solid (0.25 g, 52 %): ^]H NMR (400 MHz, CDC1₃) δ 8.33 (s, IH), 8.22 (s, IH), 7.67 (s, IH), 7.60 (s, IH), 6.75 (dd, / = 17.6, 10.8 Hz, IH), 5.92 (d, / = 17.6, IH), 5.52 (d, / = 10.8 Hz, IH), 2.21 (s, 3H), ESIMS m/z 211.35 ([M+H]⁺); IR (thin film) 2236, 1511 cm^"1.

The following compound was made in accordance with the procedures disclosed in

Steps 4 and 5 of Example 96.

l-(2-Fluoro-4-vinylphenyl)-lH-l,2, -triazole (DI72)

l-(4-Bromo-2-fluorophenyl)-lH-l,2,4-triazole (DI73) was isolated as a pale yellow solid (3.0 g, 75%): mp 113-116 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.69 (s, IH), 8.13 (m,

2H), 7.50 (m, IH), 7.21 (m, IH); ESIMS m/z 241.93 ([M]⁺). The title compound (DI72) was isolated as a yellow solid (1.0 g, 71%): mp 67-70 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.67 (s, IH), 8.13 (s, IH), 7.94 (m, IH), 7.41 (m, IH), 7.24 (s, IH), 6.75 (dd, J = 17.6, 10.8 Hz, IH ), 5.81 (d, / = 17.6 Hz, IH), 5.37 (d, / = 10.8 Hz, IH); ESIMS m/z 190.00 ([M+H]⁺).

Example 119: Preparation of l-(l-(4-Vinylphenyl)-lH-l,2,4-triazol-5-yl)ethanone (DI78)

To a stirred solution of l-(4-vinyl-phenyl)-lH-[l,2,4]triazole (1 g, 5.8 mmol) in 25 mL of THF, was added n-BuLi (0.37 g, 5.8 mmol) at -78 °C and stirred for 30 min. To this N- methoxy-N-methyl acetamide in THF (0.66 g, 6.4 mmol) was added and the resultant reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was quenched with a saturated aqueous NH₄C1 solution and extracted with EtOAc (3 x50 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure. The crude compound was purified by flash chromatography (Si0₂, 100-200 mesh, 40% EtOAc in Pet ether) to afford the title compound as an off white solid (280 mg, 23%): mp 97-98 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.10 (s, 1H), 7.50 (d, 2H), 7.38 (d, 2H), 6.68 (dd, 1H), 5.85 (d, 1H), 5.38 (d, 1H), 2.75 (s, 3H); ESIMS m/z 214.14 ([M+H]⁺).

Example 120: Preparation of Cyclopropyl(l-(4-vinylphenyl)-lH-l,2,4-triazol-5- yl)methanone (DI79)

To a stirred solution of l-(4-vinyl-phenyl)-lH-[l,2,4]triazole (1 g, 5.8 mmol) in 25 mL of THF, was added n-BuLi (0.37 g, 5.8 mmol) at -78 °C and stirred for 30 min. To this N- methoxy N-methylcyclopropoxide in THF (0.82 g, 6.4 mmol) was added and the resultant reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was quenched with a saturated aqueous NH₄CI solution and extracted with EtOAc (3 x25 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure. The crude compound was purified by flash

chromatography (Si0₂, 100-200 mesh, 40% EtOAc in Pet ether) to afford the title compound as an off white solid (420 mg, 30%): mp 90-91 °C; ^]H NMR (400 MHz, CDC1₃) δ 8.12 (s, 1H), 7.50 (d, J = 7.8 Hz, 2H), 7.38 (d, J = 7.8 Hz, 2H), 6.75 (dd, J = 16.3, 10.7 Hz, 1H), 5.81 (d, / = 16.3 Hz, 1H), 5.35 (d, / = 10.7 Hz, 1H), 3.22 (m, 1H), 1.27(m, 2H), 1.18 (m, 2H); ESIMS m/z 240.18 ([M+H]⁺); IR (thin film) 2922, 1630 cm^"1.

Example 121: Preparation of 5-(Methylthio)-l-(4-vinylphenyl)-lH-l,2,4-triazole (DI80) To a stirred solution of l-(4-vinyl-phenyl)-lH-[l ,2,4]triazole (1 g, 5.8 mmol) in 50 mL of THF, was added n-BuLi (0.41 g, 6.4 mmol) at -78 °C and stirred for 30 min. To this dimethyldisulfide in THF (0.6 g, 6.43 mmol) was added and the resultant reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was quenched with a saturated aqueous NH₄C1 solution and extracted with EtOAc (3 x 25 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure. The crude compound was purified by flash chromatography (Si0₂, 100-200 mesh, 40% EtOAc in Pet ether) to afford the title compound as an off white solid (0.6 g, 48%): mp 68-70 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.96 (s, 1H), 7.05 (m, 4H), 6.75 (dd, / = 16.4, 10.7 Hz, 1H), 5.81 (d, J = 16.4 Hz, 1H), 5.35 (d, J = 10.7 Hz, 1H), 2.73 (s, 3H); ESIMS m/z 218.09 ([M+H]⁺).

Example 122: Preparation of 5-Methyl-l-(4-vinylphenyl)-lH-l,2,4-triazole (DI81)

To a stirred solution of l-(4-vinyl-phenyl)-lH-[l ,2,4]triazole (0.5 g, 2.9 mmol) in 10 mL of THF, was added n-BuLi (0.22 g, 3.5 mmol) at -78 °C and stirred for 30 min. To this methyl iodide in THF (0.50 g, 3.5 mmol) was added and the resultant reaction mixture was stirred at ambient temperature for 16 h. The reaction mixture was quenched with a saturated aqueous NH₄C1 solution and extracted with EtOAc (3 x 25 mL). The combined EtOAc layer was washed with brine and dried over sodium sulphate and concentrated under reduced pressure The crude compound was purified by flash chromatography (Si0₂, 100-200 mesh, 40% EtOAc in Pet ether) afford the title compound as a pale brown liquid (250 mg, 46%): ^]H NMR (400 MHz, CDC1₃) δ 7.93 (s, 1H), 7.55 (d, / = 9 Hz, 2H), 7.42 (d, / = 9 Hz, 2H), 6.76 (dd, / = 18, 11 Hz, 1H), 5.83 (d, / = 18 Hz, 1H), 5.38 (d, / = 11 Hz, 1H), 2.55 (s, 3H); ESIMS m/z 186.13 ([M+H]⁺); IR (thin film) 1517, 1386, 1182, 847 cm^"1.

Example 97: Preparation of (E)-l-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-en-l- yl)phenyl)-lH-l,2,4-triazole (DC1)

To a stirred solution of l-(l-bromo-2,2,2-trifluoro-ethyl)-3,5-dichloro-benzene (2.0 g, 6.51 mmol) in 1,2-dichlorobenzene (25 mL), were added l-(4-vinyl-phenyl)- lH- [l,2,4]triazole (2.22 g, 13.0 mmol), CuCl (64 mg, 0.65 mmol) and 2,2 -bipyridyl (0.2 g, 1.3 mmol). The resultant reaction mixture was degassed with argon for 30 min, then stirred at 180 °C for 24 h. After completion of reaction (TLC), the reaction mixture was cooled to ambient temperature and filtered and the filtrate concentrated under reduced pressure.

Purification by flash chromatography (Si0₂, 100-200 mesh; 25-30% EtOAc in petroleum ether) afforded the title compound as an off-white solid (0.8 g, 32%): mp 93-97 °C; ^]H NMR (300 MHz, CDC1₃) δ 8.56 (s, 1H), 8.11 (s, 1H), 7.68 (d, / = 8.4 Hz, 2H), 7.54 (d, / = 8.4 Hz, 2H), 7.38 (t, J = 1.8 Hz, 1H), 7.29 (s, 2H), 6.62 (d, J = 15.6 Hz, 1H), 6.42 (dd, J = 15.6, 8.2 Hz, 1H), 4.15 (m, 1H); ESIMS m/z 398.05 ([M+H]⁺).

Compounds DC2-DC37, DC44, DC45, DC47-49, DC50, DC51, DC54, DC58,

DC60, DC62, and DC63-DC67 in Table 1 were made in accordance with the procedures disclosed in Example 97.

Example 98: Preparation of (E)-2-(3-Nitro-lH-l,2,4-triazol-l-yl)-5-(4,4,4-trifluoro-3- (3,4,5-trichlorophenyl)bu -l-en-l-yl)benzonitrile (DC40)

To a stirred solution of 2-(3-nitro-lH-l,2,4-triazol-l-yl)-5-vinylbenzonitrile (0.9 g, 3.7 mmol) in 1,2- dichlorobenzene (10 mL), were added 5-(l-bromo-2,2,2-trifluoroethyl)- 1,2,3-trichlorobenzene (2.5 g, 7.5 mmol), CuCl (73 mg, 0.74 mmol) and 2,2-bipyridyl (0.23 g, 1.49 mmol) and the resultant reaction mixture was degassed with argon for 30 min and then stirred at 180°C for 14 h. After completion of the reaction (TLC), the reaction mixture was cooled to ambient temperature and filtered and the filtrate was concentrated under reduced pressure. Purification by flash chromatography (Si0₂, 100-200 mesh, 25-30% EtOAc in Pet ether) afforded the title compound as an off white solid (0.9 g, 50%): mp 70-73 °C; ^]H NMR (300 MHz, CDC1₃) δ 8.86 (s, 1H), 7.88 (m, 3H), 7.44 (s, 2H), 6.67 (d, / = 16.0 Hz, 1H), 6.56 (dd, / = 16.0, 7.6 Hz, 1H), 4.19 (m, 1H); ESIMS m/z 436.11 ([M-2H]^").

Example 99: Preparation of (E)-2-(3-Amino-lH-l,2,4-triazol-l-yl)-5-(4,4,4-trifluoro-3- (3,4,5-trichlorophenyl)bu - 1 -en-1 -yl)benzonitrile (DC41)

To a stirred solution of (E)-2-(3-nitro-lH-l,2,4-triazol-l-yl)-5-(4,4,4-trifluoro-3- (3,4,5-trichlorophenyl)but-l-enyl)benzonitrile (0.6 g, 1.2 mmol) in MeOH (10 mL), were added Zn dust (0.39g, 5.98 mmol) and sat. aq NH₄C1 solution (5 mL) and the resultant reaction mixture was stirred at ambient temperature for 2 h. After completion of the reaction (TLC), the reaction mass was concentrated under reduced pressure. The reaction mass was diluted with CH₂CI₂, filtered through a celite bed, and the obtained filtrate concentrated under reduced pressure to afford the title compound as a solid (0.5 g, 89%): mp 72-75 °C; ^]H NMR (300 MHz, DMSO-d₆) δ 8.72 (s, 1H), 8.26 (s, 1H), 8.01 (d, / = 8.4 Hz, 1H), 7.91 (s, 2H), 7.77 (d, J = 8.4 Hz, 1H), 6.42 (dd, J = 15.6, 9.2 Hz, 1H), 6.83 (d, J = 15.6 Hz, 1H), 5.87 (s, 2H), 4.89 (m, 1H); ESIMS m/z 469.95 ([M-H]^").

Compound DC38 in Table 1 was made in accordance with the procedures disclosed in Example 99. Also, compound DC55 in Table 1 was made from compound DC54 in accordance with the procedures disclosed in Example 99, with the exception of using ammonium formate in place of ammonium chloride.

Example 100: Preparation of (E)- V-(l-(2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)phenyl)-lH-l,2,4-triazol-3-yl)-N- (cyclopropanecarbonyl)cyclopropanecarboxamide (DC42)

To a stirred solution of (E)-2-(3-amino-lH-l,2,4-triazol-l-yl)-5-(4,4,4-trifluoro-3-

(3,4,5-trichlorophenyl)but-l-enyl)benzonitrile (0.1 g, 0.21 mmol) in CH₂CI₂ at ambient temperature, was added cyclopropylcarbonyl chloride (0.045 g, 0.42 mmol) and the reaction mixture was stirred for 2 h at ambient temperature. The reaction mixture was diluted with CH₂CI₂ and washed with water and brine and dried over Na₂S0₄. Concentration under reduced pressure and purification by preparative HPLC afforded the title compound as a solid

(0.09g, 79%): mp 104-107 °C; ^]H NMR (300 MHz, CDC1₃) δ 8.78 (s, 2H), 7.83 (s, 1H), 7.80 (m, 2H), 7.42 (s, 2H) , 6.65 (d, / = 16.4 Hz, 1H), 6.51 (dd, / = 7.6, 8.0 Hz, 1H), 4.17 (m, 1H), 2.16 (m, 2H), 1.25 (m, 4H), 1.00 (m, 4H); ESIMS m/z 609.98 ([M+H]⁺); IR (thin film) 2234, 1714, 1114, 807 cm^"1. Example 101: Preparation of (E)- V-(l-(2-Cyano-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)phenyl)-lH-l,2,4-triazol-3-yl)cyclopropanecarboxamide

(DC43)

To a stirred solution of (E)-2-(3-amino-lH-l,2,4-triazol-l-yl)-5-(4,4,4-trifluoro-3- (3,4,5-trichlorophenyl)but-l-enyl)benzonitrile (0.15 g,0.31 mmol) in CH₂CI₂ at 0 °C, were added TEA (0.1 g, 1 mmol) and cyclopropylcarbonyl chloride (0.04 g, 0.38mmol) and the reaction mixture was stirred for 1 h at 0 °C. The reaction mixture was diluted with CH₂C1₂ and washed with water and brine and dried over Na₂S0₄. Concentration under reduced pressure and purification by column chromatography (Si0₂, 100-200 mesh) afforded the title compound as a solid (66 mg, 34%): mp 109-112 °C; ^]H NMR (300 MHz, DMSO- ) δ 10.94 (br s, 1H), 8.36 (s, 1H), 8.08 (m, 7 = 8.4 Hz, 1H), 7.91 (s, 2H), 7.84 (d, 7 = 8.4 Hz, 1H), 7.13 (dd, 7 = 15.6, 9.2 Hz, 1H), 6.87 (d, 7 = 15.6 Hz, 1H), 4.92 (m, 1H), 1.99 (br s, 1H), 0.82 (s, 4H); ESIMS m/z 540.04 ([M+H]⁺); IR (thin film) 3233, 2233, 1699, 1114, 807cm^"1.

Compound DC39 in Table 1 was made in accordance with the procedures disclosed in Example 101.

Example 102: Preparation of l-(4-(lH-l,2,4-triazol-l-yl)phenyl)ethanone (DI74)

To a stirred solution of 4-bromoacetophenone (10 g, 50 mmol) in DMF (100 mL), were added 1,2,4-triazole (5 g, 75mmol), Cs₂C0₃ (32.6 g, 100.5 mmol) and Cul (1.4 g, 10.1 mmol) and the resultant reaction mixture was refluxed for 48 h. After completion of the reaction (by TLC), the reaction mixture was cooled to ambient temperature and diluted with water (200 mL) and extracted with EtOAc. The combined organic layer was washed with brine and dried over Na₂S0₄ and concentrated under reduced pressure. Purification by washing with diethyl ether afforded the title compound as a solid (5 g, 96%): ^]H NMR (400

MHz, CDCI₃) δ 8.71 (s, 1H), 8.16, (s, 1H), 8.13 (d, 7 = 8.6 Hz, 2H), 7.83 (d, 7 = 8.6 Hz, 2H), 2.66 (s, 3H); ESIMS m/z 186.02 ([M-H]^"). Example 103: Preparation of l-(4-(lH-l,2,4-triazol-l-yl)phenyl)-3-(3,5-dichlorophenyl)- 4,4,4-trifluorobutan-l-one (DI75)

Step 1. l-(4-(l-(Trimethylsilyloxy)vinyl)phenyl)-lH-l,2,4-triazole (DI76) To a stirred solution of l-(4-(lH-l,2,4-triazol-l-yl)phenyl)ethanone (4.5 g, 24.0 mmol) in CH₂C1₂ at 0 °C, were added TEA (3.7 g, 36.1 mmol) and trimethylsilyl triflluoromethanesulfonate (8 g, 36 mmol) and the resultant reaction mixture was stirred for 1 h. The reaction mixture was quenched with a mixture of sat aq sodium bicarbonate solution and ether. The ether layer and was separated, washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure to afford the title compound (5.5 g) which was taken directly to next step.

Step 2. l-(4-(lH-l,2,4-triazol-l-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4- trifluorobutan-l-one (DI75): To a stirred solution of l-(4-(l-

(trimethylsilyloxy)vinyl)phenyl)-lH-l,2,4-triazole (6g, 23 mmol) and l-(l-bromo-2,2,2- trifluoro-ethyl)-3,5-dichlorobenzene (7.1 g, 34.7 mmol) in 1 ,2-dichlorobenzene (30 mL) was degassed with argon. To this CuCl (0.23g, 2.31 mmol) and 2,2-bipyridyl (0.73g, 4.63 mmol) was added to the above reaction mixture and the resultant reaction mixture was heated to 180 °C for 18 h. After completion of the reaction (by TLC), the reaction mixture was absorbed onto silica gel and purified by column chromatography (Si02; 10% EtOAc in petroleum ether) to afford title compound as a solid (3 g, 31 %): ^]H NMR (400 MHz, CDC1₃) δ 8.67 (s, 1H), 8.15 (s, 1H), 8.10 (d, / = 8.3 Hz, 2H), 7.82 (d, 7 = 8.3 Hz, 2H), 7.33 (m, 1H), 7.30 (m, 2H), 4.20 (m, 1H), 3.63 (m, 2H); ESIMS m/z 412. 14 ([M-H]^").

Example 104: Preparation of 2-(4-(lH-l,2,4-triazol-l-yl)phenyl)-4-(3,5-dichlorophenyl)- 5,5,5-trifluoropentan-2-ol (D

To a solution of l-(4-(lH-l,2,4-triazol-l-yl)phenyl)-3-(3,5-dichlorophenyl)-4,4,4- trifluorobutan-l-one (300 mg, 0.726 mmol ) in THF cooled to 0 °C was added

methylmagnesium bromide (450 mg, 5 mmol) drop wise. The reaction was stirred for 3 h at 0 °C, then the reaction mixture was quenched with sat aq NH₄CI solution and extracted with ethyl acetate. The combined EtOAc layer was washed with water and brine, dried over Na₂S0₄ and concentrated under reduced pressure. Purification by column chromatography (Si0₂, 100-200 mesh; 20 -25 EtOAc in petroleum ether) afforded the title compound as a solid (100 mg, 32%): ^]H NMR (400 MHz, CDC1₃) δ two diastereoisomers 8.58 (s, 1H, minor), 8.48 (s, 1H, major), 8.13 (s, 1H, minor), 8.09 (s, 1H, major), 7.70 (d, / = 9.0 Hz, 2H, minor), 7.53 (d, J = 9.0 Hz, 2H, minor), 7.40 (d, J = 9.0 Hz, 2H, major), 7.31 (m, 1H, minor), 7.27 (d, / = 9.0 Hz, 2H, major), 7.20 (m, 2H, minor), 7.01 (m, 1H, major), 6.75 (m, 2H, major), 350 (m, 1H), 2.50 (m, 2H), 1.56 (s, 3H, major), 1.54 (s, 3H, minor); ESIMS m/z 430.05 ([M+H]⁺).

Example 105: Preparation of (E)-l-(4-(4-(3,5-Dichlorophenyl)-5,5,5-trifluoropent-2-en- 2-yl)phenyl)-lH-l,2,4-triazol

To a solution of 2-(4-(lH-l ,2,4-triazol-l-yl)phenyl)-4-(3,5-dichlorophenyl)-5,5,5- trifluoropentan-2-ol (100 mg, 0.233 mmol) in toluene was added a catalytic amount of p- toluenesulfonic acid (PTSA) and the water was removed by azeotropic distillation over the course of 12 h. The reaction mixture was cooled to ambient temperature and dissolved in ethyl acetate. The solution was washed with sat aq NaHCC>3 solution and brine, dried over Na₂S0₄ and concentrated under reduced pressure. Purification by column chromatography (Si0₂, 100-200 mesh; 20%-25% EtOAc in petroleum ether) afforded the title compound as a solid (30 mg, 31%).

Example 123: Preparation of (£')-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-en-l- yl)-2-(lH-l,2,4-triazol-l-yl)benzaldehyde (DC52)

To a stirred solution of (£)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut- l-en-l-yl)-2- (lH-l ,2,4-triazol-l-yl)benzonitrile (0.3 g, 0.71 mmol) in toluene (10 mL) at -78 °C was added dropwise diisobutylaluminum hydride (DIBAL-H, 1.0 M solution in toluene; 0.85 mL), and the reaction mixture was stirred at -78 °C for 20 min. The reaction mixture was quenched with the addition of 1 N HCl solution, then the aqueous layer was extracted with EtOAc (2x). The combined organic layers were washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (Si0₂; 50% EtOAc/ Pet ether) to afford the title compound as a yellow oil.

Compound DC53 in Table 1 was made in accordance with the procedures disclosed in Example 123.

Example 124: Preparation of (£')-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-en-l- yl)- V-methyl-2-(lH-l,2,4-tr

To a stirred solution of (£)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l-en-l-yl)-2- (lH-l,2,4-triazol-l-yl)aniline (0.3 g, 0.7 mmol) in CH₂C1₂ (10 mL) was added TEA (0.155 mL, 1.09 mmol) and methyl iodide (0.124 g, 0.873 mmol). The reaction was stirred at ambient temperature for 18 h. The CH₂C1₂ layer was washed with water and brine, dried over Na₂S0₄ and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (Si0₂; 50% EtOAc/ Pet ether) to afford the title compound as a yellow semi-solid (0.07 g, 70%).

Example 125: Preparation of (£')-5-(3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-en-l- yl)-2-(lH-l,2,4-triazol-l-yl)b

A solution of (£ ethyl 5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l-en-l-yl)-2-(lH- l,2,4-triazol-l-yl)benzoate (0.2 g, 0.4 mmol) in 6 N HCl (10 mL) was stirred at 100 °C for 18 h. The reaction was cooled to ambient temperature, resulting in a white solid precipitate. The precipitate was filtered to afford the title compound as a white solid (0.12 g, 60%).

Example 126: Preparation of (Z)-5-((£)-3-(3,5-Dichlorophenyl)-4,4,4-trifluorobut-l-en- l.yl). V'-hydroxy-2-(lH-l,2,4-triazol-l-yl)benzimidamide (DC59)

A solution of (E)-5-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-l-en-l-yl)-2-(lH-l,2,4- triazol-l-yl)benzonitrile (0.3 g, 0.71 mmol), sodium acetate (0.087 g, 1.065 mmol) and hydroxylammonium chloride (0.072 g, 1.065 mmol) in 9: 1 ethanol/water mixture (10 mL) was stirred at 70 °C for 8 h. The reaction was cooled to ambient temperature, and the ethanol was evaporated. The residue was dissolved in water and extracted with EtOAc (2x). The combined organic layers were washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure to afford the title compound as an off white solid.

Example 127: Preparation of (£)-l-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluoro-3- methoxybut-l-en-l-yl)phenyl)-lH-l,2,4-triazole (DC70)

Step 1. (£)-3-(4-(lH-l,2,4-triazol-l-yl)phenyl)-l-(3,5-dichlorophenyl)prop-2-en-l- one: To a solution of l-(3,5-dichlorophenyl)ethanone (0.5 g, 2.6 mmol) in ethanol (20 mL) was added 4-(lH-l,2,4-triazol-l-yl)benzaldehyde (0.46 g, 2.65 mmol) and the reaction was cooled to 0 °C. Sodium hydroxide (0.22 g, 5.29 mmol) in water (10 mL) was then added and the reaction was allowed to stir for 2 h at 0 °C. The reaction was extracted with EtOAc and the combined organic layers were dried over Na₂S0₄ and concentrated under reduced pressure to afford the title compound (0.149 g, 17%): ); ESIMS m/z 430.05 ([M+H]⁺) 344.08 Step 2. (£)-4-(4-(lH-l,2,4-triazol-l-yl)phenyl)-2-(3,5-dichlorophenyl)-l,l,l- trifluorobut-3-en-2-ol (DC69): To a solution of (£)-3-(4-(lH-l,2,4-triazol-l-yl)phenyl)-l- (3,5-dichlorophenyl)prop-2-en-l-one (1 g, 3 mmol) in THF (150 mL) was added

trifluoromethyltrimethylsilane (0.517 g, 3.644 mmol) and tetra-n-butylammonium fluoride (TBAF) (1.0 M, 1 mL) at 0 °C. The reaction was slowly warmed to ambient temperature and allowed to stir for 2 h. The reaction was then cooled to 0 °C and 5 M HCl solution was added and the reaction was stirred for an additional 4 h at ambient temperature. The reaction was extracted with CH₂C1₂ and the combined organic layers were dried over Na₂S0₄ and concentrated under reduced pressure. The crude compound was purified by flash column chromatography (Si0₂; 25% EtOAc/ hexanes) to afford the title compound as an off-white solid (0.3 g, 25%).

Step 3. (£)-l-(4-(3-(3,5-Dichlorophenyl)-4,4,4-trifluoro-3-methoxybut-l-en-l- yl)phenyl)-lH-l,2,4-triazole (DC70): To a solution of (£ 4-(4-(lH-l,2,4-triazol-l- yl)phenyl)-2-(3,5-dichlorophenyl)-l,l,l-trifluorobut-3-en-2-ol (0.15 g, 0.36 mmol) in THF (5 mL) was added NaH (60%, 10 mg, 0.44 mmol) at 0 °C. The reaction was allowed to stir at 0 °C for 30 min, then methyl iodide (61 mg, 0.44 mmol) was added slowly and the reaction was warmed to ambient temperature and allowed to stir for 4 h. The reaction was quenched with aq NH₄CI solution and extracted with CH₂C1₂. The combined organic layers were dried over Na₂S0₄ and concentrated under reduced pressure to afford the title compound as an off-white solid (55 mg, 35%).

Prophetic Example Fll: Preparation of (£')-2-Bromo- V'-methyl- V'-propionyl-4-(4,4,4- trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)benzohydrazide (Fll)

Prophetically, (£)-2-bromo-4-(4,4,4-trifluoro-3 -(3 ,4,5 -trichlorophenyl)but- 1 -en- 1 - yl)benzoic acid can be reacted with N-methylpropionohydrazide in the presence of N-(3- dimethylaminopropyl)-N'-ethyl-carbodiimide hydrochloride (EDC^»HC1) and DMAP in 1,2- dichloroethane (DCE) to furnish the title molecule (Org. Lett. 2004, 6, 929-931).

Example 128: Preparation of (£')-2-Bromo- V'-methyl- V'-propionyl-4-(4,4,4-trifluoro-3- (3,4,5-trichlorophenyl)but- 1 -en-1 -yl)benzohydr azide (Fll)

To a stirred solution of (£)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl) but- 1-enyl) benzoic acid (200 mg, 0.41 mmol) in DCE (15 mL) was added N- methylpropionohydrazide (WO 2009110510) (50 mg, 0.49 mmol), DMAP (55 mg, 0.45 mmol), EDC'HCl (60 mg, 0.41 mmol) and DIPEA (0.20 mL, 1.1 mmol). The reaction mixture was stirred at 25 °C for 12 h, - diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure. Purification by flash column chromatography (Si0₂, 100-200 mesh) eluting with 30% EtOAc in hexane afforded the title compound as an off white solid (86 mg, 34 %). Example 129: Preparation of (£)- V-(2-Aminoethyl)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)benzamide

Step 1. (E)-tert-Butyl 2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but- l-enyl)benzamido)ethylcarbamate: PyBOP (420 mg, 0.82 mmol) and DIPEA (0.410 mL, 2.46 mmol) were added to a stirred solution of (E)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)benzoic acid (400 mg, 0.82 mmol) and ieri-butyl 2- aminoethylcarbamate (130 mg, 0.82 mmol) in CH₂C1₂ (10 mL) and the reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was partitioned between water and CH₂C1₂ (25 mL). The organic layer was washed with 2N HC1 followed by saturated NaHCC>3 and brine. The organic layer was dried (Na₂S0₄), filtered, concentrated and the residue was purified by column chromatography on silica (100-200 mesh) eluting with 40% EtOAc in petroleum ether to afford the title compound as a brown solid (200 mg, 39%): ^]H NMR (400 MHz, DMSO-rf₆) δ 8.38 (t, / = 5.2 Hz, 1H), 7.91 - 7.89 (m, 3H), 7.58 (d, / = 6.8 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 6.99 (dd, J = 15.6, 9.2 Hz, 1H), 6.84 (t, J = 6.0 Hz, 1H), 6.76 (t, 7 = 15.6 Hz, 1H), 4.84 - 4.80 (m, 1H), 3.24 - 3.20 (m, 2H), 3.11- 3.08 (m, 2H), 1.30 (s, 9H); ESIMS m/z 628.80 ([M+H]⁺); IR (thin film) 3365, 1701, 1167, 699, 555 cm^"1.

Step 2. (£)- V-(2-Aminoethyl)-2-bromo-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-enyl)benzamide: TFA ( 0.5 mL) was added to a stirred solution of (E)-tert-butyl 2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l- enyl)benzamido)ethylcarbamate (200 mg, 0.31 mmol) in CH₂C1₂ (10 mL) at 0 °C and the reaction mixture was then stirred at ambient temperature for 18 h. The volatiles were evaporated under reduced pressure; water was added to the residue and the mixture extracted with CH₂C1₂. The organic layer was washed with brine, dried (Na₂S0₄), filtered, concentrated and the residue was purified by column chromatography on silica (100-200 mesh) eluting with 1-5% MeOH in CH₂C1₂ to afford the title compound as a brown solid (50 mg, 31%): ^]H NMR (400 MHz, DMSO-d₆) δ 8.56 (bs, 1H), 7.70 (bs, 2H), 7.94 - 7.91 (m, 3H), 7.62 -7.59 (m, 1H), 7.50 (d, J = 7.6 Hz, 1H), 7.00 (dd, / = 15.6, 9.2 Hz, 1H), 6.77 (d, / = 15.6 Hz, 1H), 4.84 - 4.81 (m, 1H), 3.46- 3.41 (m, 2H), 2.95 - 2.92 (m, 2H); ESIMS mJz 528.72 ([M+H]⁺); IR (thin film) 3435, 1671, 1113, 722, 555 cm^"1.

The following compounds were made in accordance with the procedures disclosed in Step 2 of Example 129.

(£)- V-(2-Aminoethyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)-2- (trifluoromethyl)benzamide

Isolated as a brown semi solid: ^]H NMR (400 MHz, CDC1₃) δ 7.58 (s, 1H), 7.50 (s, 2H), 7.40 (s, 2H), 6.57 (d, / = 15.9 Hz, 1H), 6.41 (dd, / = 15.9, 7.9 Hz, 1H), 4.10 (p, / = 8.6 Hz, 1H), 3.52 (q, J = 5.2 Hz, 2H), 3.01 - 2.94 (m, 2H); ¹⁹F NMR (376 MHz, CDC1₃) δ - 59.11, -68.61 ; ESIMS mJz 521 ([M+H]⁺).

(£)- V-(l-Amino-2-methylpropan-2-yl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l- en-l-yl)-2-(trifluoromethyl)benzamide

Isolated as a brown semi solid: ^]H NMR (400 MHz, CDC1₃) δ 7.64 (d, / = 1.1 Hz, 1H), 7.56 (d, / = 1.6 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.41 (s, 2H), 6.61 (d, J = 15.9 Hz, 1H), 6.41 (dd, / = 15.9, 7.9 Hz, 1H), 6.29 (s, 1H), 4.11 (p, / = 8.6 Hz, 1H), 2.86 (s, 2H), 1.43 (s, 6H); ¹⁹F NMR (376 MHz, CDC1₃) δ -58.81, -68.61 ; ESIMS mJz 549 ([M+H]⁺).. Example 130: (£)-2-Bromo- V'-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l- enyl)-N'-(3,3,3-trifluoropropanoyl)benzohydrazide

Step 1. (£ fert-Butyl 2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but- l-enyl)benzoyl)-l-methylhydrazinecarboxylate: To a stirred solution of (£^')-2-bromo-4- (4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)benzoic acid (800 mg, 1.63 mmol) in DCE (15 mL) was added ieri-butyl hydrazinecarboxylate (290 mg, 1.96 mmol), DMAP (218 mg, 1.86 mmol), EDOHC1 (279 mg, 1.86 mmol) and DIPEA (0.8 mL, 4.89 mmol). The reaction mixture was stirred at 25 °C for 12 h, then diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure. Purification by flash column chromatography (Si0₂, 100-200 mesh; eluting with 30% hexane:EtOAc ) afforded the title compound as a brown gum (800 mg, 72%): ^]H NMR (300 MHz, DMSO-d₆) δ 10.5 (bs, 1H), 7.96 (s, 1H), 7.91 (s, 2H), 7.66 (d, / = 7.8 Hz, 1H), 7.37 (s, 1H), 7.03 (dd, J = 15.3, 8.7 Hz, 1H), 6.78 (d, J = 15.9 Hz, 1H), 4.87- 4.81 (m, 1H), 3.08 (s, 3H), 1.43 (s, 9H).

Step 2. (£)-2-Bromo-N'-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l- enyl)benzohydrazide: HCl (4M in dioxane) was added to a stirred solution of (£)-i<^?ri-butyl 2-(2-bromo-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)benzoyl)-l- methylhydrazinecarboxylate (1.0 g 1.6 mmol) in 1,4-dioxane (100 mL). The reaction mixture was stirred at ambient temperature for 4 h. The volatiles were evaporated and the residue was triturated with ether to afford the title compound as a light yellow solid (660, 99%): ^]H NMR (300 MHz, DMSO-d₆) 511.8 (s, 1H), 8.02 (s, 1H), 7.91 (s, 2H), 7.68 (d, / = 9.3 Hz, 2H), 7.52 (d, / = 8.1 Hz, 1H), 7.07 (dd, / = 15.6, 9.3 Hz, 1H), 6.78 (d, / = 15.3 Hz, 1H), 4.89- 4.83 (m, 1H), 2.81 (s, 3H); ESIMS m/z 517.0 ([M+H]⁺).

Step 3. (£)-2-Bromo-N'-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l- enyl)-N'-(3,3,3-trifluoropropanoyl)benzohydrazide: To a stirred solution of (£)-2-bromo- N-methyl-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-enyl)benzohydrazide (200 mg, 0.46 mmol) in DCE (15 mL), was added 3,3,3-trifluoropropanoic acid (59 mg, 0.38 mmol), DMAP (46 mg, 0.42 mmol), EDC'HCl (65 mg, 0.42 mmol) and DIPEA (0.2 mL, 1.16 mmol). The reaction mixture was stirred at 25 °C for 12 h, then diluted with water and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na₂S0₄ and concentrated under reduced pressure. Purification by flash column

chromatography (Si0₂, 100-200 mesh; eluting with 30 % hexane:EtOAc ) afforded the title compound as a yellow solid (50 mg, 25 %).

Example 131: Preparation of 4,4,4-Trifluoro-jV-methylbutanehydrazide

To a stirred solution of methylhydrazine (7.81 g, 169 mmol) in CH₂C1₂ (150 mL) cooled to 0 °C was added over 2 hours 4,4,4-trifluorobutanoyl chloride (2.72 g, 16.94 mmol, 0.3 M solution in CH2CI2) via a syringe pump. After the addition the reaction was stirred at 0 °C for - 1 h and then was allowed to warm to ambient temperature. After an additional hour of stirring at ambient temperature, the reaction mixture was poured into a - saturated aqueous solution of Na2CC>3 (400 mL). The organic layer was -separated and the -aqueous solution was extracted with additional CH2CI2 (1 x 150 mL). The -CH2CI2 layers -were -combined, dried over Na2S0_4> and concentrated under reduced pressure to afford the title compound as a yellow liquid: ^]H NMR (400 MHz, CDC1₃) major rotomer δ 3.77 (s, 2H), 3.20 (s, 3H), 2.93 - 2.85 (m, 2H), 2.48 - 2.33 (m, 2H); ¹³C NMR (101 MHz, CDC1₃) major rotomer δ 172.81 , 127.22 (q, 7 = 276.0 Hz), 29.55 (q, 7 = 29.4 Hz), 25.70 (q, 7 = 3.0 Hz); ¹⁹F NMR (376 MHz, CDCI₃) major rotomer δ -66.69.

Example 132: Preparation of (£)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l- yl)- V'-(4,4,4-trifluorobutanoyl)-2-(trifluoromethyl)benzohydrazide

Step 1. (£)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)-2- (trifluoromethyl)benzoyl chloride: To (£^')-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l- en-l-yl)-2-(trifluoromethyl)benzoic acid (3.048 g, 6.38 mmol) was added neat thionyl chloride (10 mL, 138 mmol)-and the reaction mixture was stirred at 80 °C for 1.5 h. The reaction mixture was concentrated under reduced pressure to afford the title compound as a red gummy residue: ^]H NMR (400 MHz, CDC1₃) δ 8.05 (d, 7 = 8.2 Hz, 1H), 7.83 - 7.75 (m, 1H), 7.70 (dd, 7 = 8.2, 1.7 Hz, 1H), 7.42 (s, 2H), 6.67 (d, 7 = 16.0 Hz, 1H), 6.55 (dd, 7 = 15.9, 7.6 Hz, 1H), 4.16 (p, 7 = 8.5 Hz, 1H); ¹⁹F NMR (376 MHz, CDC1₃) δ -59.59, -68.47; ¹³C NMR (101 MHz, CDCI₃) δ 165.62 , 140.39 , 135.01 , 134.03 , 133.68 (q, 7 = 1.8 Hz), 133.18 (q, 7 = 1.8 Hz), 132.29 , 132.20 , 129.63 , 129.13 (q, 7 = 33.4 Hz), 129.09, 126.32 (q, 7 = 2.4 Hz), 125.67 (q, 7 = 281.4 Hz), 125.28 (q, 7 = 5.6 Hz), 122.45 (q, 7 = 274.1 Hz), 52.38 (q, 7 = 28.9 Hz).

Step 2. (£)-4-(4,4,4-Trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)- V'-(4,4,4- trifluorobutanoyl)-2-(trifluoromethyl)benzohydrazide: To a stirred solution of (£)-4- (4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)-2-(trifluoromethyl)benzoyl chloride (143 mg, 0.288 mmol) in DCE (3 mL) were added 4,4,4-trifluorobutanehydrazide (45 mg, 0.29 mmol), and 4-methylmorpholine (63.4 \iL, 0.577 mmol), and the resultant reaction mixture was stirred at ambient temperature for 18 h. The reaction mixture was diluted with water and extracted with EtOAc (3 x 30 mL). The combined EtOAc layers were washed with aqueous 1M HC1 (- 1 x 30 mL), saturated aqueous NaHC0₃ (1 x 30 mL), and brine. The resulting organic solution was dried over Na₂S0₄ and concentrated under reduced pressure. Purification by automated flash column chromatography (Si0₂, hexanes and EtOAc) afforded the title compound as a beige solid (78 mg, 42%): ^]H NMR (400 MHz, CDC1₃) δ 10.23 (s, 1H), 9.85 (s, 1H), 7.70 - 7.62 (m, 1H), 7.55 (dd, / = 8.0, 1.6 Hz, 1H), 7.51 (d, / = 8.0 Hz, 1H), 7.41 (s, 2H), 6.59 (d, / = 15.9 Hz, 1H), 6.44 (dd, / = 15.9, 7.8 Hz, 1H), 4.19 - 4.05 (m, 1H), 2.51 (dd, / = 9.0, 6.6 Hz, 2H), 2.37 - 2.18 (m, 2H); ¹⁹F NMR (376 MHz, CDC13) δ - 59.46, -67.07, -68.59; ESIMS m/z 615 ([M-H]^").

The following compounds were made in accordance with the procedures disclosed in Step 2 of Example 132.

(£ fert-Butyl (2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)-2- (trifluoromethyl)benzamido)ethyl)carbamate

Isolated as a brown semi solid: ^]H NMR (400 MHz, CDC1₃) δ 7.67 (d, J = 1.6 Hz, 1H), 7.61 - 7.48 (m, 2H), 7.42 (s, 2H), 6.62 (d, J = 15.9 Hz, 1H), 6.52 (s, 1H), 6.43 (dd, J = 15.9, 7.9 Hz, 1H), 4.90 (s, 1H), 4.12 (p, / = 8.7 Hz, 1H), 3.56 (q, / = 5.5 Hz, 2H), 3.38 (q, J 6.1 Hz, 2H), 1.42 (s, 9H); ¹⁹F NMR (376 MHz, CDC1₃) δ -59.11, -68.58; ESIMS m/z 619 «M+H]⁺).

(£)- V-(2-Amino-2-methylpropyl)-4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l yl)-2-(trifluoromethyl)benzamide

Isolated as a dark green solid: mp 55-65 °C; ^]H NMR (400 MHz, CDC1₃) δ 7.66 (s, 1H), 7.57 (d, J = 8.2 Hz, 1H), 7.53 (d, J = 7.7 Hz, 1H), 7.42 (s, 2H), 6.61 (d, J = 15.9 Hz, 1H), 6.42 (dd, J = 15.9, 7.9 Hz, 1H), 4.12 (p, J = 8.6 Hz, 1H), 3.33 (d, J = 5.7 Hz, 2H), 2.05 (s, 1H), 1.17 (s, 6H); ¹⁹F NMR (376 MHz, CDC1₃) δ -59.02, -68.60; ESIMS m/z 548 «M+H]⁺). (E)-tert-Butyl (2-methyl-2-(4-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-l-en-l-yl)-2- (trifluoromethyl)benzamido)propyl)carbamate

Isolated as a brown semi solid: ^]H NMR (400 MHz, CDC1₃) δ 7.67 - 7.61 (m, 1H), 7.57 - 7.49 (m, 1H), 7.45 (d, J = 7.9 Hz, 1H), 7.41 (s, 2H), 6.69 (s, 1H), 6.61 (d, J = 15.9 Hz, 1H), 6.41 (dd, / = 15.9, 7.8 Hz, 1H), 5.13 (t, J = 6.4 Hz, 1H), 4.12 (p, / = 8.6 Hz, 1H), 3.29 (d, J = 6.7 Hz, 2H), 1.45 (s, 6H), 1.40 (s, 9H); ¹⁹F NMR (376 MHz, CDC1₃) δ -59.02, rotomers -68.58 & -68.60; ESIMS m/z 647 ([M+H]⁺).

Example 133: Preparation of jV-Methylbutanehydrazide

O

H₂N,

To a stirred solution of methylhydrazine (4.48 mL, 85 mmol) in CH₂CI₂ (57 mL) cooled to 0 °C was added over 2 h butyric anhydride (1.39 mL, 8.5 mmol, 0.3 M solution in CH₂CI₂) via a syringe pump. After the addition the reaction was stirred at 0 °C for 1 h and then was allowed to stir overnight while slowly warming to ambient temperature. The reaction mixture was poured into a solution of saturated Na₂CC>3 (200 mL). The organic layer was separated, dried over Na₂S0_4> and concentrated under reduced pressure to afford the title compound as a yellow liquid: ^]H NMR (400 MHz, CDC1₃) major rotomer δ 4.47 (s, 2H), 3.21 (s, 3H), 2.31 (dd, / = 8.1, 7.0 Hz, 2H), 1.66 (h, / = 7.5 Hz, 2H); ¹³C NMR (101 MHz, CDCI₃) major rotomer δ 171.67, 38.48, 34.76, 18.74, 13.90; EIMS m/z 116 ([M]⁺). Example 134: Preparation of jV-Meth ecarbohydrazide

Step 1. Benzyl 2-(cyclopropanecarbonyl)-2-methylhydrazinecarboxylate:

Cyclopropanecarboxylic acid (600 mg, 6.97 mmol), DMAP (170 mg, 1.39 mmol) and EDOHC1 (1.19 g, 7.67 mmol) were added in that order to a stirred solution of benzyl 2- methylhydrazinecarboxylate hydrochloride {JOC, 2013, 78, 3541-3552.) (1.80 g, 8.37 mmol) in DCE (10 mL) and the reaction mixture was stirred at 25 °C for 12 h. Water was added to the reaction mixture and the mixture extracted with EtOAc. The organic layer was washed with brine, dried (Na₂S0₄), filtered, concentrated and the residue was purified by column chromatography on silica (100-200 mesh) eluting with 30 % hexane in EtOAc to afford the title compound as a colourless gum (1.6 g, 80 %): 1H NMR (300 MHz, DMSO-d₆) 510.01 (bs, 1H), 7.37 (s, 5 H), 5.18 (s, 2H), 2.97 (s, 3H ), 1.98 - 1.89 (m, 1H), 0.70 - 0.68 (m, 4H); ESIMS m/z 247. ,0 ([M-H]^"); IR (thin film) 3502, 2928, 1736 cm^"1.

Step 2. N-Methylcyclopropanecarbohydrazide: 10 % Pd/C (- 0.16 g) was added to a stirred solution of benzyl 2-(cyclopropanecarbonyl)-2-methylhydrazinecarboxylate (1.6 g, 6.45 mmol) in MeOH (10 mL). The reaction mixture was stirred -under hydrogen - (20 psi) for 3 h. The volatiles were evaporated and the residue was triturated with Et₂0 to afford the title compound as a yellow liquid (700 mg, 95 %): ^]H NMR (400 MHz, DMSO-d₆) δ 4.75 (bs, 2H), 3.00 (s, 3H), 2.71-2.68 (m, 1H), 0.70 - 0.62 (m, 4H). ESIMS m/z 114.2 ([M+H]⁺); IR (thin film) 3321, 1633 cm^"1.

Example 135: Preparation of (£)- V-(2-Methyl-2-(2,2,2-trifluoroacetamido)propyl)-4- (4,4,4-trifluoro-3-(3,4,5 richlorophenyl)but-l-en-l-yl)-2-(trifluoromethyl)benzamide

To -a solution of (£)-N-(2-amino-2-methylpropyl)-4-(4,4,4-trifluoro-3-(3,4,5- trichlorophenyl)but-l-en-l-yl)-2-(trifluoromethyl)benzamide (155 mg, 0.283 mmol), 1- [bis(dimethylamino)methylene]-lH-l,2,3-triazolo[4,5-^]pyridinium 3-oxid

hexafluorophosphate (HATU) (118 mg, 0.311 mmol), and 2,2,2-trifluoroacetic acid (0.026 mL, 0.340 mmol) in DMF (1 mL) was -added N-methylmorpholine (0.062 mL, 0.566 mmol). The mixture was stirred at ambient temperature for 18 h, -then partitioned between water and EtOAc. The organic phase was washed with water and -brine, - dried (sodium sulfate) and concentrated -under reduced pressure. Purification by column chromatography eluting with EtOAc in hexanes (10%-100%) - afforded the title compound as a yellow oil (26 mg, 13%). Example 136: Preparation of 2,2,3, -Heptafluoro-N-methylbutanehydrazide

Methylhydrazine (4.5 mL, 85 mmol) in CH₂C1₂ (57 mL) was cooled -at 0° C. -To this was added a 0.15 M - solution of 2,2,3, 3,4,4,4-heptafluorobutanoic anhydride (35 g, 8.5 mmol) in CH₂C1₂ over 2 h via a syringe pump. After the addition was complete, the reaction was slowly warmed to ambient temperature. After 18 h the mixture was washed a -saturated solution of Na₂C0₃. (225 mL). The organic layer was dried with Na₂S0₄ and concentrated in vacuo to afford the title compound as yellow oil (840 mg, 36%): ^]H NMR (400 MHz, CDC1₃) δ 3.93 (s, 2H), 3.29 (t, J = 0.9 Hz, 3H); ¹⁹F NMR (376 MHz, CDC1₃) major rotomer δ -80.58 (t, J = 9.8 Hz), -112.70 - -112.94 (m), -123.59 - -123.70 (m); EIMS mJz 242 ([M]⁺).

The following prophetic molecules could be made in accordance with the procedures disclosed in Prophetic Example Fl l :

The following prophetic molecules could be made in accordance with the procedures disclosed in this application:

F56 F F F H CF₃ H S CH₂CH₃

F57 F F F H CH₃ H S CH₂CH₃

F58 F F F H Br CH₃ s CH₂CH₃

F59 F F F H CI CH₃ s CH₂CH₃

F60 F F F H CF₃ CH₃ s CH₂CH₃

F61 F F F H CH₃ CH₃ s CH₂CH₃

F62 F F F H Br CH₃ 0 CH₂CH₃

F63 F F F H CI CH₃ 0 CH₂CH₃

F64 F F F H CF₃ CH₃ 0 CH₂CH₃

F65 F F F H CH₃ CH₃ 0 CH₂CH₃

F66 F F F H Br CH₃ 0 CH₂CN

F67 F F F H CI CH₃ 0 CH₂CN

F68 F F F H CF₃ CH₃ 0 CH₂CN

F69 F F F H CH₃ CH₃ 0 CH₂CN

F70 F F F H Br CH₃ s cyclopropyl

F71 F F F H CI CH₃ s cyclopropyl

F72 F F F H CF₃ CH₃ s cyclopropyl

F73 F F F H CH₃ CH₃ s cyclopropyl

F74 CI CI H CI Br H 0 CH₂CF₃

F75 CI CI H CI CI H 0 CH₂CF₃

F76 CI CI H CI CF₃ H 0 CH₂CF₃

F77 CI CI H CI CH₃ H 0 CH₂CF₃

F78 CI CI H CI Br H 0 cyclopropyl

F79 CI CI H CI CI H 0 cyclopropyl

F80 CI CI H CI CF₃ H 0 cyclopropyl

F81 CI CI H CI CH₃ H 0 cyclopropyl F108 H H H OCF₃ CF₃ H 0 CH2CF3

F109 H H H OCF3 CH₃ H 0 CH2CF3

F110 H H H OCF3 Br H 0 cyclopropyl

Fill H H H OCF3 CI H 0 cyclopropyl

F112 H H H OCF3 CF₃ H 0 cyclopropyl

F113 H H H OCF3 CH₃ H 0 cyclopropyl

F114 H H H OCF3 Br H 0 CH2CH3

F115 H H H OCF3 CI H 0 CH2CH3

F116 H H H OCF₃ CF₃ H 0 CH₂CH₃

F117 H H H OCF3 CH₃ H 0 CH2CH3

F118 H H H OCF3 Br H s CH2CH3

F119 H H H OCF3 CI H s CH2CH3

F120 H H H OCF₃ CF₃ H s CH₂CH₃

F121 H H H OCF₃ CH₃ H s CH₂CH₃

F122 H H H OCF3 Br CH₃ s CH2CH3

F123 H H H OCF3 CI CH₃ s CH2CH3

F124 H H H OCF3 CF₃ CH₃ s CH2CH3

F125 H H H OCF₃ CH₃ CH₃ s CH₂CH₃

F126 H H H OCF3 Br CH₃ 0 CH2CH3

F127 H H H OCF3 CI CH₃ 0 CH2CH3

F128 H H H OCF3 CF₃ CH₃ 0 CH2CH3

F129 H H H OCF3 CH₃ CH₃ 0 CH2CH3

F130 H H H OCF₃ Br CH₃ 0 CH₂CN

F131 H H H OCF3 CI CH₃ 0 CH₂CN

F132 H H H OCF3 CF₃ CH₃ 0 CH₂CN

F133 H H H OCF3 CH₃ CH₃ 0 CH₂CN F160 H F H Br CF₃ CH₃ 0 CH₂CH₃

F161 H F H Br CH₃ CH₃ 0 CH₂CH₃

F162 H F H Br Br CH₃ 0 CH₂CN

F163 H F H Br CI CH₃ 0 CH₂CN

F164 H F H Br CF₃ CH₃ 0 CH₂CN

F165 H F H Br CH₃ CH₃ 0 CH₂CN

F166 H F H Br Br CH₃ S cyclopropyl

F167 H F H Br CI CH₃ s cyclopropyl

F168 H F H Br CF₃ CH₃ s cyclopropyl

F169 H F H Br CH₃ CH₃ s cyclopropyl

F170 H CH₃ CI H Br H 0 CH₂CF₃

F171 H CH₃ CI H CI H 0 CH₂CF₃

F172 H CH₃ CI H CF₃ H 0 CH₂CF₃

F173 H CH₃ CI H CH₃ H 0 CH₂CF₃

F174 H CH₃ CI H Br H 0 cyclopropyl

F175 H CH₃ CI H CI H 0 cyclopropyl

F176 H CH₃ CI H CF₃ H 0 cyclopropyl

F177 H CH₃ CI H CH₃ H 0 cyclopropyl

F178 H CH₃ CI H Br H 0 CH₂CH₃

F179 H CH₃ CI H CI H 0 CH₂CH₃

F180 H CH₃ CI H CF₃ H 0 CH₂CH₃

F181 H CH₃ CI H CH₃ H 0 CH₂CH₃

F182 H CH₃ CI H Br H s CH₂CH₃

F183 H CH₃ CI H CI H s CH₂CH₃

F184 H CH₃ CI H CF₃ H s CH₂CH₃

F185 H CH₃ CI H CH₃ H s CH₂CH₃ F186 H CH₃ CI H Br CH₃ S CH₂CH₃

F187 H CH₃ CI H CI CH₃ S CH₂CH₃

F188 H CH₃ CI H CF₃ CH₃ s CH₂CH₃

F189 H CH₃ CI H CH₃ CH₃ s CH₂CH₃

F190 H CH₃ CI H Br CH₃ 0 CH₂CH₃

F191 H CH₃ CI H CI CH₃ 0 CH₂CH₃

F192 H CH₃ CI H CF₃ CH₃ 0 CH₂CH₃

F193 H CH₃ CI H CH₃ CH₃ 0 CH₂CH₃

F194 H CH₃ CI H Br CH₃ 0 CH₂CN

F195 H CH₃ CI H CI CH₃ 0 CH₂CN

F196 H CH₃ CI H CF₃ CH₃ 0 CH₂CN

F197 H CH₃ CI H CH₃ CH₃ 0 CH₂CN

F198 H CH₃ CI H Br CH₃ s cyclopropyl

F199 H CH₃ CI H CI CH₃ s cyclopropyl

F200 H CH₃ CI H CF₃ CH₃ s cyclopropyl

F201 H CH₃ CI H CH₃ CH₃ s cyclopropyl

F202 H CI CH₃ H Br H 0 CH₂CF₃

F203 H CI CH₃ H CI H 0 CH₂CF₃

F204 H CI CH₃ H CF₃ H 0 CH₂CF₃

F205 H CI CH₃ H CH₃ H 0 CH₂CF₃

F206 H CI CH₃ H Br H 0 cyclopropyl

F207 H CI CH₃ H CI H 0 cyclopropyl

F208 H CI CH₃ H CF₃ H 0 cyclopropyl

F209 H CI CH₃ H CH₃ H 0 cyclopropyl

F210 H CI CH₃ H Br H 0 CH₂CH₃

F211 H CI CH₃ H CI H 0 CH₂CH₃ F212 H CI CH₃ H CF₃ H 0 CH₂CH₃

F213 H CI CH₃ H CH₃ H 0 CH₂CH₃

F214 H CI CH₃ H Br H S CH₂CH₃

F215 H CI CH₃ H CI H s CH₂CH₃

F216 H CI CH₃ H CF₃ H s CH₂CH₃

F217 H CI CH₃ H CH₃ H s CH₂CH₃

F218 H CI CH₃ H Br CH₃ s CH₂CH₃

F219 H CI CH₃ H CI CH₃ s CH₂CH₃

F220 H CI CH₃ H CF₃ CH₃ s CH₂CH₃

F221 H CI CH₃ H CH₃ CH₃ s CH₂CH₃

F222 H CI CH₃ H Br CH₃ 0 CH₂CH₃

F223 H CI CH₃ H CI CH₃ 0 CH₂CH₃

F224 H CI CH₃ H CF₃ CH₃ 0 CH₂CH₃

F225 H CI CH₃ H CH₃ CH₃ 0 CH₂CH₃

F226 H CI CH₃ H Br CH₃ 0 CH₂CN

F227 H CI CH₃ H CI CH₃ 0 CH₂CN

F228 H CI CH₃ H CF₃ CH₃ 0 CH₂CN

F229 H CI CH₃ H CH₃ CH₃ 0 CH₂CN

F230 H CI CH₃ H Br CH₃ s cyclopropyl

F231 H CI CH₃ H CI CH₃ s cyclopropyl

F232 H CI CH₃ H CF₃ CH₃ s cyclopropyl

F233 H CI CH₃ H CH₃ CH₃ s cyclopropyl

F234 H CH₃ F CH₃ Br H 0 CH₂CF₃

F235 H CH₃ F CH₃ CI H 0 CH₂CF₃

F236 H CH₃ F CH₃ CF₃ H 0 CH₂CF₃

F237 H CH₃ F CH₃ CH₃ H 0 CH₂CF₃ F238 H CH₃ F CH₃ Br H 0 cyclopropyl

F239 H CH₃ F CH₃ CI H 0 cyclopropyl

F240 H CH₃ F CH₃ CF₃ H 0 cyclopropyl

F241 H CH₃ F CH₃ CH₃ H 0 cyclopropyl

F242 H CH₃ F CH₃ Br H 0 CH₂CH₃

F243 H CH₃ F CH₃ CI H 0 CH₂CH₃

F244 H CH₃ F CH₃ CF₃ H 0 CH₂CH₃

F245 H CH₃ F CH₃ CH₃ H 0 CH₂CH₃

F246 H CH₃ F CH₃ Br H s CH₂CH₃

F247 H CH₃ F CH₃ CI H s CH₂CH₃

F248 H CH₃ F CH₃ CF₃ H s CH₂CH₃

F249 H CH₃ F CH₃ CH₃ H s CH₂CH₃

F250 H CH₃ F CH₃ Br CH₃ s CH₂CH₃

F251 H CH₃ F CH₃ CI CH₃ s CH₂CH₃

F252 H CH₃ F CH₃ CF₃ CH₃ s CH₂CH₃

F253 H CH₃ F CH₃ CH₃ CH₃ s CH₂CH₃

F254 H CH₃ F CH₃ Br CH₃ 0 CH₂CH₃

F255 H CH₃ F CH₃ CI CH₃ 0 CH₂CH₃

F256 H CH₃ F CH₃ CF₃ CH₃ 0 CH₂CH₃

F257 H CH₃ F CH₃ CH₃ CH₃ 0 CH₂CH₃

F258 H CH₃ F CH₃ Br CH₃ 0 CH₂CN

F259 H CH₃ F CH₃ CI CH₃ 0 CH₂CN

F260 H CH₃ F CH₃ CF₃ CH₃ 0 CH₂CN

F261 H CH₃ F CH₃ CH₃ CH₃ 0 CH₂CN

F262 H CH₃ F CH₃ Br CH₃ s cyclopropyl

F263 H CH₃ F CH₃ CI CH₃ s cyclopropyl F264 H CH₃ F CH₃ CF₃ CH₃ S cyclopropyl

F265 H CH₃ F CH₃ CH₃ CH₃ s cyclopropyl

F266 H CI H Br Br H 0 CH₂CF₃

F267 H CI H Br CI H 0 CH₂CF₃

F268 H CI H Br CF₃ H 0 CH₂CF₃

F269 H CI H Br CH₃ H 0 CH₂CF₃

F270 H CI H Br Br H 0 cyclopropyl

F271 H CI H Br CI H 0 cyclopropyl

F272 H CI H Br CF₃ H 0 cyclopropyl

F273 H CI H Br CH₃ H 0 cyclopropyl

F274 H CI H Br Br H 0 CH₂CH₃

F275 H CI H Br CI H 0 CH₂CH₃

F276 H CI H Br CF₃ H 0 CH₂CH₃

F277 H CI H Br CH₃ H 0 CH₂CH₃

F278 H CI H Br Br H s CH₂CH₃

F279 H CI H Br CI H s CH₂CH₃

F280 H CI H Br CF₃ H s CH₂CH₃

F281 H CI H Br CH₃ H s CH₂CH₃

F282 H CI H Br Br CH₃ s CH₂CH₃

F283 H CI H Br CI CH₃ s CH₂CH₃

F284 H CI H Br CF₃ CH₃ s CH₂CH₃

F285 H CI H Br CH₃ CH₃ s CH₂CH₃

F286 H CI H Br Br CH₃ 0 CH₂CH₃

F287 H CI H Br CI CH₃ 0 CH₂CH₃

F288 H CI H Br CF₃ CH₃ 0 CH₂CH₃

F289 H CI H Br CH₃ CH₃ 0 CH₂CH₃ F290 H CI H Br Br CH₃ 0 CH₂CN

F291 H CI H Br CI CH₃ 0 CH₂CN

F292 H CI H Br CF₃ CH₃ 0 CH₂CN

F293 H CI H Br CH₃ CH₃ 0 CH₂CN

F294 H CI H Br Br CH₃ S cyclopropyl

F295 H CI H Br CI CH₃ s cyclopropyl

F296 H CI H Br CF₃ CH₃ s cyclopropyl

F297 H CI H Br CH₃ CH₃ s cyclopropyl

F298 H H Br Br Br H 0 CH₂CF₃

F299 H H Br Br CI H 0 CH₂CF₃

F300 H H Br Br CF₃ H 0 CH₂CF₃

F301 H H Br Br CH₃ H 0 CH₂CF₃

F302 H H Br Br Br H 0 cyclopropyl

F303 H H Br Br CI H 0 cyclopropyl

F304 H H Br Br CF₃ H 0 cyclopropyl

F305 H H Br Br CH₃ H 0 cyclopropyl

F306 H H Br Br Br H 0 CH₂CH₃

F307 H H Br Br CI H 0 CH₂CH₃

F308 H H Br Br CF₃ H 0 CH₂CH₃

F309 H H Br Br CH₃ H 0 CH₂CH₃

F310 H H Br Br Br H s CH₂CH₃

F311 H H Br Br CI H s CH₂CH₃

F312 H H Br Br CF₃ H s CH₂CH₃

F313 H H Br Br CH₃ H s CH₂CH₃

F314 H H Br Br Br CH₃ s CH₂CH₃

F315 H H Br Br CI CH₃ s CH₂CH₃ F316 H H Br Br CF₃ CH₃ S CH₂CH₃

F317 H H Br Br CH₃ CH₃ S CH₂CH₃

F318 H H Br Br Br CH₃ 0 CH₂CH₃

F319 H H Br Br CI CH₃ 0 CH₂CH₃

F320 H H Br Br CF₃ CH₃ 0 CH₂CH₃

F321 H H Br Br CH₃ CH₃ 0 CH₂CH₃

F322 H H Br Br Br CH₃ 0 CH₂CN

F323 H H Br Br CI CH₃ 0 CH₂CN

F324 H H Br Br CF₃ CH₃ 0 CH₂CN

F325 H H Br Br CH₃ CH₃ 0 CH₂CN

F326 H H Br Br Br CH₃ s cyclopropyl

F327 H H Br Br CI CH₃ s cyclopropyl

F328 H H Br Br CF₃ CH₃ s cyclopropyl

F329 H H Br Br CH₃ CH₃ s cyclopropyl

F330 H H CI N0₂ Br H 0 CH₂CF₃

F331 H H CI N0₂ CI H 0 CH₂CF₃

F332 H H CI N0₂ CF₃ H 0 CH₂CF₃

F333 H H CI N0₂ CH₃ H 0 CH₂CF₃

F334 H H CI N0₂ Br H 0 cyclopropyl

F335 H H CI N0₂ CI H 0 cyclopropyl

F336 H H CI N0₂ CF₃ H 0 cyclopropyl

F337 H H CI N0₂ CH₃ H 0 cyclopropyl

F338 H H CI N0₂ Br H 0 CH₂CH₃

F339 H H CI N0₂ CI H 0 CH₂CH₃

F340 H H CI N0₂ CF₃ H 0 CH₂CH₃

F341 H H CI N0₂ CH₃ H 0 CH₂CH₃ F342 H H CI N0₂ Br H S CH₂CH₃

F343 H H CI N0₂ CI H S CH₂CH₃

F344 H H CI N0₂ CF₃ H s CH₂CH₃

F345 H H CI N0₂ CH₃ H s CH₂CH₃

F346 H H CI N0₂ Br CH₃ s CH₂CH₃

F347 H H CI N0₂ CI CH₃ s CH₂CH₃

F348 H H CI N0₂ CF₃ CH₃ s CH₂CH₃

F349 H H CI N0₂ CH₃ CH₃ s CH₂CH₃

F350 H H CI N0₂ Br CH₃ 0 CH₂CH₃

F351 H H CI N0₂ CI CH₃ 0 CH₂CH₃

F352 H H CI N0₂ CF₃ CH₃ 0 CH₂CH₃

F353 H H CI N0₂ CH₃ CH₃ 0 CH₂CH₃

F354 H H CI N0₂ Br CH₃ 0 CH₂CN

F355 H H CI N0₂ CI CH₃ 0 CH₂CN

F356 H H CI N0₂ CF₃ CH₃ 0 CH₂CN

F357 H H CI N0₂ CH₃ CH₃ 0 CH₂CN

F358 H H CI N0₂ Br CH₃ s cyclopropyl

F359 H H CI N0₂ CI CH₃ s cyclopropyl

F360 H H CI N0₂ CF₃ CH₃ s cyclopropyl

F361 H H CI N0₂ CH₃ CH₃ s cyclopropyl

F362 H H F CN Br H 0 CH₂CF₃

F363 H H F CN CI H 0 CH₂CF₃

F364 H H F CN CF₃ H 0 CH₂CF₃

F365 H H F CN CH₃ H 0 CH₂CF₃

F366 H H F CN Br H 0 cyclopropyl

F367 H H F CN CI H 0 cyclopropyl F368 H H F CN CF₃ H 0 cyclopropyl

F369 H H F CN CH₃ H 0 cyclopropyl

F370 H H F CN Br H 0 CH₂CH₃

F371 H H F CN CI H 0 CH₂CH₃

F372 H H F CN CF₃ H 0 CH₂CH₃

F373 H H F CN CH₃ H 0 CH₂CH₃

F374 H H F CN Br H s CH₂CH₃

F375 H H F CN CI H s CH₂CH₃

F376 H H F CN CF₃ H s CH₂CH₃

F377 H H F CN CH₃ H s CH₂CH₃

F378 H H F CN Br CH₃ s CH₂CH₃

F379 H H F CN CI CH₃ s CH₂CH₃

F380 H H F CN CF₃ CH₃ s CH₂CH₃

F381 H H F CN CH₃ CH₃ s CH₂CH₃

F382 H H F CN Br CH₃ 0 CH₂CH₃

F383 H H F CN CI CH₃ 0 CH₂CH₃

F384 H H F CN CF₃ CH₃ 0 CH₂CH₃

F385 H H F CN CH₃ CH₃ 0 CH₂CH₃

F386 H H F CN Br CH₃ 0 CH₂CN

F387 H H F CN CI CH₃ 0 CH₂CN

F388 H H F CN CF₃ CH₃ 0 CH₂CN

F389 H H F CN CH₃ CH₃ 0 CH₂CN

F390 H H F CN Br CH₃ s cyclopropyl

F391 H H F CN CI CH₃ s cyclopropyl

F392 H H F CN CF₃ CH₃ s cyclopropyl

F393 H H F CN CH₃ CH₃ s cyclopropyl F394 H CI OCF₃ CI Br H 0 CH2CF3

F395 H CI OCF3 CI CI H 0 CH2CF3

F396 H CI OCF3 CI CF₃ H 0 CH2CF3

F397 H CI OCF3 CI CH₃ H 0 CH2CF3

F398 H CI OCF3 CI Br H 0 cyclopropyl

F399 H CI OCF3 CI CI H 0 cyclopropyl

F400 H CI OCF3 CI CF₃ H 0 cyclopropyl

F401 H CI OCF3 CI CH₃ H 0 cyclopropyl

F402 H CI OCF₃ CI Br H 0 CH₂CH₃

F403 H CI OCF3 CI CI H 0 CH2CH3

F404 H CI OCF3 CI CF₃ H 0 CH2CH3

F405 H CI OCF3 CI CH₃ H 0 CH2CH3

F406 H CI OCF₃ CI Br H s CH₂CH₃

F407 H CI OCF₃ CI CI H s CH₂CH₃

F408 H CI OCF3 CI CF₃ H s CH2CH3

F409 H CI OCF3 CI CH₃ H s CH2CH3

F410 H CI OCF3 CI Br CH₃ s CH2CH3

F411 H CI OCF₃ CI CI CH₃ s CH₂CH₃

F412 H CI OCF3 CI CF₃ CH₃ s CH2CH3

F413 H CI OCF3 CI CH₃ CH₃ s CH2CH3

F414 H CI OCF3 CI Br CH₃ 0 CH2CH3

F415 H CI OCF3 CI CI CH₃ 0 CH2CH3

F416 H CI OCF₃ CI CF₃ CH₃ 0 CH₂CH₃

F417 H CI OCF3 CI CH₃ CH₃ 0 CH2CH3

F418 H CI OCF3 CI Br CH₃ 0 CH₂CN

F419 H CI OCF3 CI CI CH₃ 0 CH₂CN F420 H CI OCF₃ CI CF₃ CH₃ 0 CH₂CN

F421 H CI OCF3 CI CH₃ CH₃ 0 CH₂CN

F422 H CI OCF3 CI Br CH₃ S cyclopropyl

F423 H CI OCF3 CI CI CH₃ s cyclopropyl

F424 H CI OCF3 CI CF₃ CH₃ s cyclopropyl

F425 H CI OCF3 CI CH₃ CH₃ s cyclopropyl

F426 H CI CN CI Br H 0 CH2CF3

F427 H CI CN CI CI H 0 CH2CF3

F428 H CI CN CI CF₃ H 0 CH₂CF₃

F429 H CI CN CI CH₃ H 0 CH2CF3

F430 H CI CN CI Br H 0 cyclopropyl

F431 H CI CN CI CI H 0 cyclopropyl

F432 H CI CN CI CF₃ H 0 cyclopropyl

F433 H CI CN CI CH₃ H 0 cyclopropyl

F434 H CI CN CI Br H 0 CH2CH3

F435 H CI CN CI CI H 0 CH2CH3

F436 H CI CN CI CF₃ H 0 CH2CH3

F437 H CI CN CI CH₃ H 0 CH₂CH₃

F438 H CI CN CI Br H s CH2CH3

F439 H CI CN CI CI H s CH2CH3

F440 H CI CN CI CF₃ H s CH2CH3

F441 H CI CN CI CH₃ H s CH2CH3

F442 H CI CN CI Br CH₃ s CH₂CH₃

F443 H CI CN CI CI CH₃ s CH2CH3

F444 H CI CN CI CF₃ CH₃ s CH2CH3

F445 H CI CN CI CH₃ CH₃ s CH2CH3 F446 H CI CN CI Br CH₃ 0 CH₂CH₃

F447 H CI CN CI CI CH₃ 0 CH₂CH₃

F448 H CI CN CI CF₃ CH₃ 0 CH₂CH₃

F449 H CI CN CI CH₃ CH₃ 0 CH₂CH₃

F450 H CI CN CI Br CH₃ 0 CH₂CN

F451 H CI CN CI CI CH₃ 0 CH₂CN

F452 H CI CN CI CF₃ CH₃ 0 CH₂CN

F453 H CI CN CI CH₃ CH₃ 0 CH₂CN

F454 H CI CN CI Br CH₃ s cyclopropyl

F455 H CI CN CI CI CH₃ s cyclopropyl

F456 H CI CN CI CF₃ CH₃ s cyclopropyl

F457 H CI CN CI CH₃ CH₃ s cyclopropyl

F458 H CH₃ H Br Br H 0 CH₂CF₃

F459 H CH₃ H Br CI H 0 CH₂CF₃

F460 H CH₃ H Br CF₃ H 0 CH₂CF₃

F461 H CH₃ H Br CH₃ H 0 CH₂CF₃

F462 H CH₃ H Br Br H 0 cyclopropyl

F463 H CH₃ H Br CI H 0 cyclopropyl

F464 H CH₃ H Br CF₃ H 0 cyclopropyl

F465 H CH₃ H Br CH₃ H 0 cyclopropyl

F466 H CH₃ H Br Br H 0 CH₂CH₃

F467 H CH₃ H Br CI H 0 CH₂CH₃

F468 H CH₃ H Br CF₃ H 0 CH₂CH₃

F469 H CH₃ H Br CH₃ H 0 CH₂CH₃

F470 H CH₃ H Br Br H s CH₂CH₃

F471 H CH₃ H Br CI H s CH₂CH₃ F472 H CH₃ H Br CF₃ H S CH₂CH₃

F473 H CH₃ H Br CH₃ H S CH₂CH₃

F474 H CH₃ H Br Br CH₃ s CH₂CH₃

F475 H CH₃ H Br CI CH₃ s CH₂CH₃

F476 H CH₃ H Br CF₃ CH₃ s CH₂CH₃

F477 H CH₃ H Br CH₃ CH₃ s CH₂CH₃

F478 H CH₃ H Br Br CH₃ 0 CH₂CH₃

F479 H CH₃ H Br CI CH₃ 0 CH₂CH₃

F480 H CH₃ H Br CF₃ CH₃ 0 CH₂CH₃

F481 H CH₃ H Br CH₃ CH₃ 0 CH₂CH₃

F482 H CH₃ H Br Br CH₃ 0 CH₂CN

F483 H CH₃ H Br CI CH₃ 0 CH₂CN

F484 H CH₃ H Br CF₃ CH₃ 0 CH₂CN

F485 H CH₃ H Br CH₃ CH₃ 0 CH₂CN

F486 H CH₃ H Br Br CH₃ s cyclopropyl

F487 H CH₃ H Br CI CH₃ s cyclopropyl

F488 H CH₃ H Br CF₃ CH₃ s cyclopropyl

F489 H CH₃ H Br CH₃ CH₃ s cyclopropyl

F490 H H F CH₃ Br H 0 CH₂CF₃

F491 H H F CH₃ CI H 0 CH₂CF₃

F492 H H F CH₃ CF₃ H 0 CH₂CF₃

F493 H H F CH₃ CH₃ H 0 CH₂CF₃

F494 H H F CH₃ Br H 0 cyclopropyl

F495 H H F CH₃ CI H 0 cyclopropyl

F496 H H F CH₃ CF₃ H 0 cyclopropyl

F497 H H F CH₃ CH₃ H 0 cyclopropyl F498 H H F CH₃ Br H 0 CH₂CH₃

F499 H H F CH₃ CI H 0 CH₂CH₃

F500 H H F CH₃ CF₃ H 0 CH₂CH₃

F501 H H F CH₃ CH₃ H 0 CH₂CH₃

F502 H H F CH₃ Br H s CH₂CH₃

F503 H H F CH₃ CI H s CH₂CH₃

F504 H H F CH₃ CF₃ H s CH₂CH₃

F505 H H F CH₃ CH₃ H s CH₂CH₃

F506 H H F CH₃ Br CH₃ s CH₂CH₃

F507 H H F CH₃ CI CH₃ s CH₂CH₃

F508 H H F CH₃ CF₃ CH₃ s CH₂CH₃

F509 H H F CH₃ CH₃ CH₃ s CH₂CH₃

F510 H H F CH₃ Br CH₃ 0 CH₂CH₃

F511 H H F CH₃ CI CH₃ 0 CH₂CH₃

F512 H H F CH₃ CF₃ CH₃ 0 CH₂CH₃

F513 H H F CH₃ CH₃ CH₃ 0 CH₂CH₃

F514 H H F CH₃ Br CH₃ 0 CH₂CN

F515 H H F CH₃ CI CH₃ 0 CH₂CN

F516 H H F CH₃ CF₃ CH₃ 0 CH₂CN

F517 H H F CH₃ CH₃ CH₃ 0 CH₂CN

F518 H H F CH₃ Br CH₃ s cyclopropyl

F519 H H F CH₃ CI CH₃ s cyclopropyl

F520 H H F CH₃ CF₃ CH₃ s cyclopropyl

F521 H H F CH₃ CH₃ CH₃ s cyclopropyl

F522 H H F CI Br H 0 CH₂CF₃

F523 H H F CI CI H 0 CH₂CF₃ F524 H H F CI CF₃ H 0 CH₂CF₃

F525 H H F CI CH₃ H 0 CH₂CF₃

F526 H H F CI Br H 0 cyclopropyl

F527 H H F CI CI H 0 cyclopropyl

F528 H H F CI CF₃ H 0 cyclopropyl

F529 H H F CI CH₃ H 0 cyclopropyl

F530 H H F CI Br H 0 CH₂CH₃

F531 H H F CI CI H 0 CH₂CH₃

F532 H H F CI CF₃ H 0 CH₂CH₃

F533 H H F CI CH₃ H 0 CH₂CH₃

F534 H H F CI Br H s CH₂CH₃

F535 H H F CI CI H s CH₂CH₃

F536 H H F CI CF₃ H s CH₂CH₃

F537 H H F CI CH₃ H s CH₂CH₃

F538 H H F CI Br CH₃ s CH₂CH₃

F539 H H F CI CI CH₃ s CH₂CH₃

F540 H H F CI CF₃ CH₃ s CH₂CH₃

F541 H H F CI CH₃ CH₃ s CH₂CH₃

F542 H H F CI Br CH₃ 0 CH₂CH₃

F543 H H F CI CI CH₃ 0 CH₂CH₃

F544 H H F CI CF₃ CH₃ 0 CH₂CH₃

F545 H H F CI CH₃ CH₃ 0 CH₂CH₃

F546 H H F CI Br CH₃ 0 CH₂CN

F547 H H F CI CI CH₃ 0 CH₂CN

F548 H H F CI CF₃ CH₃ 0 CH₂CN

F549 H H F CI CH₃ CH₃ 0 CH₂CN F550 H H F CI Br CH₃ S cyclopropyl

F551 H H F CI CI CH₃ s cyclopropyl

F552 H H F CI CF₃ CH₃ s cyclopropyl

F553 H H F CI CH₃ CH₃ s cyclopropyl

F554 H F F F Br H 0 CH₂CF₃

F555 H F F F CI H 0 CH₂CF₃

F556 H F F F CF₃ H 0 CH₂CF₃

F557 H F F F CH₃ H 0 CH₂CF₃

F558 H F F F Br H 0 cyclopropyl

F559 H F F F CI H 0 cyclopropyl

F560 H F F F CF₃ H 0 cyclopropyl

F561 H F F F CH₃ H 0 cyclopropyl

F562 H F F F Br H 0 CH₂CH₃

F563 H F F F CI H 0 CH₂CH₃

F564 H F F F CF₃ H 0 CH₂CH₃

F565 H F F F CH₃ H 0 CH₂CH₃

F566 H F F F Br H s CH₂CH₃

F567 H F F F CI H s CH₂CH₃

F568 H F F F CF₃ H s CH₂CH₃

F569 H F F F CH₃ H s CH₂CH₃

F570 H F F F Br CH₃ s CH₂CH₃

F571 H F F F CI CH₃ s CH₂CH₃

F572 H F F F CF₃ CH₃ s CH₂CH₃

F573 H F F F CH₃ CH₃ s CH₂CH₃

F574 H F F F Br CH₃ 0 CH₂CH₃

F575 H F F F CI CH₃ 0 CH₂CH₃ F576 H F F F CF₃ CH₃ 0 CH₂CH₃

F577 H F F F CH₃ CH₃ 0 CH₂CH₃

F578 H F F F Br CH₃ 0 CH₂CN

F579 H F F F CI CH₃ 0 CH₂CN

F580 H F F F CF₃ CH₃ 0 CH₂CN

F581 H F F F CH₃ CH₃ 0 CH₂CN

F582 H F F F Br CH₃ S cyclopropyl

F583 H F F F CI CH₃ s cyclopropyl

F584 H F F F CF₃ CH₃ s cyclopropyl

F585 H F F F CH₃ CH₃ s cyclopropyl

F586 H CF₃ H CF₃ Br H 0 CH₂CF₃

F587 H CF₃ H CF₃ CI H 0 CH₂CF₃

F588 H CF₃ H CF₃ CF₃ H 0 CH₂CF₃

F589 H CF₃ H CF₃ CH₃ H 0 CH₂CF₃

F590 H CF₃ H CF₃ Br H 0 cyclopropyl

F591 H CF₃ H CF₃ CI H 0 cyclopropyl

F592 H CF₃ H CF₃ CF₃ H 0 cyclopropyl

F593 H CF₃ H CF₃ CH₃ H 0 cyclopropyl

F594 H CF₃ H CF₃ Br H 0 CH₂CH₃

F595 H CF₃ H CF₃ CI H 0 CH₂CH₃

F596 H CF₃ H CF₃ CF₃ H 0 CH₂CH₃

F597 H CF₃ H CF₃ CH₃ H 0 CH₂CH₃

F598 H CF₃ H CF₃ Br H s CH₂CH₃

F599 H CF₃ H CF₃ CI H s CH₂CH₃

F600 H CF₃ H CF₃ CF₃ H s CH₂CH₃

F601 H CF₃ H CF₃ CH₃ H s CH₂CH₃ F602 H CF₃ H CF₃ Br CH₃ S CH₂CH₃

F603 H CF₃ H CF₃ CI CH₃ S CH₂CH₃

F604 H CF₃ H CF₃ CF₃ CH₃ s CH₂CH₃

F605 H CF₃ H CF₃ CH₃ CH₃ s CH₂CH₃

F606 H CF₃ H CF₃ Br CH₃ 0 CH₂CH₃

F607 H CF₃ H CF₃ CI CH₃ 0 CH₂CH₃

F608 H CF₃ H CF₃ CF₃ CH₃ 0 CH₂CH₃

F609 H CF₃ H CF₃ CH₃ CH₃ 0 CH₂CH₃

F610 H CF₃ H CF₃ Br CH₃ 0 CH₂CN

F611 H CF₃ H CF₃ CI CH₃ 0 CH₂CN

F612 H CF₃ H CF₃ CF₃ CH₃ 0 CH₂CN

F613 H CF₃ H CF₃ CH₃ CH₃ 0 CH₂CN

F614 H CF₃ H CF₃ Br CH₃ s cyclopropyl

F615 H CF₃ H CF₃ CI CH₃ s cyclopropyl

F616 H CF₃ H CF₃ CF₃ CH₃ s cyclopropyl

F617 H CF₃ H CF₃ CH₃ CH₃ s cyclopropyl

F618 H F H CF₃ Br H 0 CH₂CF₃

F619 H F H CF₃ CI H 0 CH₂CF₃

F620 H F H CF₃ CF₃ H 0 CH₂CF₃

F621 H F H CF₃ CH₃ H 0 CH₂CF₃

F622 H F H CF₃ Br H 0 cyclopropyl

F623 H F H CF₃ CI H 0 cyclopropyl

F624 H F H CF₃ CF₃ H 0 cyclopropyl

F625 H F H CF₃ CH₃ H 0 cyclopropyl

F626 H F H CF₃ Br H 0 CH₂CH₃

F627 H F H CF₃ CI H 0 CH₂CH₃ F628 H F H CF₃ CF₃ H 0 CH₂CH₃

F629 H F H CF₃ CH₃ H 0 CH₂CH₃

F630 H F H CF₃ Br H S CH₂CH₃

F631 H F H CF₃ CI H s CH₂CH₃

F632 H F H CF₃ CF₃ H s CH₂CH₃

F633 H F H CF₃ CH₃ H s CH₂CH₃

F634 H F H CF₃ Br CH₃ s CH₂CH₃

F635 H F H CF₃ CI CH₃ s CH₂CH₃

F636 H F H CF₃ CF₃ CH₃ s CH₂CH₃

F637 H F H CF₃ CH₃ CH₃ s CH₂CH₃

F638 H F H CF₃ Br CH₃ 0 CH₂CH₃

F639 H F H CF₃ CI CH₃ 0 CH₂CH₃

F640 H F H CF₃ CF₃ CH₃ 0 CH₂CH₃

F641 H F H CF₃ CH₃ CH₃ 0 CH₂CH₃

F642 H F H CF₃ Br CH₃ 0 CH₂CN

F643 H F H CF₃ CI CH₃ 0 CH₂CN

F644 H F H CF₃ CF₃ CH₃ 0 CH₂CN

F645 H F H CF₃ CH₃ CH₃ 0 CH₂CN

F646 H F H CF₃ Br CH₃ s cyclopropyl

F647 H F H CF₃ CI CH₃ s cyclopropyl

F648 H F H CF₃ CF₃ CH₃ s cyclopropyl

F649 H F H CF₃ CH₃ CH₃ s cyclopropyl

F650 H CI H CF₃ Br H 0 CH₂CF₃

F651 H CI H CF₃ CI H 0 CH₂CF₃

F652 H CI H CF₃ CF₃ H 0 CH₂CF₃

F653 H CI H CF₃ CH₃ H 0 CH₂CF₃ F654 H CI H CF₃ Br H 0 cyclopropyl

F655 H CI H CF₃ CI H 0 cyclopropyl

F656 H CI H CF₃ CF₃ H 0 cyclopropyl

F657 H CI H CF₃ CH₃ H 0 cyclopropyl

F658 H CI H CF₃ Br H 0 CH₂CH₃

F659 H CI H CF₃ CI H 0 CH₂CH₃

F660 H CI H CF₃ CF₃ H 0 CH₂CH₃

F661 H CI H CF₃ CH₃ H 0 CH₂CH₃

F662 H CI H CF₃ Br H s CH₂CH₃

F663 H CI H CF₃ CI H s CH₂CH₃

F664 H CI H CF₃ CF₃ H s CH₂CH₃

F665 H CI H CF₃ CH₃ H s CH₂CH₃

F666 H CI H CF₃ Br CH₃ s CH₂CH₃

F667 H CI H CF₃ CI CH₃ s CH₂CH₃

F668 H CI H CF₃ CF₃ CH₃ s CH₂CH₃

F669 H CI H CF₃ CH₃ CH₃ s CH₂CH₃

F670 H CI H CF₃ Br CH₃ 0 CH₂CH₃

F671 H CI H CF₃ CI CH₃ 0 CH₂CH₃

F672 H CI H CF₃ CF₃ CH₃ 0 CH₂CH₃

F673 H CI H CF₃ CH₃ CH₃ 0 CH₂CH₃

F674 H CI H CF₃ Br CH₃ 0 CH₂CN

F675 H CI H CF₃ CI CH₃ 0 CH₂CN

F676 H CI H CF₃ CF₃ CH₃ 0 CH₂CN

F677 H CI H CF₃ CH₃ CH₃ 0 CH₂CN

F678 H CI H CF₃ Br CH₃ s cyclopropyl

F679 H CI H CF₃ CI CH₃ s cyclopropyl F680 H CI H CF₃ CF₃ CH₃ S cyclopropyl

F681 H CI H CF₃ CH₃ CH₃ s cyclopropyl

F682 H H F CF₃ Br H 0 CH₂CF₃

F683 H H F CF₃ CI H 0 CH₂CF₃

F684 H H F CF₃ CF₃ H 0 CH₂CF₃

F685 H H F CF₃ CH₃ H 0 CH₂CF₃

F686 H H F CF₃ Br H 0 cyclopropyl

F687 H H F CF₃ CI H 0 cyclopropyl

F688 H H F CF₃ CF₃ H 0 cyclopropyl

F689 H H F CF₃ CH₃ H 0 cyclopropyl

F690 H H F CF₃ Br H 0 CH₂CH₃

F691 H H F CF₃ CI H 0 CH₂CH₃

F692 H H F CF₃ CF₃ H 0 CH₂CH₃

F693 H H F CF₃ CH₃ H 0 CH₂CH₃

F694 H H F CF₃ Br H s CH₂CH₃

F695 H H F CF₃ CI H s CH₂CH₃

F696 H H F CF₃ CF₃ H s CH₂CH₃

F697 H H F CF₃ CH₃ H s CH₂CH₃

F698 H H F CF₃ Br CH₃ s CH₂CH₃

F699 H H F CF₃ CI CH₃ s CH₂CH₃

F700 H H F CF₃ CF₃ CH₃ s CH₂CH₃

F701 H H F CF₃ CH₃ CH₃ s CH₂CH₃

F702 H H F CF₃ Br CH₃ 0 CH₂CH₃

F703 H H F CF₃ CI CH₃ 0 CH₂CH₃

F704 H H F CF₃ CF₃ CH₃ 0 CH₂CH₃

F705 H H F CF₃ CH₃ CH₃ 0 CH₂CH₃ F706 H H F CF₃ Br CH₃ 0 CH₂CN

F707 H H F CF₃ CI CH₃ 0 CH₂CN

F708 H H F CF₃ CF₃ CH₃ 0 CH₂CN

F709 H H F CF₃ CH₃ CH₃ 0 CH₂CN

F710 H H F CF₃ Br CH₃ S cyclopropyl

F711 H H F CF₃ CI CH₃ s cyclopropyl

F712 H H F CF₃ CF₃ CH₃ s cyclopropyl

F713 H H F CF₃ CH₃ CH₃ s cyclopropyl

F714 H CI CI CI CI H 0 cyclopropyl

F715 H CI CI CI CF₃ H 0 cyclopropyl

F716 H CI CI CI CH₃ H 0 cyclopropyl

F717 H CI CI CI CI H 0 CH₂CH₃

F718 H CI CI CI CF₃ H 0 CH₂CH₃

F719 H CI CI CI CH₃ H 0 CH₂CH₃

F720 H CI CI CI CI H s CH₂CH₃

F721 H CI CI CI CF₃ H s CH₂CH₃

F722 H CI CI CI CH₃ H s CH₂CH₃

F723 H CI CI CI CI CH₃ s CH₂CH₃

F724 H CI CI CI CF₃ CH₃ s CH₂CH₃

F725 H CI CI CI CH₃ CH₃ s CH₂CH₃

F726 H CI CI CI CI CH₃ 0 CH₂CH₃

F727 H CI CI CI CF₃ CH₃ 0 CH₂CH₃

F728 H CI CI CI CH₃ CH₃ 0 CH₂CH₃

F729 H CI CI CI CI CH₃ 0 CH₂CN

F730 H CI CI CI CF₃ CH₃ 0 CH₂CN

F731 H CI CI CI CH₃ CH₃ 0 CH₂CN F732 H CI CI CI CI CH₃ S cyclopropyl

F733 H CI CI CI CF₃ CH₃ s cyclopropyl

F734 H CI CI CI CH₃ CH₃ s cyclopropyl

F735 H CI H CI Br H 0 CH₂CF₃

F736 H CI H CI CI H 0 CH₂CF₃

F737 H CI H CI CF₃ H 0 CH₂CF₃

F738 H CI H CI CH₃ H 0 CH₂CF₃

F739 H CI H CI Br H 0 cyclopropyl

F740 H CI H CI CI H 0 cyclopropyl

F741 H CI H CI CF₃ H 0 cyclopropyl

F742 H CI H CI CH₃ H 0 cyclopropyl

F743 H CI H CI Br H 0 CH₂CH₃

F744 H CI H CI CI H 0 CH₂CH₃

F745 H CI H CI CF₃ H 0 CH₂CH₃

F746 H CI H CI CH₃ H 0 CH₂CH₃

F747 H CI H CI Br H s CH₂CH₃

F748 H CI H CI CI H s CH₂CH₃

F749 H CI H CI CF₃ H s CH₂CH₃

F750 H CI H CI CH₃ H s CH₂CH₃

F751 H CI H CI Br CH₃ s CH₂CH₃

F752 H CI H CI CI CH₃ s CH₂CH₃

F753 H CI H CI CF₃ CH₃ s CH₂CH₃

F754 H CI H CI CH₃ CH₃ s CH₂CH₃

F755 H CI H CI Br CH₃ 0 CH₂CH₃

F756 H CI H CI CI CH₃ 0 CH₂CH₃

F757 H CI H CI CF₃ CH₃ 0 CH₂CH₃ F758 H CI H CI CH₃ CH₃ 0 CH₂CH₃

F759 H CI H CI Br CH₃ 0 CH₂CN

F760 H CI H CI CI CH₃ 0 CH₂CN

F761 H CI H CI CF₃ CH₃ 0 CH₂CN

F762 H CI H CI CH₃ CH₃ 0 CH₂CN

F763 H CI H CI Br CH₃ S cyclopropyl

F764 H CI H CI CI CH₃ s cyclopropyl

F765 H CI H CI CF₃ CH₃ s cyclopropyl

F766 H CI H CI CH₃ CH₃ s cyclopropyl

F767 H H CI CI Br H 0 CH₂CF₃

F768 H H CI CI CI H 0 CH₂CF₃

F769 H H CI CI CF₃ H 0 CH₂CF₃

F770 H H CI CI CH₃ H 0 CH₂CF₃

F771 H H CI CI Br H 0 cyclopropyl

F772 H H CI CI CI H 0 cyclopropyl

F773 H H CI CI CF₃ H 0 cyclopropyl

F774 H H CI CI CH₃ H 0 cyclopropyl

F775 H H CI CI Br H 0 CH₂CH₃

F776 H H CI CI CI H 0 CH₂CH₃

F777 H H CI CI CF₃ H 0 CH₂CH₃

F778 H H CI CI CH₃ H 0 CH₂CH₃

F779 H H CI CI Br H s CH₂CH₃

F780 H H CI CI CI H s CH₂CH₃

F781 H H CI CI CF₃ H s CH₂CH₃

F782 H H CI CI CH₃ H s CH₂CH₃

F783 H H CI CI Br CH₃ s CH₂CH₃ F784 H H CI CI CI CH₃ S CH₂CH₃

F785 H H CI CI CF₃ CH₃ S CH₂CH₃

F786 H H CI CI CH₃ CH₃ s CH₂CH₃

F787 H H CI CI Br CH₃ 0 CH₂CH₃

F788 H H CI CI CI CH₃ 0 CH₂CH₃

F789 H H CI CI CF₃ CH₃ 0 CH₂CH₃

F790 H H CI CI CH₃ CH₃ 0 CH₂CH₃

F791 H H CI CI Br CH₃ 0 CH₂CN

F792 H H CI CI CI CH₃ 0 CH₂CN

F793 H H CI CI CF₃ CH₃ 0 CH₂CN

F794 H H CI CI CH₃ CH₃ 0 CH₂CN

F795 H H CI CI Br CH₃ s cyclopropyl

F796 H H CI CI CI CH₃ s cyclopropyl

F797 H H CI CI CF₃ CH₃ s cyclopropyl

F798 H H CI CI CH₃ CH₃ s cyclopropyl

F799 H CI F CI CI H 0 CH₂CF₃

F800 H CI F CI CF₃ H 0 CH₂CF₃

F801 H CI F CI CH₃ H 0 CH₂CF₃

F802 H CI F CI Br H 0 cyclopropyl

F803 H CI F CI CI H 0 cyclopropyl

F804 H CI F CI CF₃ H 0 cyclopropyl

F805 H CI F CI CH₃ H 0 cyclopropyl

F806 H CI F CI Br H 0 CH₂CH₃

F807 H CI F CI CI H 0 CH₂CH₃

F808 H CI F CI CF₃ H 0 CH₂CH₃

F809 H CI F CI CH₃ H 0 CH₂CH₃ F810 H CI F CI Br H S CH₂CH₃

F811 H CI F CI CI H S CH₂CH₃

F812 H CI F CI CF₃ H s CH₂CH₃

F813 H CI F CI CH₃ H s CH₂CH₃

F814 H CI F CI Br CH₃ s CH₂CH₃

F815 H CI F CI CI CH₃ s CH₂CH₃

F816 H CI F CI CF₃ CH₃ s CH₂CH₃

F817 H CI F CI CH₃ CH₃ s CH₂CH₃

F818 H CI F CI Br CH₃ 0 CH₂CH₃

F819 H CI F CI CI CH₃ 0 CH₂CH₃

F820 H CI F CI CF₃ CH₃ 0 CH₂CH₃

F821 H CI F CI CH₃ CH₃ 0 CH₂CH₃

F822 H CI F CI Br CH₃ 0 CH₂CN

F823 H CI F CI CI CH₃ 0 CH₂CN

F824 H CI F CI CF₃ CH₃ 0 CH₂CN

F825 H CI F CI CH₃ CH₃ 0 CH₂CN

F826 H CI F CI Br CH₃ s cyclopropyl

F827 H CI F CI CI CH₃ s cyclopropyl

F828 H CI F CI CF₃ CH₃ s cyclopropyl

F829 H CI F CI CH₃ CH₃ s cyclopropyl

F830 H Br H Br CI H 0 CH₂CF₃

F831 H Br H Br CF₃ H 0 CH₂CF₃

F832 H Br H Br CH₃ H 0 CH₂CF₃

F833 H Br H Br Br H 0 cyclopropyl

F834 H Br H Br CI H 0 cyclopropyl

F835 H Br H Br CF₃ H 0 cyclopropyl F836 H Br H Br CH₃ H 0 cyclopropyl

F837 H Br H Br Br H 0 CH₂CH₃

F838 H Br H Br CI H 0 CH₂CH₃

F839 H Br H Br CF₃ H 0 CH₂CH₃

F840 H Br H Br CH₃ H 0 CH₂CH₃

F841 H Br H Br Br H s CH₂CH₃

F842 H Br H Br CI H s CH₂CH₃

F843 H Br H Br CF₃ H s CH₂CH₃

F844 H Br H Br CH₃ H s CH₂CH₃

F845 H Br H Br Br CH₃ s CH₂CH₃

F846 H Br H Br CI CH₃ s CH₂CH₃

F847 H Br H Br CF₃ CH₃ s CH₂CH₃

F848 H Br H Br CH₃ CH₃ s CH₂CH₃

F849 H Br H Br Br CH₃ 0 CH₂CH₃

F850 H Br H Br CI CH₃ 0 CH₂CH₃

F851 H Br H Br CF₃ CH₃ 0 CH₂CH₃

F852 H Br H Br CH₃ CH₃ 0 CH₂CH₃

F853 H Br H Br Br CH₃ 0 CH₂CN

F854 H Br H Br CI CH₃ 0 CH₂CN

F855 H Br H Br CF₃ CH₃ 0 CH₂CN

F856 H Br H Br CH₃ CH₃ 0 CH₂CN

F857 H Br H Br Br CH₃ s cyclopropyl

F858 H Br H Br CI CH₃ s cyclopropyl

F859 H Br H Br CF₃ CH₃ s cyclopropyl

F860 H Br H Br CH₃ CH₃ s cyclopropyl Example A: Bio ASSAYS ON BEET ARMYWORM ("BAW") AND CORN EARWORM ("CEW") AND CABBAGE LOOPER ("CL")

BAW has few effective parasites, diseases, or predators to lower its population. BAW infests many weeds, trees, grasses, legumes, and field crops. In various places, it is of economic concern upon asparagus, cotton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers, tomatoes, potatoes, onions, peas, sunflowers, and citrus, among other plants. CEW is known to attack corn and tomatoes, but it also attacks artichoke, asparagus, cabbage, cantaloupe, collards, cowpeas, cucumbers, eggplant, lettuce, lima beans, melon, okra, peas, peppers, potatoes, pumpkin, snap beans, spinach, squash, sweet potatoes, and watermelon, among other plants. CEW is also known to be resistant to certain insecticides. CL feeds on a wide variety of cultivated plants and weeds. It feeds readily on crucifers, and has been reported damaging broccoli, cabbage, cauliflower, Chinese cabbage, collards, kale, mustard, radish, rutabaga, turnip, and watercress. Other vegetable crops injured include beet, cantaloupe, celery, cucumber, lima bean, lettuce, parsnip, pea, pepper, potato, snap bean, spinach, squash, sweet potato, tomato, and watermelon. CL is also known to be resistant to certain insecticides. Consequently, because of the above factors control of these pests is important. Furthermore, molecules that control these pests are useful in controlling other pests.

Certain molecules disclosed in this document were tested against BAW and CEW and CL using procedures described in the following examples. In the reporting of the results, the "BAW & CEW & CL Rating Table" was used (See Table Section).

BiOASSAYS ON BAW (Spodoptera exigua)

Bioassays on BAW were conducted using a 128-well diet tray assay, one to five second instar BAW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg/cm² of the test compound

(dissolved in 50 μL· of 90: 10 acetone- water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25 °C, 14: 10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled "Table 3: Assay Results" (See Table Section).

BIOASSAYS ON CEW (Helicoverpa zed)

Bioassays on CEW were conducted using a 128-well diet tray assay, one to five second instar CEW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg /cm² of the test compound (dissolved in 50 μL· of 90: 10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25 °C, 14: 10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled "Table 3: Assay Results" (See Table Section).

Bioassays on CL (Trichoplusia ni)

Bioassays on CL were conducted using a 128-well diet tray assay. One to five second instar CL larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 μg /cm² of the test compound (dissolved in 50 μL· of 90: 10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover, and held at 25 °C, 14: 10 light-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled "Table 3A: Assay Results" (See Table Section).

Example B: BIOASSAYS ON GREEN PEACH APHID ("GPA") {Myzus persicae).

GPA is the most significant aphid pest of peach trees, causing decreased growth, shriveling of the leaves, and the death of various tissues. It is also hazardous because it acts as a vector for the transport of plant viruses, such as potato virus Y and potato leafroll virus to members of the nightshade/potato family Solanaceae, and various mosaic viruses to many other food crops. GPA attacks such plants as broccoli, burdock, cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many ornamental crops such as carnation, chrysanthemum, flowering white cabbage, poinsettia, and roses. GPA has developed resistance to many pesticides.

Certain molecules disclosed in this document were tested against GPA using procedures described in the following example. In the reporting of the results, the "GPA Rating Table" was used (See Table Section).

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) true leaves, were used as test substrate. The seedlings were infested with 20-50 GPA (wingless adult and nymph stages) one day prior to chemical application. Four pots with individual seedlings were used for each treatment. Test compounds (2 mg) were dissolved in 2 mL of

acetone/MeOH (1: 1) solvent, forming stock solutions of 1000 ppm test compound. The stock solutions were diluted 5X with 0.025% Tween 20 in water to obtain the solution at 200 ppm test compound. A hand-held aspirator-type sprayer was used for spraying a solution to both sides of cabbage leaves until runoff. Reference plants (solvent check) were sprayed with the diluent only containing 20% by volume of acetone/MeOH (1:1) solvent. Treated plants were held in a holding room for three days at approximately 25 °C and ambient relative humidity (RH) prior to grading. Evaluation was conducted by counting the number of live aphids per plant under a microscope. Percent Control was measured by using Abbott's correction formula (W.S. Abbott, "A Method of Computing the Effectiveness of an Insecticide" J. Econ. Entomol. 18 (1925), pp.265-267) as follows.

Corrected % Control = 100 * (X - Y) / X

where

X = No. of live aphids on solvent check plants and

Y = No. of live aphids on treated plants

The results are indicated in the table entitled "Table 3: Assay Results" (See Table Section).

PESTICIDALLY ACCEPTABLE ACID ADDITION SALTS, SALT DERIVATIVES, SOLVATES, ESTER DERIVATIVES, POLYMORPHS, ISOTOPES AND

RADIONUCLIDES

Molecules of Formula One may be formulated into pesticidally acceptable acid addition salts. By way of a non-limiting example, an amine function can form salts with hydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, lactic, gluconic, ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and

hydroxyethanesulfonic acids. Additionally, by way of a non-limiting example, an acid function can form salts including those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Examples of preferred cations include sodium, potassium, and magnesium.

Molecules of Formula One may be formulated into salt derivatives. By way of a non- limiting example, a salt derivative can be prepared by contacting a free base with a sufficient amount of the desired acid to produce a salt. A free base may be regenerated by treating the salt with a suitable dilute aqueous base solution such as dilute aqueous sodium hydroxide (NaOH), potassium carbonate, ammonia, and sodium bicarbonate. As an example, in many cases, a pesticide, such as 2,4-D, is made more water-soluble by converting it to its dimethylamine salt..

Molecules of Formula One may be formulated into stable complexes with a solvent, such that the complex remains intact after the non-complexed solvent is removed. These complexes are often referred to as "solvates." However, it is particularly desirable to form stable hydrates with water as the solvent.

Molecules of Formula One may be made into ester derivatives. These ester derivatives can then be applied in the same manner as the invention disclosed in this document is applied.

Molecules of Formula One may be made as various crystal polymorphs.

Polymorphism is important in the development of agrochemicals since different crystal polymorphs or structures of the same molecule can have vastly different physical properties and biological performances.

Molecules of Formula One may be made with different isotopes. Of particular importance are molecules having ²H (also known as deuterium) in place of ^]Η.

Molecules of Formula One may be made with different radionuclides. Of particular importance are molecules having ¹⁴C.

STEREOISOMERS

Molecules of Formula One may exist as one or more stereoisomers. Thus, certain molecules can be produced as racemic mixtures. It will be appreciated by those skilled in the art that one stereoisomer may be more active than the other stereoisomers. Individual stereoisomers may be obtained by known selective synthetic procedures, by conventional synthetic procedures using resolved starting materials, or by conventional resolution procedures. Certain molecules disclosed in this document can exist as two or more isomers. The various isomers include geometric isomers, diastereomers, and enantiomers. Thus, the molecules disclosed in this document include geometric isomers, racemic mixtures, individual stereoisomers, and optically active mixtures. It will be appreciated by those skilled in the art that one isomer may be more active than the others. The structures disclosed in the present disclosure are drawn in only one geometric form for clarity, but are intended to represent all geometric forms of the molecule.

COMBINATIONS

Molecules of Formula One may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal, or virucidal properties. Additionally, the molecules of Formula One may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with compounds that are antifeedants, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, plant activators, plant growth regulators, or synergists. Examples of such compounds in the above groups that may be used with the Molecules of Formula One are - (3-ethoxypropyl)mercury bromide, 1 ,2-dichloropropane, 1,3- dichloropropene, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri- iodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6- TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5- T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T- sodium, 2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D- 2-ethylhexyl, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB- dimethylammonium, 2,4-DB-isoctyl, 2,4-DB -potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4- D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D- dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D- isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D- meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D- sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2- hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2- phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA- sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8 -hydroxy quinoline sulfate, 8- phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl, acifluorf en- sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, alloxydim-sodium, allyl alcohol, allyxycarb, alorac, α/ρΛα-cypermethrin, α/ρ/ζα-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2- hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium a-naphthaleneacetate, amobam, ampropylfos, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam, asulam-potassium, asulam- sodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphos- methyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin- ethyl, benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone- sodium, benthiavalicarb, benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox, benzadox- ammonium, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid, benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl benzoate,

benzyladenine, berberine, berberine chloride, ^eta-cyfluthrin, ^eto-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bispyribac-sodium, bistrifluron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium,

brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin, butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chloramben-methylammonium, chloramben-sodium, chloramine phosphorus, chloramphenicol, chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac, chlorfenac- ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlornidine, chlornitrofen, chlorobenzilate, chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin, chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron, chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim, chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos, chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2- hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, cloransulam- methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA, codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide, cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron, cycloxaprid, cycloxydim, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon- sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DBCP, J-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton- O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton- S-methylsulphon, desmedipham, desmetryn, J-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos, diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba-diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba- isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba- sodium, dicamba-trolamine, dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop-ethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2-ethylhexyl, dichlorprop-P- dimethylammonium, dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum,

difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate, dimethyl phthalate,

dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquat dibromide, disparlure, disul, disulfiram, disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron, d- limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothal-diammonium, endothal- dipotassium, endothal-disodium, endothion, endrin, enestroburin, EPN, epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan, esdepallethrine, esfenvalerate, esprocarb, etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen, ethoxyfen- ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl a-naphthaleneacetate, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etinofen, etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos, fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl,

fenchlorphos, fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl, fenoprop- butometyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop- potassium, fenothiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine, fenpyroximate, fenridazon, fenridazon- potassium, fenridazon-propyl, fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop- ethyl, fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M- isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop- P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl, flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid, fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate, flupropanate-sodium, flupyradifurone, flupyrsulfuron, flupyrsulfuron-methyl, flupyrsulfuron- methyl-sodium, fluquinconazole, flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl,

flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl, fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCR, genit, gibberellic acid, gibberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammonium, glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium, glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acetates, halacrinate, halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop- methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox- ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium, imazaquin-methyl, imazaquin- sodium, imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane, iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron,

iofensulfuron-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin, isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron, isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kadethrin, karbutilate, karetazan, karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim- methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron, lvdingjunzhi, lvxiancaolin, lythidathion, MAA, malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA, MCPA- 2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA- olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB-methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2- ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium, mecoprop-P-potassium, mecoprop- sodium, mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide,

methylneodecanamide, metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin, N-(ethylmercury)-p- toluenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin, neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine, nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide, norflurazon, nomicotine, noruron, novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene,

orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxine-copper, oxolinic acid,

oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, para-dichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride,

phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram- methyl, picloram-olamine, picloram-potassium, picloram-triethylammonium, picloram-tris(2- hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone- sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl, pirimiphos- methyl, plifenate, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium a-naphthaleneacetate, ρρ'-ΌΌΎ, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione, prohexadione- calcium, prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit, propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, propiconazole, propineb, propisochlor, propoxur, propoxycarbazone,

propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute, proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac- sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P- tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium a-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep, toi/-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA- calcium, TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton,

terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon, tetrafluron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultap- monosodium, thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil, tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad, tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim, tralocythrin, tralomethrin, tralopyril, transfluthrin,

transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamone, tri-allate, triamiphos, triapenthenol, triarathene, triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop- methyl, trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium, warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, a-chlorohydrin, a-ecdysone, a-multistriatin, and a-naphthaleneacetic acid. For more information consult the "COMPENDIUM OF PESTICIDE COMMON NAMES" located at http://www.alanwood.net/pesticides/index.html. Also consult "THE PESTICIDE MANUAL" 14th Edition, edited by C D S Tomlin, copyright 2006 by British Crop Production Council, or its prior or more recent editions.

BIOPESTICIDES

Molecules of Formula One may also be used in combination (such as in a

compositional mixture, or a simultaneous or sequential application) with one or more biopesticides. The term "biopesticide" is used for microbial biological pest control agents that are applied in a similar manner to chemical pesticides. Commonly these are bacterial, but there are also examples of fungal control agents, including Trichoderma spp. and

Ampelomyces quisqualis (a control agent for grape powdery mildew). Bacillus subtilis are used to control plant pathogens. Weeds and rodents have also been controlled with microbial agents. One well-known insecticide example is Bacillus thuringiensis, a bacterial disease of Lepidoptera, Coleoptera, and Diptera. Because it has little effect on other organisms, it is considered more environmentally friendly than synthetic pesticides. Biological insecticides include products based on:

1. entomopathogenic fungi {e.g. Metarhizium anisopliae);

2. entomopathogenic nematodes (e.g. Steinernema feltiae); and

3. entomopathogenic viruses (e.g. Cydia pomonella granulo virus).

Other examples of entomopathogenic organisms include, but are not limited to, baculoviruses, bacteria and other prokaryotic organisms, fungi, protozoa and Microsproridia. Biologically derived insecticides include, but not limited to, rotenone, veratridine, as well as microbial toxins; insect tolerant or resistant plant varieties; and organisms modified by recombinant DNA technology to either produce insecticides or to convey an insect resistant property to the genetically modified organism. In one embodiment, the molecules of Formula One may be used with one or more biopesticides in the area of seed treatments and soil amendments. The Manual of Biocontrol Agents gives a review of the available biological insecticide (and other biology -based control) products. Copping L.G. (ed.) (2004). The Manual of Biocontrol Agents (formerly the Biopesticide Manual) 3rd Edition. British Crop Production Council (BCPC), Farnham, Surrey UK.

OTHER ACTIVE COMPOUNDS

Molecules of Formula One may also be used in combination (such as in a

compositional mixture, or a simultaneous or sequential application) with one or more of the following:

1. 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-l-azaspiro[4,5]dec-3-en-2-one;

2. 3-(4'-chloro-2,4-dimethyl[l,l '-biphenyl]-3-yl)-4-hydroxy-8-oxa-l-azaspiro[4,5]dec- 3-en-2-one;

3. 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone;

4. 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone;

5. 3-chloro-N2-[(15')-l-methyl-2-(methylsulfonyl)ethyl]-Nl-[2-methyl-4-[l,2,2,2- tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl]- 1 ,2-benzenedicarboxamide;

6. 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide;

7. 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide;

8. 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide;

9. 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide;

10. 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide;

11. 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide;

12. 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide;

13. 3 -(difluoromethyl)-N- [2-(3 ,3-dimethylbutyl)phenyl] - 1 -methyl- lH-pyrazole-4- carboxamide;

14. N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-a,a,a-trifluoro-/?-tolyl) hydrazone;

15. N-ethyl-2,2-dichloro-l-methylcyclopropane-carboxamide-2-(2,6-dichloro-a,a,a- trifluoro-/?-tolyl) hydrazone nicotine;

16. 0-{(E-)-[2-(4-chloro-phenyl)-2-cyano-l-(2-trifluoromethylphenyl)-vinyl] } S-methyl thiocarbonate;

17. (E)-Nl-[(2-chloro-l,3-thiazol-5-ylmethyl)]-N2-cyano-Nl-methylacetamidine;

18. l-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro-l,2,3,5,6,7-hexahydro-imidazo[l,2- a]pyridin-5-ol;

19. 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate; and

20. N-Ethyl-2,2-dichloro-l-methylcyclopropanecarboxamide-2-(2,6-dichloro- alpha, alpha, a/p za-trifluoro-p-tolyl)hydrazone.

SYNERGISTIC MIXTURES Molecules of Formula One may be used with certain active compounds to form synergistic mixtures where the mode of action of such compounds compared to the mode of action of the molecules of Formula One are the same, similar, or different. Examples of modes of action include, but are not limited to: acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor; GABA and glutamate-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acetylcholine receptor agonist; acetylcholine receptor antagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acetylcholine receptor; Midgut membrane disrupter; oxidative phosphorylation disrupter, and ryanodine receptor (RyRs). Generally, weight ratios of the molecules of Formula One in a synergistic mixture with another compound are from about 10:1 to about 1:10, in another embodiment from about 5:1 to about 1:5, and in another embodiment from about 3:1, and in another embodiment about 1: 1.

FORMULATIONS

A pesticide is rarely suitable for application in its pure form. It is usually necessary to add other substances so that the pesticide can be used at the required concentration and in an appropriate form, permitting ease of application, handling, transportation, storage, and maximum pesticide activity. Thus, pesticides are formulated into, for example, baits, concentrated emulsions, dusts, emulsifiable concentrates, fumigants, gels, granules, microencapsulations, seed treatments, suspension concentrates, suspoemulsions, tablets, water soluble liquids, water dispersible granules or dry flowables, wettable powders, and ultra low volume solutions. For further information on formulation types see "Catalogue of Pesticide Formulation Types and International Coding System" Technical Monograph n°2, 5th Edition by CropLife International (2002).

Pesticides are applied most often as aqueous suspensions or emulsions prepared from concentrated formulations of such pesticides. Such water-soluble, water- suspendable, or emulsifiable formulations are either solids, usually known as wettable powders, or water dispersible granules, or liquids usually known as emulsifiable concentrates, or aqueous suspensions. Wettable powders, which may be compacted to form water dispersible granules, comprise an intimate mixture of the pesticide, a carrier, and surfactants. The concentration of the pesticide is usually from about 10% to about 90% by weight. The carrier is usually selected from among the attapulgite clays, the montmorillonite clays, the diatomaceous earths, or the purified silicates. Effective surfactants, comprising from about 0.5% to about 10% of the wettable powder, are found among sulfonated lignins, condensed naphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants such as ethylene oxide adducts of alkyl phenols.

Emulsifiable concentrates of pesticides comprise a convenient concentration of a pesticide, such as from about 50 to about 500 grams per liter of liquid dissolved in a carrier that is either a water miscible solvent or a mixture of water-immiscible organic solvent and emulsifiers. Useful organic solvents include aromatics, especially xylenes and petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitable emulsifiers for emulsifiable concentrates are selected from conventional anionic and non-ionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticides dispersed in an aqueous carrier at a concentration in the range from about 5% to about 50% by weight. Suspensions are prepared by finely grinding the pesticide and vigorously mixing it into a carrier comprised of water and surfactants. Ingredients, such as inorganic salts and synthetic or natural gums may also be added, to increase the density and viscosity of the aqueous carrier. It is often most effective to grind and mix the pesticide at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, ball mill, or piston-type homogenizer.

Pesticides may also be applied as granular compositions that are particularly useful for applications to the soil. Granular compositions usually contain from about 0.5% to about 10% by weight of the pesticide, dispersed in a carrier that comprises clay or a similar substance. Such compositions are usually prepared by dissolving the pesticide in a suitable solvent and applying it to a granular carrier which has been pre-formed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. Such compositions may also be formulated by making a dough or paste of the carrier and compound and crushing and drying to obtain the desired granular particle size.

Dusts containing a pesticide are prepared by intimately mixing the pesticide in powdered form with a suitable dusty agricultural carrier, such as kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1% to about 10% of the pesticide. They can be applied as a seed dressing or as a foliage application with a dust blower machine.

It is equally practical to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as the spray oils, which are widely used in agricultural chemistry. Pesticides can also be applied in the form of an aerosol composition. In such compositions the pesticide is dissolved or dispersed in a carrier, which is a pressure- generating propellant mixture. The aerosol composition is packaged in a container from which the mixture is dispensed through an atomizing valve.

Pesticide baits are formed when the pesticide is mixed with food or an attractant or both. When the pests eat the bait they also consume the pesticide. Baits may take the form of granules, gels, flowable powders, liquids, or solids. They can be used in pest harborages.

Fumigants are pesticides that have a relatively high vapor pressure and hence can exist as a gas in sufficient concentrations to kill pests in soil or enclosed spaces. The toxicity of the fumigant is proportional to its concentration and the exposure time. They are characterized by a good capacity for diffusion and act by penetrating the pest' s respiratory system or being absorbed through the pest' s cuticle. Fumigants are applied to control stored product pests under gas proof sheets, in gas sealed rooms or buildings or in special chambers.

Pesticides can be microencapsulated by suspending the pesticide particles or droplets in plastic polymers of various types. By altering the chemistry of the polymer or by changing factors in the processing, microcapsules can be formed of various sizes, solubility, wall thicknesses, and degrees of penetrability. These factors govern the speed with which the active ingredient within is released, which in turn, affects the residual performance, speed of action, and odor of the product.

Oil solution concentrates are made by dissolving pesticide in a solvent that will hold the pesticide in solution. Oil solutions of a pesticide usually provide faster knockdown and kill of pests than other formulations due to the solvents themselves having pesticidal action and the dissolution of the waxy covering of the integument increasing the speed of uptake of the pesticide. Other advantages of oil solutions include better storage stability, better penetration of crevices, and better adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, wherein the emulsion comprises oily globules which are each provided with a lamellar liquid crystal coating and are dispersed in an aqueous phase, wherein each oily globule comprises at least one compound which is agriculturally active, and is individually coated with a monolamellar or oligolamellar layer comprising: (1) at least one non-ionic lipophilic surface-active agent, (2) at least one non- ionic hydrophilic surface-active agent and (3) at least one ionic surface- active agent, wherein the globules having a mean particle diameter of less than 800 nanometers. Further information on the embodiment is disclosed in U.S. patent publication 20070027034 published February 1, 2007, having Patent Application serial number 11/495,228. For ease of use, this embodiment will be referred to as "OIWE".

For further information consult "Insect Pest Management" 2nd Edition by D. Dent, copyright CAB International (2000). Additionally, for more detailed information consult "Handbook of Pest Control - The Behavior, Life History, and Control of Household Pests" by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.

OTHER FORMULATION COMPONENTS

Generally, when the molecules disclosed in Formula One are used in a formulation, such formulation can also contain other components. These components include, but are not limited to, (this is a non-exhaustive and non-mutually exclusive list) wetters, spreaders, stickers, penetrants, buffers, sequestering agents, drift reduction agents, compatibility agents, anti-foam agents, cleaning agents, and emulsifiers. A few components are described forthwith.

A wetting agent is a substance that when added to a liquid increases the spreading or penetration power of the liquid by reducing the interfacial tension between the liquid and the surface on which it is spreading. Wetting agents are used for two main functions in agrochemical formulations: during processing and manufacture to increase the rate of wetting of powders in water to make concentrates for soluble liquids or suspension concentrates; and during mixing of a product with water in a spray tank to reduce the wetting time of wettable powders and to improve the penetration of water into water-dispersible granules. Examples of wetting agents used in wettable powder, suspension concentrate, and water-dispersible granule formulations are: sodium lauryl sulfate; sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphatic alcohol ethoxylates.

A dispersing agent is a substance which adsorbs onto the surface of particles and helps to preserve the state of dispersion of the particles and prevents them from

reaggregating. Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manufacture, and to ensure the particles redisperse into water in a spray tank. They are widely used in wettable powders, suspension concentrates and water-dispersible granules. Surfactants that are used as dispersing agents have the ability to adsorb strongly onto a particle surface and provide a charged or steric barrier to reaggregation of particles. The most commonly used surfactants are anionic, non-ionic, or mixtures of the two types. For wettable powder formulations, the most common dispersing agents are sodium lignosulfonates. For suspension concentrates, very good adsorption and stabilization are obtained using polyelectrolytes, such as sodium naphthalene sulfonate formaldehyde condensates. Tristyrylphenol ethoxylate phosphate esters are also used. Non-ionics such as alkylarylethylene oxide condensates and EO-PO block copolymers are sometimes combined with anionics as dispersing agents for suspension concentrates. In recent years, new types of very high molecular weight polymeric surfactants have been developed as dispersing agents. These have very long hydrophobic 'backbones' and a large number of ethylene oxide chains forming the 'teeth' of a 'comb' surfactant. These high molecular weight polymers can give very good long-term stability to suspension concentrates because the hydrophobic backbones have many anchoring points onto the particle surfaces. Examples of dispersing agents used in agrochemical formulations are: sodium lignosulfonates; sodium naphthalene sulfonate formaldehyde condensates; tristyrylphenol ethoxylate phosphate esters; aliphatic alcohol ethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graft copolymers.

An emulsifying agent is a substance which stabilizes a suspension of droplets of one liquid phase in another liquid phase. Without the emulsifying agent the two liquids would separate into two immiscible liquid phases. The most commonly used emulsifier blends contain alkylphenol or aliphatic alcohol with twelve or more ethylene oxide units and the oil- soluble calcium salt of dodecylbenzenesulfonic acid. A range of hydrophile-lipophile balance ("HLB") values from 8 to 18 will normally provide good stable emulsions. Emulsion stability can sometimes be improved by the addition of a small amount of an EO-PO block copolymer surfactant.

A solubilizing agent is a surfactant which will form micelles in water at

concentrations above the critical micelle concentration. The micelles are then able to dissolve or solubilize water-insoluble materials inside the hydrophobic part of the micelle. The types of surfactants usually used for solubilization are non- ionics, sorbitan monooleates, sorbitan monooleate ethoxylates, and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additives such as mineral or vegetable oils as adjuvants to spray-tank mixes to improve the biological performance of the pesticide on the target. The types of surfactants used for bioenhancement depend generally on the nature and mode of action of the pesticide. However, they are often non-ionics such as: alkyl ethoxylates; linear aliphatic alcohol ethoxylates; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation is a material added to the pesticide to give a product of the required strength. Carriers are usually materials with high absorptive capacities, while diluents are usually materials with low absorptive capacities. Carriers and diluents are used in the formulation of dusts, wettable powders, granules and water- dispersible granules. Organic solvents are used mainly in the formulation of emulsifiable concentrates, oil- in-water emulsions, suspoemulsions, and ultra low volume formulations, and to a lesser extent, granular formulations. Sometimes mixtures of solvents are used. The first main groups of solvents are aliphatic paraffinic oils such as kerosene or refined paraffins. The second main group (and the most common) comprises the aromatic solvents such as xylene and higher molecular weight fractions of C9 and CIO aromatic solvents. Chlorinated hydrocarbons are useful as cosolvents to prevent crystallization of pesticides when the formulation is emulsified into water. Alcohols are sometimes used as cosolvents to increase solvent power. Other solvents may include vegetable oils, seed oils, and esters of vegetable and seed oils.

Thickeners or gelling agents are used mainly in the formulation of suspension concentrates, emulsions and suspoemulsions to modify the rheology or flow properties of the liquid and to prevent separation and settling of the dispersed particles or droplets.

Thickening, gelling, and anti-settling agents generally fall into two categories, namely water- insoluble particulates and water-soluble polymers. It is possible to produce suspension concentrate formulations using clays and silicas. Examples of these types of materials, include, but are not limited to, montmorillonite, bentonite, magnesium aluminum silicate, and attapulgite. Water-soluble polysaccharides have been used as thickening-gelling agents for many years. The types of polysaccharides most commonly used are natural extracts of seeds and seaweeds or are synthetic derivatives of cellulose. Examples of these types of materials include, but are not limited to, guar gum; locust bean gum; carrageenam; alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC); hydroxyethyl cellulose (HEC). Other types of anti-settling agents are based on modified starches, polyacrylates, polyvinyl alcohol and polyethylene oxide. Another good anti-settling agent is xanthan gum.

Microorganisms can cause spoilage of formulated products. Therefore preservation agents are used to eliminate or reduce their effect. Examples of such agents include, but are not limited to: propionic acid and its sodium salt; sorbic acid and its sodium or potassium salts; benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt; methyl p- hydroxybenzoate; and l,2-benzisothiazolin-3-one (BIT).

The presence of surfactants often causes water-based formulations to foam during mixing operations in production and in application through a spray tank. In order to reduce the tendency to foam, anti-foam agents are often added either during the production stage or before filling into bottles. Generally, there are two types of anti-foam agents, namely silicones and non- silicones. Silicones are usually aqueous emulsions of dimethyl polysiloxane, while the non-silicone anti-foam agents are water-insoluble oils, such as octanol and nonanol, or silica. In both cases, the function of the anti-foam agent is to displace the surfactant from the air-water interface.

"Green" agents (e.g., adjuvants, surfactants, solvents) can reduce the overall environmental footprint of crop protection formulations. Green agents are biodegradable and generally derived from natural and/or sustainable sources, e.g. plant and animal sources. Specific examples are: vegetable oils, seed oils, and esters thereof, also alkoxylated alkyl polyglucosides.

For further information, see "Chemistry and Technology of Agrochemical

Formulations" edited by D.A. Knowles, copyright 1998 by Kluwer Academic Publishers. Also see "Insecticides in Agriculture and Environment - Retrospects and Prospects" by A.S. Perry, I. Yamamoto, I. Ishaaya, and R. Perry, copyright 1998 by Springer- Verlag.

PESTS

In general, the molecules of Formula One may be used to control pests e.g. beetles, earwigs, cockroaches, flies, aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.

In another embodiment, the molecules of Formula One may be used to control pests in the Phyla Nematoda and/or Arthropoda.

In another embodiment, the molecules of Formula One may be used to control pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.

In another embodiment, the molecules of Formula One may be used to control pests in the Classes of Arachnida, Symphyla, and/or Insecta.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Anoplura. A non-exhaustive list of particular genera includes, but is not limited to, Haematopinus spp., Hoplopleura spp., Linognathus spp., Pediculus spp., and Polyplax spp. A non-exhaustive list of particular species includes, but is not limited to, Haematopinus asini, Haematopinus suis, Linognathus setosus, Linognathus ovillus, Pediculus humanus capitis, Pediculus humanus humanus, and Pthirus pubis.

In another embodiment, the molecules of Formula One may be used to control pests in the Order Coleoptera. A non-exhaustive list of particular genera includes, but is not limited to, Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp., Bruchus spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrotica spp., Hypera spp., Ips spp., Lyctus spp., Megascelis spp., Meligethes spp., Otiorhynchus spp., Pantomorus spp., Phyllophaga spp., Phyllotreta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp., Scolytus spp., Sphenophorus spp., Sitophilus spp., and Tribolium spp. A non-exhaustive list of particular species includes, but is not limited to, Ac anthosc elides obtectus, Agrilus planipennis, Anoplophora glabripennis, Anthonomus grandis, Ataenius spretulus, Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata, Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi, Conoderus scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Crioceris asparagi, Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptolestes turcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermestes lardarius, Dermestes maculatus, Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera postica, Hypothenemus hampei, Lasioderma serricorne, Leptinotarsa decemlineata, Liogenys fuscus, Liogenys suturalis, Lissorhoptrus oryzophilus, Maecolaspis joliveti, Melanotus communis, Meligethes aeneus, Melolontha melolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros, Oryzaephilus mercator, Oryzaephilus surinamensis, Oulema melanopus, Oulema oryzae, Phyllophaga cuyabana, Popillia japonica, Prostephanus truncatus, Rhyzopertha dominica,, Sitona lineatus,

Sitophilus granarius, Sitophilus oryzae, Sitophilus zeamais, Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogoderma variabile, and Zabrus tenebrioides.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Dermaptera.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Blattaria. A non-exhaustive list of particular species includes, but is not limited to, Blattella germanica, Blatta orientalis, Parcoblatta pennsylvanica, Periplaneta americana, Periplaneta australasiae, Periplaneta brunnea, Periplaneta fuliginosa, Pycnoscelus surinamensis, and Supella longipalpa.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Diptera. A non-exhaustive list of particular genera includes, but is not limited to, Aedes spp., Agromyza spp., Anastrepha spp., Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp., Cochliomyia spp., Contarinia spp., Culex spp., Dasineura spp., Delia spp., Drosophila spp., Fannia spp., Hylemyia spp., Liriomyza spp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp. A non-exhaustive list of particular species includes, but is not limited to, Agromyza frontella, Anastrepha suspensa, Anastrepha ludens, Anastrepha obliqa, Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera invadens, Bactrocera zonata, Ceratitis capitata, Dasineura brassicae, Delia platura, Fannia canicularis, Fannia scalaris, Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma lineatum, Liriomyza brassicae, Melophagus ovinus, Musca autumnalis, Musca domestica, Oestrus ovis, Oscinellafrit, Pegomya betae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax, Sitodiplosis mosellana, and Stomoxys calcitrans.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Hemiptera. A non-exhaustive list of particular genera includes, but is not limited to, Adelges spp., Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp., Lagynotomus spp., Lygus spp., Macrosiphum spp., Nephotettix spp., Nezara spp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcus spp.,

Pseudococcus spp., Rhopalosiphum spp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive list of particular species includes, but is not limited to, Acrosternum hilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixus floccosus, Amrasca biguttula biguttula, Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi, Aulacorthum solani, Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella asparagi, Brevennia rehi, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex hemipterus, Cimex lectularius, Dagbertus fasciatus, Dichelops furcatus, Diuraphis noxia, Diaphorina citri, Dysaphis plantaginea, Dysdercus suturellus, Edessa meditabunda,

Eriosoma lanigerum, Eurygaster maura, Euschistus heros, Euschistus servus, Helopeltis antonii, Helopeltis theivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus, Leptocorisa oratorius, Leptocorisa varicornis, Lygus hesperus, Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium, Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarva jrimbiolata, Metopolophium dirhodum, Mictis longicornis, Myzus persicae, Nephotettix cinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvata lugens, Parlatoria pergandii, Parlatoria ziziphi, Peregrinus maidis, Phylloxera vitifoliae, Physokermes piceae,, Phytocoris californicus, Phytocoris relativus, Piezodorus guildinii, Poecilocapsus lineatus, Psallus vaccinicola, Pseudacysta perseae, Pseudococcus brevipes, Quadraspidiotus perniciosus, Rhopalosiphum maidis, Rhopalosiphum padi, Saissetia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobion avenae, Sogatella furcifera,

Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia entrerriana. In another embodiment, the molecules of Formula One may be used to control pests of the Order Hymenoptera. A non-exhaustive list of particular genera includes, but is not limited to, Acromyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp., Neodiprion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp., Vespula spp., and Xylocopa spp. A non-exhaustive list of particular species includes, but is not limited to, Athalia rosae, Atta texana, Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsis geminata, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, and Tapinoma sessile.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Isoptera. A non-exhaustive list of particular genera includes, but is not limited to, Coptotermes spp., Cornitermes spp., Cryptotermes spp., Heterotermes spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes spp., Microcerotermes spp., Procornitermes spp., Reticulitermes spp., Schedorhinotermes spp., and Zootermopsis spp. A non-exhaustive list of particular species includes, but is not limited to, Coptotermes curvignathus, Coptotermes frenchi, Coptotermes formosanus, Heterotermes aureus,

Microtermes obesi, Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermes flavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, and Reticulitermes virginicus.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Lepidoptera. A non-exhaustive list of particular genera includes, but is not limited to, Adoxophyes spp., Agrotis spp., Argyrotaenia spp., Cacoecia spp., Caloptilia spp., Chilo spp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp., Diatraea spp., Earias spp., Ephestia spp., Epimecis spp., Feltia spp., Gortyna spp., Helicoverpa spp., Heliothis spp., Indarbela spp., Lithocolletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp., Phyllonorycter spp., Pseudaletia spp., Sesamia spp., Spodoptera spp.,

Synanthedon spp., and Yponomeuta spp. A non-exhaustive list of particular species includes, but is not limited to, Achaeajanata, Adoxophyes orana, Agrotis ipsilon, Alabama argillacea, Amorbia cuneana, Amyelois transitella, Anacamptodes defectaria, Anarsia lineatella, Anomis sabulifera, Anticarsia gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbo cinnara, Bucculatrix thurberiella, Capua reticulana, Carposina niponensis, Chlumetia transversa, Choristoneura rosaceana, Cnaphalocrocis medinalis, Conopomorpha cramerella, Cossus cossus, Cydia caryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydia pomonella, Darna diducta, Diatraea saccharalis, Diatraea grandiosella, Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpus lignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella, Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoecilia ambiguella, Euxoa auxiliaris, Grapholita molesta, Hedylepta indicata, Helicoverpa armigera,

Helicoverpa zea, Heliothis virescens, Hellula undalis, Keiferia lycopersicella, Leucinodes orbonalis, Leucoptera coffeella, Leucoptera malifoliella, Lobesia botrana, Loxagrotis albicosta, Lymantria dispar, Lyonetia clerkella, Mahasena corbetti, Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta, Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus, Pectinophora gossypiella, Peridroma saucia, Perileucoptera coffeella, Phthorimaea operculella, Phyllocnistis citrella, Pieris rapae, Plathypena scabra, Plodia interpunctella, Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu, Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens, Sitotroga cerealella, Sparganothis pilleriana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera eridania, Thecla basilides, Tineola bisselliella, Trichoplusia ni, Tuta absoluta, Zeuzera coffeae, and Zeuzera pyrina.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Mallophaga. A non-exhaustive list of particular genera includes, but is not limited to, Anaticola spp., Bovicola spp., Chelopistes spp., Goniodes spp., Menacanthus spp., and Trichodectes spp. A non-exhaustive list of particular species includes, but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthus stramineus, Menopon gallinae, and Trichodectes canis.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Orthoptera. A non-exhaustive list of particular genera includes, but is not limited to, Melanoplus spp., and Pterophylla spp. A non-exhaustive list of particular species includes, but is not limited to, Anabrus simplex, Gryllotalpa africana, Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta migratoria, Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Siphonaptera. A non-exhaustive list of particular species includes, but is not limited to, Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canis,

Ctenocephalides felis, and Pulex irritans. In another embodiment, the molecules of Formula One may be used to control pests of the Order Thysanoptera. A non-exhaustive list of particular genera includes, but is not limited to, Caliothrips spp., Frankliniella spp., Scirtothrips spp., and Thrips spp. A non- exhaustive list of particular sp. includes, but is not limited to, Frankliniella fusca,

Frankliniella occidentalis, Frankliniella schultzei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips dorsalis, and Taeniothrips rhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thrips orientalis, Thrips t abaci.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Thysanura. A non-exhaustive list of particular genera includes, but is not limited to, Lepisma spp. and Thermobia spp.

In another embodiment, the molecules of Formula One may be used to control pests of the Order Acarina. A non-exhaustive list of particular genera includes, but is not limited to, Acarus spp., Aculops spp., Boophilus spp., Demodex spp., Dermacentor spp., Epitrimerus spp., Eriophyes spp., Ixodes spp., Oligonychus spp., Panonychus spp., Rhizoglyphus spp., and Tetranychus spp. A non-exhaustive list of particular species includes, but is not limited to, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyomma americanum, Brevipalpus obovatus, Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoides pteronyssinus, Eotetranychus carpini, Notoedres cati, Oligonychus coffeae, Oligonychus ilicis, Panonychus citri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemus lotus, Rhipicephalus sanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychus urticae, and Varroa destructor.

In another embodiment, the molecules of Formula One may be used to control pest of the Order Symphyla. A non-exhaustive list of particular sp. includes, but is not limited to, Scutigerella immaculata.

In another embodiment, the molecules of Formula One may be used to control pests of the Phylum Nematoda. A non-exhaustive list of particular genera includes, but is not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp., Hirschmanniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus spp. A non-exhaustive list of particular sp. includes, but is not limited to, Dirofilaria immitis, Heterodera zeae, Meloidogyne incognita, Meloidogyne javanica, Onchocerca volvulus, Radopholus similis, and Rotylenchulus reniformis. For additional information consult "HANDBOOK OF PEST CONTROL - THE

APPLICATIONS

Molecules of Formula One are generally used in amounts from about 0.01 grams per hectare to about 5000 grams per hectare to provide control. Amounts from about 0.1 grams per hectare to about 500 grams per hectare are generally preferred, and amounts from about 1 gram per hectare to about 50 grams per hectare are generally more preferred.

The area to which a molecule of Formula One is applied can be any area inhabited (or maybe inhabited, or traversed by) a pest, for example: where crops, trees, fruits, cereals, fodder species, vines, turf and ornamental plants, are growing; where domesticated animals are residing; the interior or exterior surfaces of buildings (such as places where grains are stored), the materials of construction used in building (such as impregnated wood), and the soil around buildings. Particular crop areas to use a molecule of Formula One include areas where apples, corn, sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, beans and other valuable crops are growing or the seeds thereof are going to be planted. It is also advantageous to use ammonium sulfate with a molecule of Formula One when growing various plants.

Controlling pests generally means that pest populations, pest activity, or both, are reduced in an area. This can come about when: pest populations are repulsed from an area; when pests are incapacitated in or around an area; or pests are exterminated, in whole, or in part, in or around an area. Of course, a combination of these results can occur. Generally, pest populations, activity, or both are desirably reduced more than fifty percent, preferably more than 90 percent. Generally, the area is not in or on a human; consequently, the locus is generally a non-human area.

The molecules of Formula One may be used in mixtures, applied simultaneously or sequentially, alone or with other compounds to enhance plant vigor (e.g. to grow a better root system, to better withstand stressful growing conditions). Such other compounds are, for example, compounds that modulate plant ethylene receptors, most notably 1- methylcyclopropene (also known as 1-MCP). Furthermore, such molecules may be used during times when pest activity is low, such as before the plants that are growing begin to produce valuable agricultural commodities. Such times include the early planting season when pest pressure is usually low. The molecules of Formula One can be applied to the foliar and fruiting portions of plants to control pests. The molecules will either come in direct contact with the pest, or the pest will consume the pesticide when eating leaf, fruit mass, or extracting sap, that contains the pesticide. The molecules of Formula One can also be applied to the soil, and when applied in this manner, root and stem feeding pests can be controlled. The roots can absorb a molecule taking it up into the foliar portions of the plant to control above ground chewing and sap feeding pests.

Generally, with baits, the baits are placed in the ground where, for example, termites can come into contact with, and/or be attracted to, the bait. Baits can also be applied to a surface of a building, (horizontal, vertical, or slant surface) where, for example, ants, termites, cockroaches, and flies, can come into contact with, and/or be attracted to, the bait. Baits can comprise a molecule of Formula One.

The molecules of Formula One can be encapsulated inside, or placed on the surface of a capsule. The size of the capsules can range from nanometer size (about 100-900 nanometers in diameter) to micrometer size (about 10-900 microns in diameter).

Because of the unique ability of the eggs of some pests to resist certain pesticides, repeated applications of the molecules of Formula One may be desirable to control newly emerged larvae.

Systemic movement of pesticides in plants may be utilized to control pests on one portion of the plant by applying (for example by spraying an area) the molecules of Formula One to a different portion of the plant. For example, control of foliar- feeding insects can be achieved by drip irrigation or furrow application, by treating the soil with for example pre- or post-planting soil drench, or by treating the seeds of a plant before planting.

Seed treatment can be applied to all types of seeds, including those from which plants genetically modified to express specialized traits will germinate. Representative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicide resistance, such as "Roundup Ready" seed, or those with "stacked" foreign genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, drought resistance, or any other beneficial traits.

Furthermore, such seed treatments with the molecules of Formula One may further enhance the ability of a plant to better withstand stressful growing conditions. This results in a healthier, more vigorous plant, which can lead to higher yields at harvest time. Generally, about 1 gram of the molecules of Formula One to about 500 grams per 100,000 seeds is expected to provide good benefits, amounts from about 10 grams to about 100 grams per 100,000 seeds is expected to provide better benefits, and amounts from about 25 grams to about 75 grams per 100,000 seeds is expected to provide even better benefits.

It should be readily apparent that the molecules of Formula One may be used on, in, or around plants genetically modified to express specialized traits, such as Bacillus thuringiensis or other insecticidal toxins, or those expressing herbicide resistance, or those with "stacked" foreign genes expressing insecticidal toxins, herbicide resistance, nutrition- enhancement, or any other beneficial traits.

The molecules of Formula One may be used for controlling endoparasites and ectoparasites in the veterinary medicine sector or in the field of non-human animal keeping. The molecules of Formula One are applied, such as by oral administration in the form of, for example, tablets, capsules, drinks, granules, by dermal application in the form of, for example, dipping, spraying, pouring on, spotting on, and dusting, and by parenteral administration in the form of, for example, an injection.

The molecules of Formula One may also be employed advantageously in livestock keeping, for example, cattle, sheep, pigs, chickens, and geese. They may also be employed advantageously in pets such as, horses, dogs, and cats. Particular pests to control would be fleas and ticks that are bothersome to such animals. Suitable formulations are administered orally to the animals with the drinking water or feed. The dosages and formulations that are suitable depend on the species.

The molecules of Formula One may also be used for controlling parasitic worms, especially of the intestine, in the animals listed above.

The molecules of Formula One may also be employed in therapeutic methods for human health care. Such methods include, but are limited to, oral administration in the form of, for example, tablets, capsules, drinks, granules, and by dermal application.

Pests around the world have been migrating to new environments (for such pest) and thereafter becoming a new invasive species in such new environment. The molecules of Formula One may also be used on such new invasive species to control them in such new environment.

The molecules of Formula One may also be used in an area where plants, such as crops, are growing (e.g. pre-planting, planting, pre-harvesting) and where there are low levels (even no actual presence) of pests that can commercially damage such plants. The use of such molecules in such area is to benefit the plants being grown in the area. Such benefits, may include, but are not limited to, improving the health of a plant, improving the yield of a plant (e.g. increased biomass and/or increased content of valuable ingredients), improving the vigor of a plant (e.g. improved plant growth and/or greener leaves), improving the quality of a plant (e.g. improved content or composition of certain ingredients), and improving the tolerance to abiotic and/or biotic stress of the plant.

Before a pesticide can be used or sold commercially, such pesticide undergoes lengthy evaluation processes by various governmental authorities (local, regional, state, national, and international). Voluminous data requirements are specified by regulatory authorities and must be addressed through data generation and submission by the product registrant or by a third party on the product registrant's behalf, often using a computer with a connection to the World Wide Web. These governmental authorities then review such data and if a determination of safety is concluded, provide the potential user or seller with product registration approval. Thereafter, in that locality where the product registration is granted and supported, such user or seller may use or sell such pesticide.

A molecule according to Formula One can be tested to determine its efficacy against pests. Furthermore, mode of action studies can be conducted to determine if said molecule has a different mode of action than other pesticides. Thereafter, such acquired data can be disseminated, such as by the internet, to third parties.

The headings in this document are for convenience only and must not be used to interpret any portion hereof.

TABLE SECTION

GPA Rating Table

% Control (or Mortality) Rating

80-100 A

More than 0 - Less than 80 B

Not Tested C

No activity noticed in this bioassay D

Table 1: Structures for Compounds

AC72

AC75

AC76

AC77

AC78

AC79

BC8

BC9

BCIO

BC11

BC12

BC13

Table 1A: Structures of Prophetic F Compounds Subsequently Exemplified Table IB: Structures of FA Compounds Subsequently Exemplified

Table 2: Analytical Data for Compounds in Table 1. 7.67 (s, 3H), 7.64 (d,7 =

8.0 Hz, 2H), 7.42 (d, 7 =

8.0 Hz, 2H), 6.91 (dd, 7

444.12

AC5 = 15.6, 8.0 Hz, IH),

«M+H]⁺)

6.80 (d,7 = 15.6 Hz,

IH), 4.80 (m, IH), 3.60

(br s, 8H)

7.40 (m, 2H), 7.26 (m,

3H), 6.56 (d,7 = 16.0

468.40 Hz, IH), 6.48 (dd, 7 = 1657, 1113,

AC6

([M-H]-) 16.0, 8.0 Hz, IH), 5.82 804

(br s, IH), 4.08 (m, 3H),

2.52 (s, 3H)

8.39 (s, IH), 7.74 (m,

IH), 7.39 (m, 3H), 7.24

(m, 4H), 6.58 (d, 7 =

511.02 16.0 Hz, IH), 6.38 (dd, 3276, 1645,

AC7

([M-H]) 7 = 16.0, 8.0 Hz, IH), 1111,801

6.16 (brs, IH), 4.63 (m,

2H),4.12 (m, IH), 2.41

(s, 3H)

7.39 (s, IH), 7.22 (m,

2H),7.19(m, 3H), 6.53

(d,7 = 16.0 Hz, IH),

6.39-6.34 (dd,7 = 16.0,

454.11 1748, 1112,

AC8 8.0 Hz, IH), 4.22 (m,

([M-H]^") 801

IH), 3.95 (t, 7 = 7.0 Hz,

2H),2.62 (t, 7=8.0 Hz,

2H),2.30 (s, 3H),2.18

(m, 2H)

7.45 (t, 7 = 7.6 Hz, IH),

7.36 (m, 2H), 7.21 (m,

3H),7.15 (m, 4H), 6.56

(d,7= 16.0 Hz, IH),

494.02 3276, 1645,

AC9 6.38 (dd, 7= 16.0, 8.4

([M-H]^") 1112, 801

Hz, IH), 6.08 (br s, IH),

4.68 (d, 7 =5.6 Hz, 2H),

4.11 (m, 1H),2.44 (s,

3H) 7.38 (t,/ = 1.6 Hz, 1H),

7.34 (d, 7=7.6 Hz, 1H),

7.27 (m, 2H), 7.24 (m,

2H), 6.57 (d,/ = 16.0

140- 458.00 Hz, 1H), 6.40 (dd, / =

A10

143 ([M-H]-) 16.0, 8.0 Hz, 1H), 6.16

(m 1H), 5.44 (m, 1H),

4.12 (m, 1H), 3.51 (m,

2H), 3.40 (m, 2H), 2.44

(s, 3H)

7.39-7.29 (m, 9H), 7.24

(m, 2H), 6.56 (d,/ =

16.0 Hz, 1H), 6.38 (dd,

476.17 3287, 1644,

AC11 / = 16.0, 8.0 Hz, 1H),

([M-H]^") 1112, 801

5.99 (br s, 1H), 4.63 (d,

7=6.0 Hz, 1H), 4.11

(m, 1H), 2.47 (s, 3H)

8.63 (d, J = 4.4 Hz, 1H),

7.71 (m, 1H), 7.47 (d, J

= 8.4 Hz, 1H), 7.37 (m,

2H), 7.32 (m, 2H), 7.23

479.30 (m, 2H), 7.13 (m, 1H), 3293, 1653,

AC12

«M+H]⁺) 6.58 (d,/= 16.0 Hz, 1112, 800

1H), 6.40 (dd,/= 16.0,

8.0 Hz, 1H), 4.75 (d,/ =

4.8 Hz, 2H), 4.12 (m,

1H), 2.49 (s, 3H)

7.38 (m, 2H), 7.27 (m,

3H), 7.23 (br s, 1H),

6.58 (d,/= 16.0 Hz,

1H), 6.45 (m 1H), 6.42

490.04

AC13 75-78 (dd,/= 16.0, 8.4 Hz,

([M-H]^")

1H), 4.91 (m 1H), 4.64

(m, 2H), 4.14 (m, 1H),

4.04 (m, 2H), 2.46 (s,

3H)

8.63 (s,2H), 7.76 (d,/ =

8.0 Hz, 1H), 7.36 (m,

3H), 7.22 (m, 1H), 7.13

480.99 (m, 2H), 6.57 (d,/ =

3293, 1645,

AC14 ([M+2H]⁺ 16.0 Hz, 1H), 6.39 (dd,

1113,800

) /= 16.0, 8.0 Hz, 1H),

6.13 (brs, 1H), 4.66 (d,

7=5.6 Hz, 2H), 4.11

(m, 1H), 2.46 (s, 3H) 7.45 (s, IH), 7.37 (m,

IH), 7.34 (m, IH), 7.26

(m, 3H), 7.22 (m, IH),

6.57 (d, 7 = 16.0 Hz,

516.86 3246, 1635,

AC15 59-61 IH), 6.40 (dd, 7 = 16.0,

([M-H]-) 1112, 801

8.0 Hz, IH), 6.18 (m,

IH), 4.71 (d, 7 = 6.4 Hz,

2H), 4.11 (m, IH), 2.46

(s, 3H)

8.47 (m, IH), 8.19 (s,

IH), 7.76 (m, IH), 7.47

(m, 2H), 7.37 (m, IH),

7.28 (m, 2H), 7.24 (m,

506.93 IH), 7.21 (m, IH), 6.59 1657, 1113,

AC16

([M+H]⁺) (d, 7 = 16.0 Hz, IH), 801

6.39 (dd, 7 = 16.0, 8.4

Hz, IH), 4.12 (m, IH),

2.48 (s, 3H), 1.88 (s,

6H)

7.49 (m, 2H), 7.38 (m,

IH), 7.29 (m, 4H), 7.08

(m, 3H), 6.91 (m, IH),

494.98 6.61 (d, 7 = 16.0 Hz,

AC17 70-73

([M-H]^") IH), 6.48 (m, IH), 6.43

(dd, 7 = 16.0, 8.0 Hz,

lH), 4.13 (m, IH), 2.49

(s, 3H)

8.73 (d, 7 = 4.8 Hz, 2H),

7.53 (d, 7 = 8.4 Hz, IH),

7.37 (m, IH), 7.27 (m,

4H), 7.23 (m, IH), 7.11

155- 480.44 (m, IH), 6.60 (d, 7 =

AC18

158 «M+H]⁺) 16.0 Hz, IH), 6.41 (dd,

7 = 16.0, 8.0 Hz, IH),

4.90 (d, 7 = 4.8 Hz, 2H),

4.13 (m, 1H), 2.52 (s,

3H) 7.37 (m, IH), 7.33 (d, J

= 7.6 Hz, IH), 7.27 (m,

2H), 7.22 (m, 2H), 6.57

(d,/ = 16.0 Hz, IH),

6.39 (dd, 7=16.0, 8.0

471.66

AC19 55-57 Hz, IH), 6.10 (brs, IH),

([Μ+ΗΓ)

4.13 (m, 2H), 3.94 (m,

IH), 3.79 (m, 2H), 3.35

(m, IH), 2.45 (s, 3H),

2.14 (m, IH), 1.71 (m,

2H), 1.65 (m, IH).

7.37 (m, 2H), 7.27 (m,

2H), 7.23 (m, 2H), 6.57

(d,/ = 16.0 Hz, IH), 3437, 1664,

467.68

AC20 6.38 (m, 3H), 6.01 (m, 1265, 1114,

«M+H]⁺)

1H),4.63 (d, 7=5.6 Hz, 746 2H),4.13(m, IH), 2.45

(s, 3H)

8.44 (s, IH), 8.18 (s,

IH), 7.83 (br s, IH),

7.38 (m, 2H), 7.27 (m,

2H), 7.25 (m, 2H), 7.21

528.78

AC21 61-64 (m, IH), 6.57 (d,/ =

«M+H]⁺)

16.0 Hz, IH), 6.40 (dd,

/= 16.0, 8.0 Hz, IH),

5.01 (s,2H), 4.11 (m,

IH), 2.43 (s, 3H)

8.39 (s, IH), 7.73 (m,

IH), 7.40 (s, IH), 7.35

(m, 2H), 7.22 (m, 3H),

6.57 (d,/ = 16.0 Hz,

545.08 3270, 1642,

AC22 IH), 6.38 (dd,/= 16.0,

([M-H]-) 1111,809

7.6 Hz, IH), 6.14 (brs,

1H),4.62 (d, 7=6.0 Hz,

2H),4.13(m, IH), 2.45

(s, 3H)

7.42 (s, 2H), 7.36 (m,

IH), 7.24 (m, 2H), 6.59

(d,/= 16.0 Hz, IH),

3273, 1641,

492.35 6.40 (dd,/= 16.0, 8.0

AC23 1250, 1113,

([M-H]) Hz, IH), 6.20 (br s, IH),

807 5.46 (m, 1H),4.15 (m,

IH), 3.52 (m, 2H), 3.41

(m, 2H), 2.45 (s, 3H) 7.40 (m, 2H), 7.27 (m,

2H), 7.25 (m, 2H), 6.92

(br s, 2H), 6.60 (m, IH),

129- 526.98 6.48(dd,7 = 16.0,8.0 3298, 1664,

AC24

132 ([Μ+ΗΓ) Hz, 1H),4.19 (d,7 = 1113,803

5.2, 2H), 4.08 (m, IH),

3.99 (m, 2H), 2.46 (s,

3H)

7.41 (m, 3H), 7.27 (m,

2H), 6.58 (d,7 = 15.6

3257, 1652,

542.24 Hz, IH), 6.42 (m, 2H),

AC25 1316, 1109,

([M-H]) 4.92 (m, IH), 4.65 (m,

807 2H),4.14 (m, IH), 4.09

(m, 2H), 2.46 (s, 3H)

7.45 (s, IH), 7.40 (s,

2H),7.34 (d, 7=8.0 Hz,

IH), 7.22 (m, 2H), 6.54

550.69 (d,7 = 16.0 Hz, IH), 3255, 1638,

AC26

([M-H]^") 6.38 (dd, 7=16.0, 8.0 1113,809

Hz, IH), 4.71 (d, 7 = 6.0

Hz, 2H), 4.11 (m, IH),

2.46 (s, 3H)

8.46 (d, 7 = 4.0 Hz, IH),

8.20 (s, IH), 7.76 (m,

IH), 7.47 (m, 2H), 7.41

(s, 2H), 7.23 (m, 2H),

541.00 1653, 1113,

AC27 7.21 (m, IH), 6.59 (d, 7

([M-H]^") 809

= 16.0 Hz, IH), 6.37

(dd,7= 16.0, 8.4 Hz,

1H),4.11 (m, IH), 2.48

(s, 3H), 1.88 (s, 6H)

8.40 (s, IH), 7.74 (m,

2H), 7.42 (m, 3H), 7.36

(m, 2H), 6.72 (br s, IH),

564.84 6.52 (d,7= 16.0 Hz, 3267,1650,

AC28 65-67

([M-H]) IH), 6.43 (dd,7=16.0, 1112, 809

8.0 Hz, IH), 4.66 (d,7 =

6.4 Hz, 2H), 4.12 (m,

IH) 7.71 (d,/ = 8.4 Hz, IH),

7.42 (m, 3H), 7.35 (m, IH), 6.75 (br s, IH),

511.78 6.56 (d,/ = 16.0 Hz,

AC29 75-78

([M-H]-) IH), 6.43 (dd,/ = 16.0,

8.0 Hz, IH), 5.49 (m, 1H),4.14 (m, IH), 3.50 (m, 4H)

7.42 (d, 7=8.4 Hz, IH), 7.44 (s, IH), 7.40 (s, IH), 7.38 (m, IH), 7.06

110- 543.72 (brs, IH), 6.58 (d,/ =

AC30

113 ([M-H]) 15.6 Hz, IH), 6.45 (dd,

/ = 15.6, 8.0 Hz, IH), 4.93 (m, IH), 4.65 (m, 2H),4.13(m, 3H)

8.42 (s, IH), 7.76 (m, IH), 7.61 (m, 2H), 7.39

610.73

AC31 68-70 (m, 4H), 6.54 -6.39 (m,

([M+H]⁺)

3H),4.66 (d, 7=6.0 Hz, 2H),4.12 (m, IH)

7.61 (m, 2H), 7.40 (m, 3H), 6.54 (m, 2H), 6.40

555.89

AC32 78-80 (dd,/= 16.0, 8.0 Hz,

([M-H]^")

IH), 5.46 (m, IH), 4.14 (m, IH), 3.50 (m, 4H)

7.62 (s, IH), 7.58 (d,/ = 8.0 Hz, IH), 7.40 (m, 3H), 6.84 (br s, IH),

182- 587.68 6.55 (d,/= 15.6 Hz,

AC33

184 ([M-H]^") IH), 6.45 (dd, 7=15.6,

7.6 Hz, IH), 4.93 (m 1H),4.65 (m, 2H), 4.13 (m, 4H)

7.67 (s, IH), 7.61 (d,/ = 6.0 Hz, IH), 7.53 (m, IH), 7.41 (s, 2H), 6.64 (d,/= 16.0 Hz, IH),

151- 545.83

AC34 6.40 (dd,/= 16.0, 8.0

153 ([M-H])

Hz, IH), 6.18 (brs, IH), 5.44 (m, lH),4.14(m, IH), 3.50 (m, 2H), 3.40 (m, 2H) 7.70 (s, IH), 7.63 (m,

1H),7.53 (d, 7 = 7.6 Hz,

IH), 7.41 (s, 2H), 6.53

100- 577.71 3257, 1655,

AC35 (d,7 = 16.0 Hz, IH),

102 ([M-H]) 1113,808

6.49 (m, 2H), 4.93 (m,

1H),4.64 (m, 2H), 4.13

(m, IH), 4.03 (m, 2H)

8.40 (s, IH), 7.73 (m,

2H), 7.61 (d, 7=8.4 Hz,

1H),7.52 (d, 7=8.0 Hz,

IH), 7.40 (s, 2H), 7.35

600.83 (d, 7 = 8.0 Hz, IH), 6.63

AC36 81-83

([M+H]⁺) (d,7= 16.0 Hz, IH),

6.46 (dd,7= 16.0,7.6

Hz, IH), 6.14 (m, IH),

4.63 (d, 7 =6.0 Hz, 2H),

4.14 (m, IH)

8.39 (s, IH), 7.73 (m,

IH), 7.48 (m, 2H), 7.34

(d, 7 = 7.6 Hz, IH), 7.24

(m, 3H), 6.55 (d, 7 =

512.68 3268, 1644,

AC37 16.0 Hz, IH), 6.41 (dd,

([M+H]⁺) 1109,820

7= 16.0, 7.6 Hz, IH),

6.12 (m, 1H),4.62 (d, 7

= 6.0 Hz, 2H), 4.13 (m,

IH), 2.45 (s, 3H)

8.46 (m, IH), 7.73 (m,

IH), 7.35 (m, 4H), 7.22

(m, 2H), 6.56 (d, 7 =

528.85 16.0 Hz, IH), 6.38 (dd,

AC38 79-80

([M-H]^") 7= 16.0, 8.0 Hz, IH),

4.62 (d, 7 =6.0 Hz, 2H),

4.10 (m, 1H),2.45 (s,

3H)

9.19 (s, IH), 8.79 (s,

2H), 7.37 (m, 2H), 7.23

(m, 2H), 7.21 (m, IH),

6.57 (d,7= 16.0 Hz,

141- 477.83

AC39 IH), 6.40 (dd, 7=16.0,

144 ([M-H]^") 7.6 Hz IH), 6.21 (m,

1H),4.65 (s, 2H),4.11

(m, IH), 2.46 (s, 3H) 8.33 (t, 7 = 5.6 Hz, IH),

8.61 (m, IH), 7.68 (m,

3H), 7.48 (m, 2H), 6.86

(dd, 7 = 15.6, 8.2 Hz

484.67 IH), 6.74 (d,7 = 15.6

AC40 69-72

«M+H]⁺) Hz, IH), 4.44 (m, IH),

3.76 (d, 7=6.0 Hz, 2H),

2.54 (m, IH), 2.67 (s,

3H), 0.59 (m, 2H), 0.54

(m, 2H)

8.66 (d, 7 = 7.6 Hz,

IH), 8.39 (t, 7 =5.6 Hz,

IH), 7.65 (s, 3H), 7.45

(m, 3H), 6.86 (dd, 7 =

196- 515.00 15.6, 8.8 Hz, IH), 6.74

AC41 (d,7= 15.6 Hz, IH),

199 ([M-H]-) 5.01 (m, IH), 4.99 (m,

IH), 3.78 (d,7=6.0

Hz, 2H), 3.40 (m, 2H),

3.22 (m, 2H), 2.37 (m,

3H)

7.99 (d,7 = 8.0 Hz,

1H),7.89 (d,7=8.0

Hz, IH), 7.51 (m, 2H),

7.44 (m, 2H), 7.27 (m,

534.72 4H), 6.71 (t, 7=5.2 Hz,

AC42 79-82 IH), 6.59 (d,7= 16.0

«M+H]⁺) Hz, IH), 6.41 (dd, 7 =

16.0, 8.0 Hz, IH), 5.05

(d,7=1.6 Hz, 2H),

4.12 (m, 1H),2.52 (m,

3H)

8.69 (s, IH), 8.52 (s,

2H), 7.45 (d, 7 = 7.6 Hz,

IH), 7.37 (d, 7 = 2.0 Hz,

IH), 7.26 (m, 2H), 7.21

481.75 1663,

(m, IH), 6.83 (s, IH),

AC43 1608,1168,

([M+H]⁺) 6.58 (d, 7= 16.0 Hz,

1114, 801 IH), 6.40 (dd,7= 16.0,

8.4 Hz, IH), 4.81 (d, 7 =

5.6 Hz, 2H), 4.12 (t, 7 =

8.4 Hz IH), 2.45 (s, 3H) 8.44 (d, J =2.4 Hz, IH),

7.69 (d, J =2.4 Hz,

IH), 7.37 (m, IH), 7.33

(s, IH), 7.31 (s, IH),

7.26 (m, IH), 7.24 (m,

528.01 3H), 6.57 (d,7 = 16.0

1640, 1166,

AC44 Hz, IH), 6.39 (dd,7 =

([Μ+ΗΓ) 1112, 800

16.0, 8.0 Hz, IH), 5.96

(d, 7 = 7.2 Hz, IH), 5.32

(t, 7 = 7.2 Hz, IH), 4.11

(t, 7=8.4 Hz, IH), 2.41

(s, 3H), 1.61 (d,7=7.2

Hz, 3H)

7.66 (s, IH), 7.37 (d,7 =

6.8 Hz, 2H), 7.26 (m,

3H), 7.18(m, IH), 7.11

512.88 (m, 2H), 6.99 (m, IH),

1657, 1167,

AC45 6.57 (d,7= 15.6 Hz,

«M+H]⁺) 1106, 800

IH), 6.39 (dd,7= 15.6,

8.0 Hz, IH), 4.11 (t, 7 =

8.4 Hz, IH), 3.36 (s,

3H), 2.43 (s, 3H)

8.42 (d, 7 = 2.0 Hz, IH),

7.76 (d, 7 = 2.4 Hz, IH),

7.61 (m, 2H), 7.39 (m,

575.93 3H), 7.26 (s, 2H), 6.54

AC46 61-64

«M+H]⁺) (d,7= 16.0 Hz, IH),

6.42 (dd,7= 16.0,7.6

Hz, 1H),4.65 (d,7 = 6.0

Hz, 2H), 4.14 (m, IH)

10.02 (s, IH), 9.87 (s,

IH), 8.47 (t, 7 =6.0 Hz,

IH), 7.66 (s, 3H), 7.44

(s, IH), 7.40 (d,7=3.6

525.89 Hz, 2H), 6.86 (dd,7 =

AC47 15.6, 9.2 Hz, IH), 6.74 3280, 1640

([M-H]-) (d,7= 15.6 Hz, IH),

4.82 (t,7 = 9.6 Hz, 2H),

3.88 (d, 7 =6.0 Hz, 2H),

2.36 (s, 3H), 1.63 (m,

IH), 0.76 (m, 4H) 7.37 (m, 7H), 7.34 (m,

3H), , 6.57 (d, J = 16.0

509.96 Hz, 1H), 6.39 (dd, / =

AC48 16.0, 8.0 Hz, 1H), 6.01 3275, 1642

([M-H]-) (m, 1H), 4.60 (d, 7 = 6.0

Hz, 2H), 4.13 (m, 1H),

2.46 (s, 3H)

8.39 (d, J = 2.0 Hz, 1H),

8.11 (m, 1H), 7.71 (d, J

= 2.4 Hz, 1H), 7.41 (m,

518.85 3H), 7.17 (m, 3H), 6.59

1658, 1112,

AC49 (d, / = 16.0 Hz, 1H),

«M+H]⁺) 1025, 2219

6.47 (dd, / = 16.0, 8.0

Hz, 1H), 4.66 (d, / =

5.6 Hz, 2H), 4.14 (m,

1H)

8.72 (m, 1H), 7.67 (s,

3H), 7.46 (s, 1H), 7.40

481.88 (m, 2H), 7.08 (s, 1H),

1654, 1112,

AC50 6.82 (m, 2H), 6.55 (d, J

([M+H]⁺) 800, 3069

= 7.6 Hz, 1H), 4.82 (m,

1H), 4.48 (s, 2H), 3.65

(s, 3H), 2.38 (s, 3H)

7.45 (d, 7 = 7.6 Hz, 1H),

7.38 (m, 1H), 7.27 (m,

2H), 7.22 (m, 2H), 6.85

540.83 (m, 1H), 6.58 (d, / = 1652, 1571,

AC51 16.0 Hz, 1H), 6.40 (dd, 802, 1114,

«M+H]⁺) / = 16.0, 8.0 Hz, 1H), 2926

4.33 (m, 2H), 4.14 (m,

3H), 3.18 (s, 3H), 2.48

(s, 3H)

7.33 (m, 2H), 7.25 (m,

3H), 6.56 (d, / = 15.6

Hz, 1H), 6.37 (dd, / =

15.6, 8.0 Hz, 1H), 5.61

488.29 (d, 7 = 8.0 Hz, 1H), 4.21 1635, 11134,

AC52

([M-H] ) (m, 1H), 4.01 (m, 1H), 813, 2927

4.08 (m, 2H), 3.56 (t, J

= 10.0 Hz, 2H), 2.48 (m,

2H), 2.08 (m, 2H), 1.5

(m, 3H) 8.49 (d, J =2.0 Hz, IH),

7.69 (d, J =2.4 Hz, IH),

7.43 (d, 7=8.0 Hz, IH),

7.34 (m, 3H), 7.26 (m,

532.92 2H), 6.95 (m, IH), 6.58 1651, 3027,

AC53

([Μ+ΗΓ) (d,7 = 16.0 Hz, IH), 815, 1113

6.38 (dd, 7=16.0, 8.0

Hz, IH), 4.72 (d, 7=5.2

Hz, 2H), 4.09 (m, IH),

2.47 (s, 3H)

8.37 (d, 7 =5.2 Hz, IH),

7.41 (d, 7 =8.0 Hz, IH),

7.36 (m, 3H),7.31 (m,

IH), 7.26 (m, 2H), 6.58

529.06 (d,7= 16.0 Hz, IH), 1654, 3434,

AC54

([M-H]) 6.40 (dd,7= 16.0,7.6 814, 1112

Hz, IH), 5.20 (t,7=5.6

Hz, 1H),4.63 (d,7 = 6.0

Hz, 2H), 4.13 (m, IH),

2.18 (s,3H)

8.69 (t,7 = 6.0 Hz, IH),

8.58 (t, 7 = 6.0 Hz, IH),

7.92 (s, IH), 7.87 (d,7 =

6.4 Hz, 2H), 7.62 (d, 7 =

8.4 Hz, IH), 7.45 (d, 7 =

464.96 8.4 Hz, IH), 7.0 (m, 3417, 1658,

AC57

([M+H]⁺) IH), 6.76 (d,7= 15.6 1165,817

Hz, IH), 6.76 (dd, 7 =

15.6, 8.0 Hz, IH), 4.01

(m, 7 =8.0 Hz, IH),

3.71 (m, 2H), 3.49 (m,

2H)

7.62 (m, 2H), 7.40 (s,

2H), 7.37 (d, 7= 1.6 Hz,

IH), 6.61 (t, 7 = 4.8 Hz,

124.4- 599.76 IH), 6.55 (d, 7= 16.0

AC58

126.9 «M+H]⁺) Hz, IH), 6.41 (dd, 7 =

16.0, 7.6 Hz, IH), 4.16

(d, 7 = 6.0 Hz, 2H), 4.01

(m, IH), 1.56 (s, 9H) 8.42 (d, 7 = 2.1 Hz, IH),

8.29 (d, 7 = 7.5 Hz, IH),

7.51 (m, 2H), 7.39 (m,

497.40 IH), 7.36 (m, 4H), 7.28

AC59 80-83 (m, IH), 6.61 (d,7 =

([M-H]-) 15.9 Hz, IH), 6.45 (dd,

7= 15.9, 7.8 Hz IH),

4.14 (t, 7 = 8.4 Hz, IH),

2.51 (s, 3H)

8.52 (s, IH), 8.39 (d, 7 =

1.8 Hz, 2H), 7.70 (d, 7 =

2.1Hz, IH), 7.62 (s,

IH), 7.43 (s, IH), 7.35

515.09 1668, 1589,

(m, 3H), 6.62 (d,7 =

AC60 1167, 1113,

([M+H]-) 16.2 Hz, IH), 6.52 (dd,

802

7= 16.2, 7.5 Hz, IH),

4.62 (d, 7 =6.3 Hz,

2H),4.19(m, IH), 2.76

(s, 3H)

8.07 (t, 7 = 8.0 Hz, IH),

7.39 (t, 7 = 2.0 Hz, IH),

7.28 (d, 7= 1.2 Hz, 3H),

7.17 (d, 7= 1.6 Hz, IH),

461.90 7.11 (m, IH), 6.59 (d, 7 1658, 1114,

AC61

([M-H]^") = 15.6 Hz, IH), 6.47 801

(dd,7= 15.6, 7.6 Hz,

IH), 5.49 (m, IH), 4.14

(t,7=8.4 Hz, IH), 3.48

(m, 4H)

8.62 (t,7 = 6.4 Hz, IH),

8.46 (m, IH), 7.73 (m,

5H),7.48 (d,7 = 7.6 Hz,

105- 528.88

AC62 1H),7.03 (dd,7= 15.6,

108 ([M-H]) 9.2 Hz, IH), 6.81 (d, J =

15.6 Hz, IH), 4.86 (m,

IH), 3.97 (m, 4H)

8.43 (s, IH), 7.76 (d, 7

= 2.4 Hz, IH), 7.60 (m,

2H),7.38 (d,7 = 7.6 Hz,

594.67 1H),7.33 (d,7=6.4 Hz,

AC63 77-80 3H), 6.54 (d,7= 16.0 3257, 1653

([M+H]⁺) Hz, IH), 6.46 (m, IH),

6.41 (dd,7= 16.08.0

Hz, 1H),4.65 (d,7 = 6.0

Hz, 2H), 4.15 (m, IH) 7.72 (d, 7=8.0 Hz, IH),

7.44 (s, IH), 7.40 (s,

2H),7.36 (d, 7=6.8 Hz,

1H),7.05 (t, 7 =5.2 Hz,

580.72 IH), 6.70 (t, 7 =5.2 Hz,

AC64 83-85

([M-H]-) IH), 6.57 (d,7= 15.6

Hz, IH), 6.44 (dd, 7 =

15.6, 8.0 Hz, IH), 4.23

(d, 7 = 5.6 Hz, 2H), 4.15

(m, IH), 4.01 (m, 2H)

8.39 (d, 7 = 2.0 Hz,

IH), 8.12 (t, 7 = 8.4 Hz,

IH), 7.71 (d, 7 = 2.4 Hz,

IH), 7.34 (m, 3H), 7.26

534.72 (m, IH), 7.11 (m, 2H), 1658, 1113,

AC65

([M-H]^") 6.59 (d, 7= 16.0 Hz, 817, 2925

IH), 6.46 (dd,7= 16.0,

8.0 Hz, IH), 4.66 (d,7 =

5.2 Hz, 2H), 4.13 (m,

IH)

7.88 (s, IH), 7.63 (d,7 =

1.6 Hz, IH), 7.57 (d, 7 =

8.0 Hz, IH), 7.40 (m,

2H), 6.80 (t, 7 =5.6 Hz,

624.61 IH), 6.70 (t, 7 =5.6 Hz,

AC66 73-75

([M-H]^") IH), 6.56 (d, 7= 16.0

Hz, IH), 6.44 (dd, 7 =

16.0, 8.0 Hz, IH), 4.22

(m, 2H), 4.12 (m, IH),

4.01 (m, 2H)

8.07 (t,7 = 8.0 Hz, IH),

7.34 (d, 7 =6.0 Hz, 2H),

7.28 (s, IH), 7.17(s,

479.82 2H), 6.59 (d, 7= 15.6

AC67 3272, 1644

([M-H]) Hz, IH), 6.46 (dd, 7 =

15.6, 8.0 Hz, IH), 5.49

(m, IH), ,4.12 (m, IH),

3.49 (m, 4H). 8.6 (t, 7=6.4 Hz, IH),

8.45 (m, IH), 7.86 (d, 7

= 6.4 Hz, 2H), 7.75 (t, 7

= 8.0 Hz, IH), 7.63 (d, 7

546.80 = 12.0 Hz, IH), 7.48 (d,

AC68 90-93 3315, 1684

([M-H]-) 7 =8.0 Hz, 1H),7.03

(dd,7= 15.6, 9.6 Hz,

IH), 6.80 (d,7= 15.6

Hz, IH), 4.88 (m, IH),

3.96 (m, 4H)

7.41 (d, 7 =8.0 Hz, IH),

7.34 (d, 7 =5.6 Hz, 2H),

7.26 (m, IH), 7.23 (m,

IH), 6.81 (s, IH), 6.57

542.82 (d,7= 15.6 Hz, IH),

AC69 3294, 1685

([M-H]^") 6.55 (s, IH), 6.39 (dd, 7

= 15.6, 8.0 Hz, IH),

4.18 (m, 2H),4.13(m,

IH), 3.97 (m, 2H), 2.46

(s, 3H)

8.38 (d, 7 = 2.4 Hz, IH),

8.22 (d, 7 =6.8 Hz, 2H),

7.71 (d, 7 = 2.4 Hz, IH),

7.35 (d, 7 =6.0 Hz, 2H),

7.30 (d, 7 = 7.6 Hz, IH),

176- 545.23 7.15 (d, 7= 1.6 Hz, IH),

AC70

178 ([M-H]^") 6.93 (d,7= 1.2 Hz, IH),

6.60 (d,7= 15.6 Hz,

IH), 6.43 (dd,7=15.6,

7.6 Hz, IH), 4.66 (d,7 =

6.0 Hz, 2H), 4.13 (m,

IH), 3.98 (s, 3H)

8.24 (d, 7 = 7.6 Hz, IH),

8.15 (d, 7 =8.4 Hz, IH),

7.35 (d, 7 =6.0 Hz, 2H),

7.13 (d, 7= 1.2 Hz, IH),

492.20 6.92 (s, IH), 6.61 (d,7 = 1639, 3079,

AC71

([M-H]) 16.0 Hz, IH), 6.43 (dd, 858

7= 16.0, 7.6 Hz, IH),

5.48 (m, lH),4.13(m,

IH), 4.03 (s, 3H), 3.48

(m, 4H) 8.42 (d, J = 2.4 Hz, 1H),

7.75 (d, J = 2.4 Hz, 1H),

7.34 (m, 4H), 7.20 (m,

2H), 6.60 (d,7 = 16.0

543.05 Hz, 1H), 6.36 (dd,7 = 1642, 3246,

AC72

([M-H]-) 16.0, 8.0 Hz, 1H), 6.12 814, 1113

(t, 7=5.6 Hz, 1H),4.62

(d, 7 = 6.0 Hz, 2H), 4.20

(m, 1H), 2.82 (m, 2H),

1.45 (t, 7 = 5.6 Hz, 3H)

8.72 (s, 1H), 7.97 (d,7 =

7.2 Hz, 1H), 7.70 (d, 7 =

8.4 Hz, 1H), 7.61 (m,

644.78 2H), 7.40 (m, 2H), 6.55 3431, 1652,

AC75

«M+H]⁺) (m, 2H), 6.42 (dd,7 = 1171,809

16.0, 8.0 Hz, 1H), 4.76

(d, 7 = 6.0 Hz, 2H), 4.12

(m, 1H)

8.87 (t,7 = 6.0 Hz, 1H),

8.34 (d, 7 = 2.1 Hz, 1H),

7.85 (d, 7 =6.3 Hz, 3H),

7.48 (m, 4H), 6.57 (d, 7

531.34 = 15.6 Hz, 1H), 6.45 3120, 1708,

AC76

([M+H]⁺) (dd,7= 15.6, 9.0 Hz, 1171

1H), 4.84 (m, 1H), 4.49

(d, 7 = 5.7 Hz, 2H), 2.82

(m, 2H), 2.36 (t, 7 =5.6

Hz , 3H)

8.87 (t,7 = 6.0 Hz, 1H),

8.34 (d, 7 = 2.1 Hz, 1H),

7.85 (d, 7 =6.3 Hz, 3H),

531.1 7.48 (m, 4H), 6.57 (d, 7

3444, 1648,

AC77 = 15.6 Hz, 1H), 6.45

«M+H]⁺) 1114,814

(dd,7= 15.6, 8.0 Hz,

1H), 4.84 (m, 1H), 4.49

(d,7 = 5.7 Hz, 2H), 2.36

(s, 3H)

8.59 (t, 7 = 6.4 Hz, 1H),

8.47 (t,7 = 5.6 Hz, 1H),

7.89 (s, 2H), 7.45 (m, 3432, 1631,

561.06 3H), 6.87 (m, 1H), 6.75

AC78 1161,840

([M+H]⁺) (d,7= 15.6 Hz, 1H),

4.85 (t,7 = 8.0 Hz 1H),

3.98 (m, 4H), 2.58 (s,

3H) 8.69 (t, 7 = 6.0 Hz, IH),

8.58 (t, 7 = 6.0 Hz, IH),

7.92 (s, IH), 7.87 (d,7 =

610.97 6.4 Hz, 2H), 7.62 (d, 7 =

3303, 1658,

AC79 8.4 Hz, IH), 7.45 (d, 7 =

«M+H]⁺) 1166,817

8.4 Hz, IH), 7.0 (m,

IH), 6.76 (d,7= 15.6

Hz, IH) 4.83 (t, 7=8.0

Hz, IH), 3.98 (m, 4H)

7.37 (m, 3H), 7.26 (m,

IH), 7.24 (m, IH), 6.59

561.06 (d,7= 15.6 Hz, IH),

3412, 1624,

AC80 6.39 (dd, 7= 15.6, 8.0

«M+H]⁺) 1157,825

Hz, IH), 4.24 (m, 4H),

3.90 (m, IH), 2.83 (m,

2H), 1.26 (m, 3H)

8.73 (d,7=5.6 Hz,

IH), 8.45 (t, 7 =6.0 Hz,

IH), 7.76 (s, 3H), 7.45

546.93 (m, 3H), 6.86 (dd, 7 =

AC81 16.0, 9.2 Hz, IH), 4.83

9-92 ([M-H]-) (m, IH), 4.56 (m, 2H),

4.51 (m, IH), 4.10 (m,

2H), 3.85 (d,7=6.0

Hz, 2H), 2.50 (m, 3H)

7.38 (d, 7= 1.8 Hz,

2H), 7.33 (s, IH), 7.27

(s, 3H), 6.58 (d, 7= 16.0

477.69 Hz, IH), 6.42 (d, 7 = 8.1 1646, 1353,

AC82 Hz, IH), 6.36 (dd,7 = 1196, 1112,

«M+H]⁺) 16.0, 7.8 Hz, IH), 4.71 800

(m, IH), 4.23 (m, 3H),

3.26 (m, 2H), 2.45 (s,

3H)

8.07 (t, 7 =8.4 Hz, IH),

7.39 (t, 7= 1.6 Hz, IH),

7.31 (d, 7= 1.2 Hz, IH),

7.26 (m, 2H), 7.23 (m,

493.83 lH),7.19(d,7= 1.6 Hz, 1527, 1113,

AC83 IH), 6.60 (d,7= 16.8 801, 1167,

([M-H]) Hz, IH), 6.49 (dd,7 = 1321

16.8, 7.6 Hz, IH), 4.90

(m, IH), 4.64 (m, 2H),

4.14 (m, 2H),4.10(m,

IH) 8.07 (t, 7 = 8.0 Hz, IH),

7.34 (m, 3H),7.19(d,7

511.75 = 13.2 Hz, IH), 6.60 (d, 1645, 1113,

AC84 7= 16.4 Hz, IH), 6.48 804, 3030,

([M-H]-) (dd,7= 16.4, 8.0 Hz, 1245

IH), 4.88 (m, IH), 4.62

(m, 2H), 4.12 (m, 3H)

8.60 (d, 7 =6.8 Hz, IH),

8.15 (d, 7 =8.4 Hz, IH),

7.35 (d, 7 =6.0 Hz, IH),

523.83 7.15 (d, 7 = 7.2 Hz, IH),

1652, 3039,

AC85 6.94 (s, IH), 6.60 (d,7 =

([M-H]^") 802, 1114

15.6 Hz, IH), 6.44 (dd,

7 = 7.6,7.6 Hz, IH),

4.93 (m, IH), 4.62 (m,

2H),4.13(m, 6H)

7.35 (d, 7 =6.3 Hz, 3H),

7.26 (m, 2H), 7.20 (m,

IH), 6.60 (d,7= 15.9

524.36 Hz, IH), 6.47 (dd, 7 =

3333, 1651,

AC86 15.9, 6.6 Hz, IH), 4.86

«M+H]⁺) 815

(m, IH), 4.65 (m, 2H),

4.13 (m, 3H),2.84 (q,

2.8 Hz, 2H), 1.26 (m,

3H)

8.07 (t,7 = 8.0 Hz, IH),

7.52 (m, 3H),7.19(d,7

495.82 = 13.2 Hz, IH), 6.59 (d,

1623, 1114,

AC87 7= 16.4 Hz, IH), 6.47

([M-H]^") 816

(dd,7= 16.4, 8.0 Hz,

IH), 4.69 (m, IH), 4.23

(m, 3H), 3.29 (m, 2H)

7.43 (m, 2H), 7.27 (m,

2H), 7.23 (m, 2H), 6.58

(d,7= 16.0 Hz, IH),

509.89 6.41 (dd,7= 16.0,7.6

1666, 1166,

AC89 Hz, 1H),4.79 (d,7 =

«M+H]⁺) 1112, 800

5.6 Hz, 2H), 4.14 (m,

IH), 2.48 (s, 3H),

2.18 (m, IH), 1.16 (m,

4H) 8.34 (m, IH), 8.27 (m,

1H),7.60 (d,7 = 1.6 Hz, 1H),7.49 (d, 7=8.0 Hz, 2H), 7.40 (s, 2H), 7.36

656.9 (dd, 7=8.2, 1.7 Hz,

AC90 IH), 6.53 (d, 7= 16.0

([M-H]-) Hz, IH), 6.38 (dd,7 =

15.9, 7.9 Hz, IH), 4.89 (d, 7 = 8.4 Hz, 2H), 4.48 (d, 7 = 9.0 Hz, 2H), 4.11 (m, IH)

8.18 (t, 7 = 5.0 Hz, IH), 7.58 (d, 7= 1.6 Hz, IH), 7.47 (d, 7 =8.0 Hz, IH), 7.40 (s, 2H), 7.34 (dd, 7

640.9 = 8.1, 1.6 Hz, IH), 6.52

AC91

([M-H]^") (m, 2H), 6.37 (dd,7 =

15.9, 7.9 Hz, IH), 4.54 (d, 7 = 4.9 Hz, 2H), 4.12 (m, IH), 3.99 (qd,7 = 8.9, 6.5 Hz, 2H)

9.16 (d, 7= 6.1 Hz, IH), 7.65 (d,7= 1.6 Hz, IH), 7.57 (d, 7 =8.0 Hz, IH), 7.41 (m, 3H), 7.21 (t, 7

640.9 = 5.6 Hz, IH), 6.55 (d, 7

AC92 = 15.9 Hz, IH), 6.41

([M-H]^") (dd,7= 15.9, 7.8 Hz,

1H),4.59 (d,7=5.6 Hz, 2H),4.45 (qd,7=9.0, 6.0 Hz, 2H), 4.12 (q, 7 = 7.2 Hz, IH)

¹³ C NMR (δ)³

169.91,

169.84,

7.52-7.41 (d, 7 = 8.2 Hz, 138.23, IH), 7.39-7.34 (m, IH), 137.41, 7.24-7.17 (d, 7 = 1.8 Hz, 136.84, 2H), 7.02-6.92 (m, 2H), 134.79, 6.90-6.83 (d, 7 = 11.4 134.69, Hz, IH), 6.71 (br s, IH), 131.07,

485.5 6.17 (br s, IH), 6.12- 128.69,

AC93 6.01 (dd, 7 = 11.4, 10.3 127.49,

([Μ+ΗΓ) Hz, IH), 4.44-4.38 (d, 7 127.43,

= 4.2 Hz, IH), 4.35-4.27 126.72, (m, IH), 4.10-3.99 (d, 7 126.61 (q, 7 = = 5.1 Hz, 2H), 2.78-2.67 212.10 Hz), (m, IH), 2.44 (s, 3H), 125.61, 0.88-0.78 (m, 2H), 0.60- 123.76, 47.89 0.45 (m, 2H) (q, 7 = 28.28

Hz), 43.46,

22.65, 19.97,

8.21

8.36 - 8.24 (d, 7 = 2.4

Hz, IH), 7.75 - 7.64 (m,

IH), 7.38 - 7.24 (m,

3H), 7.24 - 7.09 (d, 7 =

1.8 Hz, 2H), 6.99 - 6.90

511.6 3262, 1607,

(m, 2H), 6.89 - 6.74 (d,

AC94 1247, 1164,

([Ml^") 7 = 11.4 Hz, IH), 6.63 - 1111 6.43 (m, IH), 6.14 - 5.98 (m, IH), 4.69 - 4.51 (d, 7 = 6.1 Hz, 2H),

4.37 - 4.20 (m, IH),

2.46 - 2.31 (s, 3H)

7.58 (d, 7 = 7.9 Hz, IH),

7.44 - 7.29 (m, 3H),

7.14 (dd, 7 = 7.9, 1.6

Hz, IH), 6.86 (d, 7 =

626.9 11.4 Hz, IH), 6.76 (t, 7

AC95 48-61

([Μ+Η]⁺) = 5.9 Hz, IH), 6.59 (br

s, IH), 6.21 - 6.04 (m,

1H), 4.23 (d, 7 = 5.5 Hz,

IH), 3.98 (qd, 7 = 9.0,

6.5 Hz, 2H) 8.83 (s, IH), 8.06 (br,

IH), 7.90 (s, 2H), 7.63

(d, J = 8.1 Hz, 2H), 7.53

61 (m, IH), 6.94 (m, IH),

AC96 9.6 6.77 (d, 7 = 15.3 Hz, 1616, 1114

«M+H]⁺) IH), 6.63 (d, 7 = 9.3 Hz,

IH), 4.84 (m, IH), 4.30

(d, 7 = 5.6 Hz, 2H),

2.99 (s, 6H)

8.20 (d, 7 = 2.1 Hz,

IH), 7.73 (d, 7 = 2.7 Hz,

IH), 7.60 (m, 2H), 7.39

(s, 2H), 7.29 (m, IH),

606.6

AC97 6.79 (d, 7 = 8.4 Hz, IH), 1644, 1113

«M+H]⁺)

6.55 (d, 7 = 15.9 Hz,

IH), 6.40 (m, 2H), 4.60

(d, 7 = 2.7 Hz, 2H), 4.13

(m, IH), 3.95 (s, 3H)

9.04 (t, 7 = 6.0 Hz, IH),

8.60 (t, 7 = 6.6 Hz, IH),

8.25 (s, IH), 7.97 (d, 7 =

8.1 Hz, IH), 7.87 (d, 7 =

577.87 6.3 Hz, 2H), 7.69 (d, 7

AC98 1663, 1168

«M+H]⁺) = 7.5 Hz, IH), 7.15 (dd,

7 = 15.9, 9.3 Hz, IH),

6.89 (d, 7 = 15.9 Hz,

IH), 4.86 (m, IH), 3.98

(m, 4H).

8.69 (t, 7 = 6.0 Hz, IH),

8.58 (t, 7 = 6.6 Hz, IH),

7.91 (s, IH), 7.85 (m,

IH), 7.61 (m, 2H), 7.52

574.81

AC99 (m, 2H), 6.98 (dd, 7 = 1650, 1164

«M+H]⁺)

15.3, 9.0 Hz, IH), 6.76

(d, 7 = 15.3 Hz, IH),

4.81 (m, 1H), 4.01 (m,

4H) 8.29 (s, IH), 8.22 (d, 7

= 8.1 Hz, IH), 7.93 (d, J

= 7.8 Hz, IH), 7.72 (m,

IH), 7.65 (m, 2H), 7.40

673.80 (s,2H), 7.18(br, IH),

ACIOO 3403, 1659

«M+H]⁺) 6.59 (d, 7 = 16.0 Hz,

IH), 6.43 (dd, 7=16.0,

7.6 Hz, IH), 5.02 (d,7 =

1.2 Hz, 2H), 4.12 (m,

IH)

7.56 (d, 7=9.0 Hz,

1H),7.39 (d, 7=6.0

Hz, 2H), 7.26 (m, 2H),

6.54 (d, 7= 15.9 Hz,

636.83 IH), 6.37 (dd, 7 = 8.0,

AC101 1637, 1113

«M+H]⁺) 15.9 Hz, IH), 4.01 (m,

IH), 3.84 (m, 2H), 3.33

(m, 2H), 3.04 (m, 2H),

2.84 (m, 3H), 2.62 (m,

IH)

7.60 (m, 2H), 7.32 (m,

IH), 7.03 (d, 7 = 7.2 Hz,

2H), 6.74 (br, IH), 6.62

592.84 (br, IH), 6.56 (d,7 =

AC102 16.2 Hz, IH), 6.41 (dd, 1668, 1167

([M+H]⁺) 7= 16.2, 7.8 Hz, IH),

4.22 (d, 7 =5.4 Hz,

2H),4.14(m, IH), 4.01

(m, 2H)

8.40 (d, 7 = 8.0 Hz, IH),

7.92 (d, 7 = 5.2 Hz, IH),

7.59 (d, 7 = 8.0 Hz, IH),

7.35 (d, 7 = 8.0 Hz, IH),

6.99 (dd,7= 16.0,7.6

Hz, IH), 6.76 (d,7 =

612.7 16.0 Hz, IH), 4.84 (m,

99.2- 1634, 1113,

AC103 «M+H]⁺) 1H),4.23 (d,7= 13.2

105.0 809

Hz, IH), 3.97 (m, IH),

3.79 (d,7= 13.6 Hz,

IH), 3.16 (t, 7= 11.2

Hz, IH), 2.77 (t, 7 =

11.2 Hz, IH), 1.99 (s,

3H), 1.88 (m, 2H), 1.45

(m, 2H) 7.60 (m, 2H), 7.40 (m

3H), 6.55 (d, 7 = 15.6 3437, Hz, IH), 6.41 (dd, 7 = 1644,

680.97 15.6, 7.8 Hz, IH), 4.24

AC104 1113,

«M+H]⁺) (m, IH), 3.34 (m, 2H),

2.90 (m, IH), 2.24 (m, 807, 2H), 1.52(m, 2H), 1.34 511

(m, 4H)

7.59 (s, IH), 7.55 (m,

IH), 7.50 (m, 1H),7.40

(m, 2H), 6.54(d, 7 =

3303, 1649,

609.9 16.0 Hz, IH), 6.50 (7 =

AC105 1115, 2242,

«M+H]⁺) 16.0, 8.0 Hz, IH), 4.14

809, 506 (m, 2H), 3.08 (m, 4H),

2.67 (m, 2H), 2.12 (m,

2H), 1.70 (m, 2H).

7.59 (s, IH), 7.51 (d, 7 =

8.4 Hz, IH), 7.40 (s,

2H), 7.36 (d, 7 = 6.8 Hz,

IH), 6.54 (d, 7 = 16.0 3417,

584.95 Hz, IH), 6 .40 (dd, 7 = 1648,

AC106 16.0, 8.0 Hz, IH), 6.03

«M+H]⁺) (d, 7 = 8.0 Hz, IH), 4.11 1112,

(m, 2H), 3.10 (m, 2H), 805, 555 2.50 (m, 2H ), 2.50 (s,

3H) (m, 2H ), 1.94 (m,

2H)

8.41 (d, 7 = 7.8 Hz, IH),

7.90 (s, 2H), 7.62 (m,

2H), 7.51(m, IH), 6.92 3303, (dd, 7 = 15.9, 9.0 Hz, 1645, IH), 6.77 (d, 7 = 15.9

609.9 Hz, IH), 4.81 (m, IH), 1115,

AC107

([M+H]⁺) 3.73 (s, 2H), 3.31 (m, 2243,

IH), 3.28 (m, IH), 2.82

(t, 7 = 11.4 Hz, 2H), 810, 2.82 (m, 2H), 2.30 (m, 507 2H), 1.88 (m, 2H), 1.57

(m, 2H) 7.60 (m, 2H) 7.39 (s,

2H), 7.28 (m, IH), 6.56 3420, (d,7 = 15.6 Hz, IH), 1649, 6.40 (dd,7 = 15.6,7.8

626.9 Hz, IH), 5.91 (m, IH), 1113,

AC108

([M+H]⁺) 4.65 (m, 2H),4.10(m, 809,

IH), 4.07 (m, 2H), 3.59

(m, IH), 2.74 (m, 2H), 554 2.13 (m, 4H), 2.07 (m,

IH)

7.56 (m, 2H), 7.39 (s,

2H), 7.29 (s, IH), 6.50

(d, 7=15.9 Hz, IH),

6.41 (dd,7 = 15.9, 8.0

614.6

AC109 Hz IH), 4.09 (m, IH), 1647, 1113

«M+H]⁺)

3.88 (m, 2H), 3.49 (m,

2H),2.92 (m, 2H), 2.81

(m, IH), 2.74 (m, 2H),

2.25 (m, 4H)

11.20 (s, IH), 8.66 (br,

IH), 7.92 (m, 3H), 7.62

(d, 7 = 8.0 Hz, IH), 7.45

572.6 (d, 7 = 8.0 Hz, IH), 6.77 3412, 1690,

AC110 (dd,7= 15.6, 9.2 Hz, 1114, 846,

([M+H]⁺) IH), 6.77 (d,7= 15.6 559

Hz, IH), 4.85 (m, IH),

3.74 (d, 7 =5.2 Hz, 2H),

3.61 (s, 3H)

8.63 (t,7 = 6.0 Hz, IH),

8.04 (t,7 = 6.0 Hz, IH),

7.92 (m, 3H), 7.62 (d, 7

= 1.2 Hz, IH), 7.47 (d, 7

= 7.6 Hz, IH), 7.00 (dd,

582.79 7= 15.6, 8.8 Hz, IH), 3419, 1659,

AC111

([M+H]⁺) 6.77 (d, 7= 15.6 Hz, 843, 557

IH), 5.19 (d, 7= 1.6 Hz,

IH), 5.01 (d, 7= 1.2 Hz,

IH), 4.85 (m, IH), 3.86

(d, 7 = 5.6 Hz, 2H), 3.75

(t,7=5.6 Hz, 2H) 8.84 (br, IH), 8.58 (m,

IH), 8.30 (m, IH), 7.91

(s,2H), 7.61 (d, 7=8.1

Hz, IH), 7.42 (d, 7 = 7.8

582.79 Hz, IH), 7.00 (dd, 7 = 3399, 1662,

AC112 15.6, 9.3 Hz, IH), 6.77 1114, 807,

«M+H]⁺) (d,7= 15.6 Hz, IH), 582

4.85 (m, 1H),4.11 (d, 7

= 5.6 Hz, IH), 3.73 (d,

7 = 5.6 Hz, IH), 3.04 (s,

6H)

8.48 (t, 7 = 5.2 Hz, IH),

8.3 (s, IH), 7.90 (s, 2H),

7.79 (dd, 7 = 2.0, 2.0 Hz

2H),7.58(d,7=8.4 Hz,

626.88

1H)7.46 (d, 7 = 7.6 Hz, 3431, 1651,

AC113 ([M+H]⁺) 1H)7.26 (d, 7 = 7.6 Hz, 1113,808,

IH), 6.98 (m, IH), 6.75 554

(d,7= 15.6 Hz, IH),

4.85 (m, IH), 3.49 (d, 7

= 6.4 Hz, 2H) 2.87 (t, 7

= 6.4 Hz, 2H)

8.77 (s, IH), 8.58 (d, 7 =

7.2 Hz, 2H), 7.93 (d,7 =

7.2 Hz, 2H), 7.60 (dd, 7

= 1.2, 0.8 Hz, IH), 7.37

113.7- 570.7 (d, 7 = 7.6 Hz, IH), 6.99

AC114

117.5 ([M+H]⁺) (m, IH), 6.77 (d,7=16

Hz, IH), 4.85 (m, IH),

4.10 (m, 1H)3.29 (m,

2H), 3.05 (m, 2H), 2.0

(m, 2H), 1.76 (m, 2H)

8.43 (s, IH), 7.79 (d,7 =

8.0 Hz, IH), 7.51 (m,

1H),7.36 (d,7=8.4 Hz,

529.00 3H), 7.21 (m, 3H), 6.55

1589, 3459,

AC115 (d,7= 15.6 Hz, IH),

«M+H]⁺) 801, 1110

6.36 (dd, 7= 15.6, 8.0

Hz, IH), 5.04 (d,7 = 5.6

Hz, 2H), 4.10 (m, IH),

2.35 (s, 3H) 7.99 (d, 7=8.4 Hz, IH),

7.46 (d, 7 = 1.6 Hz, IH),

7.34 (d, J =6.4 Hz, 2H),

614.87 7.28 (m, 2H), 6.62 (m, 3424, 1657,

AC116

([M+H]⁺) 2H), 6.47 (dd,7 = 16.0, 1165

7.2 Hz, IH), 4.23 (m,

2H),4.12 (m, IH), 4.00

(m, 2H)

8.39 (br, IH), 7.85 (br,

IH), 7.62 (m, 3H), 7.53

(d, 7 = 8.0 Hz, IH), 7.46

(s, IH), 7.40 (d, 7=8.0

525.42 Hz, IH), 7.17 (m, IH), 3401, 1636,

AC117

([M-H]-) 6.78 (dd, 7= 16.0, 8.8 1113,750

Hz, IH), 6.70 (m, IH),

4.77 (m, IH), 4.66 (s,

IH), 4.32 (s, IH), 2.97

(s, 3H), 2.16 (s,3H)

7.36 (d, 7 =8.0 Hz, 2H),

7.27 (m, 2H), 7.22 (m,

2H), 6.57 (d,7= 16.0

Hz, IH), 6.38 (dd,7 =

471.79 16.0, 8.0 Hz, IH), 6.10 3437, 1655,

AC118 (br, 1H),4.15 (m,2H), 1262, 1105,

([M+H]⁺) 3.89 (m, IH), 3.80 (m, 802

2H), 3.35 (m, IH), 2.46

(s, 3H), 2.06 (s,lH),

1.96 (m, 2H), 1.65 (m,

IH)

7.39 (s,2H), 7.25-7.18

(m, 3H), 6.58 (d, 7 =

16.0 Hz, IH), 6.30 (dd,

492.17 7= 16.0, 8.4 Hz, IH), 3211, 1569,

BCl

([M+H]⁺) 5.91-5.70 (br, 2H), 1113,806

4.05 (m, IH), 3.05 - 2.80 (m, 6H), 2.70 (m,

IH), 1.81 (m, IH) 8.80 (s, IH), 8.20 (s,

IH), 7.82 (m, 3H), 7.4

(s,2H), 6.62 (d, 7=16.0

Hz, IH), 6.52 (dd, / =

506.4 2923, 1542,

BC2 16.0, 8.0 Hz, IH),

«M+H]⁺) 1033, 805

4.18(m, IH), 3.38 (m,

2H),2.98 (m, 2H), 2.71

(m, IH), 2.04 (m, 2H),

1.54 (s, 3H).

7.40 (s, 2H), 7.33-7.22

(m, 3H), 6.61 (d,/ =

16.0 Hz, IH), 6.34 - 6.28 (dd,/= 16.0, 8.0

518.04 3120, 1592,

BC3 Hz, IH), 5.96-5.80 (m,

([M-H]-) 1146, 895

3H), 5.22 (m, 4H), 4.01

(m, 2H), 2.84 - 2.99 (m,

2H), 2.71 (m, IH), 1.86

(m, IH)

7.39 (s, 2H), 7.25-7.20

(m, 3H), 6.34 (d,/ =

16.0 Hz, IH), 6.30 (dd, J

= 16.0, 8.0 Hz, IH),

529.02 5.81 (br, IH), 5.48 (m, 3283, 1652,

BC4

([M+H]⁺) 1H),4.10 (m, IH), 3.10 1241,811

(m, 2H), 2.86-3.07 (m,

2H),2.86 (m, IH), 1.81

(m, IH);

7.40 (s, 2H), 7.21 (s,

1H),7.12 (m, IH), 6.56

(d,/= 16.0 Hz, IH),

6.32 (dd,/ = 16.0, 8.4

Hz, IH), 5.85 (brs, IH), 3489, 3291,

544.25

BC5 5.23 (brs, IH), 4.12 (m, 1655, 1112,

([M-H])

IH), 3.18 (m, 3H), 2.80 808 (m, 3H), 2.08 (m, 2H),

1.83 (m, 5H), 1.25 (m,

2H), 1.01 (m, 3H), 0.78

(m, 2H) 7.40 (s,2H), 7.31-7.18

(m, 3H), 6.58 (d,/ =

16.0 Hz, IH), 6.24 - 6.28 (dd,/= 16.0, 8.0

485.96 Hz, IH), 5.40 (br, IH), 3429, 1114,

BC6

([M-H]-) 4.01 (m, 2H), 2.78 - 804

3.01 (m, 2H),2.51 (s,

IH), 1.86 (m, IH), 1.20

(m, 2H), 1.01 (m, 2H),

0.78 (m, 2H)

7.40 (s,2H), 7.31 (s,

IH), 7.18 (m, IH), 7.18

(s, IH), 6.58 (d,/= 16.0

Hz, IH), 6.32 (dd, / =

16.0, 8.0 Hz, IH), 5.78

500.01 3296, 1115,

BC7 (brs, IH), 5.21 (br s,

([M-H]^") 806

IH), 4.01 (m, IH), 2.78

(m, 2H), 2.01 (m, IH),

1.86 (m, 4H), 1.25 (m,

2H), 1.01 (m, 3H), 0.78

(m, 2H)

7.38-7.20 (m, 5H), 6.62

(d,/= 16.0 Hz, IH),

6.34 (dd,/= 16.0, 8.0

511.88 Hz, IH), 5.83 (br, IH), 1657, 1113,

BC8

([M-H]^") 5.52 (m, lH),4.12(m, 855

IH), 3.12 (m, 2H), 3.06- 2.82 (m, 2H), 2.75 (m,

IH), 1.85 (m, IH)

8.30 (s, IH), 7.68 (d,/ =

6.4 Hz, IH), 7.38-7.20

(m, 5H), 6.60 (d,/ =

16.0 Hz, IH), 6.34 (dd,

179- 556.83 /= 16.0, 8.0 Hz, IH),

BC9

181 ([M-H]) 5.63 (br, IH), 5.52 (m,

1H),4.12 (m, IH), 3.56

(s, 2H), 3.06-2.82 (m,

2H), 2.70 (m, IH), 1.82

(m, IH) 7.38-7.20 (m, 5H), 6.62

(d,7 = 16.0 Hz, IH),

6.34 (dd,7 = 16.0, 8.0

497.98 Hz, IH), 5.83 (br, IH),

3027, 1654,

BC10 5.52 (m, lH),4.12(m,

([M-H]-) 815

IH), 3.02 (m, 3H), 2.82

(m, IH), 2.50 (m, 3H),

1.82 (m, IH), 1.42 (m,

IH)

7.80 (m, IH), 7.48 (m,

2H),7.326.65 (d,7 =

530.09 16.0 Hz, IH), 6.54 (dd,

([M 7 = 16.0, 8.0 Hz, IH), 1715, 1113,

BC11 -H]^")

5.38 (m, lH),4.18(m, 816 IH), 3.62 (m, IH), 3.32

(m, IH), 2.86 (m, IH),

1.81 (m, IH)

7.32, (d, 7 = 6.0 Hz, 2H)

7.28 (m, IH), 7.20 (d, 7

= 8.0, IH), 7.14 (d, 7 =

8.8, IH), 6.70 (d,7 =

514.86 8.0 Hz, IH), 6.60 (m, 3428, 1112,

BC12

«M+H]⁺) 2H),4.15 (m, IH), 3.85 857

(m, IH), 3.65 (m, IH),

3.46 (m, 2H), 3.19 (m,

2H);

8.33 (br, IH), 7.59 (s,

553.06 IH), 7.45 (m, 3H), 6.72

121-

BC13 ([M-H]) (d, 7 = 3.6, IH) ,6.39

126

(m, IH), 4.71 (t, 7 = 7.2

Hz, 2H), 4.15 (m, 2H)

8.83 (t,7 = 6.6 Hz, IH),

8.42 (t, 7= 14.7 Hz,

IH), 8.22 (d, 7= 8.1

Hz, IH), 8.13 (t,7=6.3

172- 554.0

BC14 Hz, IH), 7.98-7.86 (m,

175 ([M-H]^") 2H), 7.16-7.07 (m,

IH), 7.01 - 6.93 (m,

IH), 4.96 -4.81 (m,

3H), 4.00 - 3.88 (m, 2H) 7.37 (m, 3H), 7.28 (m,

4H), 6.60 (d,7 = 16.0 Hz, IH), 6.36 (dd,7 =

107- 402.00

CCl 16.0, 8.0 Hz, IH), 5.75

109 ([M+H]⁺)

(brs, 1H),4.46 (d,7=6 Hz, 2H), 4.01 (m, IH), 2.11 (s, 3H)

7.37 (m, 3H), 7.28 (m, 4H), 6.60 (d,7 = 16.0 Hz, IH), 6.35 (dd,7 =

118- 428.11 16.0, 8.0 Hz, IH), 5.83

CC2

120 ([M+H]⁺) (brs, 1H),4.46 (d,7 =

6.0 Hz, 2H), 4.11 (m, IH), 1.40 (m, IH), 1.02 (m, 2H), 0.77 (m, 2H)

7.38 (m, 3H), 7.27 (m, 3H), 6.60 (d,7 = 16.0 Hz, IH), 6.36 (dd,7 =

119- 468.20 16.0, 8.4 Hz, IH), 5.00

CC3

122 ([M-H]) (brs, 1H),4.48 (d,7 =

5.6 Hz, 2H), 4.11 (m, IH), 3.15 (q, 7=10.4 Hz, 2H)

7.37 (m, 3H), 7.28 (m, 3H), 6.60 (d,7 = 16.0 Hz, IH), 6.35 (dd,7 = 16.0, 8.0 Hz, IH), 5.69

414.16

CC4 (brs, 1H),4.46 (d,7 =

([M-H]^")

6.0 Hz, 2H), 4.21 (m, 1H),2.29 (q, 7=5.8 Hz, 2H), 1.30 (t, 7 = 7.2 Hz, 3H)

7.40 (m, 3H), 7.28 (m, 2H), 6.60 (d,7= 15.6 Hz, IH), 6.33 (dd,7 =

460.28 15.6, 8.0 Hz, IH), 5.84

CC5

([M-H]^") (brs, 1H),4.46 (d,7 =

5.6 Hz, 2H), 4.10 (m, IH), 1.36 (m, IH), 1.02 (m, 2H), 0.77 (m, 2H) 7.40 (m, 3H), 7.26 (m,

IH), 6.60 (d,7 = 16.0

Hz, IH), 6.34 (dd, 7 =

106- 504.08 16.0, 8.0 Hz, IH), 5.96

CC6

108 ([M-H]-) (brs, 1H),4.49 (d,7 =

5.6 Hz, 2H), 4.10 (m,

IH), 3.15 (q, 7=10.8

Hz, 2H)

7.42 (m, 4H), 7.24 (m,

2H), 6.53 (d, 7=16.0

Hz, IH), 6.36 (dd,7 =

127- 436.03

CC7 16.0, 8.0 Hz, IH) , 5.86

128 ([M+H]⁺)

(brs, 1H),4.51 (d,7 =

6.0 Hz, 2H), 4.05 (m,

IH), 2.02 (s, 3H)

8.58 (t, 7 = 5.6 Hz, IH),

7.72 (m, IH), 7.66 (m,

3H),7.49 (d,7=8.0 Hz,

1H),7.30 (d,7=8.0 Hz,

129- 462.15 IH), 6.90 (dd,7= 16.0,

CC8

131 ([M+H]⁺) 8.0 Hz, IH), 6.73 (d,7 =

16 Hz, IH), 4.81 (m,

1H),4.33 (d,7=6.0 Hz,

IH), 1.64 (m, IH), 0.68

(m, 4H)

7.41 (m, 3H), 7.26 (m,

3H), 6.54 (d,7= 16.0

Hz, IH), 6.37 (dd, 7 =

132- 504.25

CC9 16.0, 8.0 Hz, IH), 6.13

134 ([M+H]⁺)

(brs, 1H),4.56 (d,7 =

6.0 Hz, 2H), 4.11 (m,

IH), 3.13(m, 2H)

7.38 (m, 4H), 6.56 (d, 7

= 16.0 Hz, IH), 6.38

538.03

(dd,7= 16.0, 8.0 Hz, 1651, 1112,

CC10 ([M+2H]⁺

IH), 6.18 (m, IH), 4.58 807

) (m, 2H), 4.08 (m, IH),

3.08 (m, 2H) 7.42 (m, 3H), 7.24 (m,

IH), 6.54 (d,/ = 15.6

Hz, IH), 6.34 (dd, / =

111— 494.12 16.0, 8.0 Hz, IH), 6.03 ecu 112 ([M-H]-) (m, IH), 4.53 (d, 7=6.0

Hz, IH), 4.10 (m, IH),

1.39 (m, IH), 1.00 (m,

2H), 0.77 (m, 2H)

7.39 (s,4H), 7.34 (d,/ =

8.0 Hz, IH), 7.26 (m,

IH), 6.57 (d,/ = 16.0

510.07 Hz, IH), 6.35 (dd,/ =

CC12 76-78

([M-H]) 16.0, 8.0 Hz, IH), 6.10

(brs, 1H),4.49 (d, / =

6.0 Hz, 2H), 4.10 (m,

IH), 1.20 (s, 9H)

8.51 (d, 7=5.2 Hz, IH),

7.63 (s, IH), 7.51 (m,

IH), 7.45 (m, 2H), 7.39

563.37 (s, 2H), 7.28 (m, IH),

CC13 73-76

([M-H]) 6.58 (m, 2H), 6.37 (dd, J

= 16.0, 8.0 Hz, IH),

4.71 (d, 7=6.0 Hz, IH),

4.11 (m, IH)

8.51 (m, IH), 8.30 (d, /

= 2.4 Hz, IH), 7.73 (m,

1H),7.61 (s, 2H),7.51

581.45 (s, IH), 7.32 (m, 3H),

3430, 1656,

CC14 ([M+1H]⁺ 6.66 (d,/= 16.0 Hz,

1109,806

) IH), 6.56 (dd,/= 16.0,

8.4 Hz, IH), 4.50 (m,

1H),4.45 (d, 7=5.6 Hz,

IH), 3.56 (s, 2H)

7.40 (m, 3H), 7.33 (m,

IH), 7.22 (m, 2H), 6.54

(d,/= 15.6 Hz, IH),

6.34 (dd,/= 16.0, 8.0 3293, 1651,

480.24

CC15 Hz, IH), 6.03 (br s, IH), 1543, 1114,

«M+H]⁺)

4.53 (d, 7=6.0 Hz, 2H), 812 4.13 (m, IH), 1.41 (m,

IH), 1.00 (m, 2H), 0.77

(m, 2H) 7.42 (s, IH), 7.37 (m,

3H), 7.22 (m, IH), 6.54

(d,7 = 16.0 Hz, IH),

520.33 6.36 (dd, 7 = 16.0, 8.0 3307, 1665,

CC16

([M-H]) Hz, IH), 6.19 (brs, IH), 1114,813

4.51 (d, 7=6.0 Hz, 2H),

4.21 (m, IH), 3.33 (m,

2H)

7.51 (m, 2H),7.39(m,

2H), 7.24 (m, 2H), 6.52

(d,7 = 15.6 Hz, IH),

6.38 (dd, 7 = 15.6,7.6

117- 459.83 3293, 1633,

CC17 Hz, IH), 6.02 (br s, IH),

119 ([M-H]^") 1110, 820

4.53 (d, 7=6.0 Hz, 2H),

4.14 (m, IH), 1.38 (m,

IH) ), 1.00 (m, 2H),

0.77 (m, 2H)

7.48 (m, 2H), 7.41 (s,

1H),7.36 (d, 7=8.0 Hz,

IH), 7.23 (m, 2H), 6.52

(d,7= 16.0 Hz, IH),

119- 501.88 3435, 1644,

CC18 6.39 (dd, 7= 16.0, 8.0

123 ([M-H]^") 1111,817

Hz, IH), 6.13 (brs, IH),

4.56 (d, 7 =6.0 Hz, 2H),

4.15 (m, IH), 3.13(m,

2H)

7.41 (m, 2H), 7.24 (m,

IH), 6.53 (d, 7= 16.0

Hz, IH), 6.35 (dd,7 =

530 3435, 1644,

CC19 16.0, 8.0 Hz, IH), 4.53

«M+H]⁺) 1111,817

(m, 2H), 4.10 (m, IH),

3.42 (m, 2H), 2.97 (s,

3H), 2.78 (m, 2H)

7.42 (m, 3H), 7.24 (m,

IH), 6.54 (d,7= 15.6

Hz, IH), 6.34 (dd, 7 =

512 15.6, 8.0 Hz, IH), 6.03 3293, 1633,

CC20

«M+H]⁺) (m 1H),4.53 (d, 7=6.0 1110, 820

Hz, IH), 4.10 (m, IH),

1.19 (m, IH), 1.00 (m,

2H), 0.77 (m, 2H) (DMSO- ) 8.62 (m,

IH), 7.95 (s, IH), 7.85

(m, IH), 7.66 (m, 3H),

7.47 (d, 7= 8.0 Hz, IH),

493.99

CC21 55-58 6.98 (dd, 7=16.0, 8.0

([M-H]-)

Hz, IH), 6.84 (d,7 =

16.0 Hz, IH), 4.83 (m,

1H),4.44 (s, 2H), 1.68

(m, IH), 0.71 (m, 4H)

8.62 (m, IH), 7.90 (s,

3H), 7.82 (m, IH), 7.45

(m, IH), 6.98 (m, IH),

530.01

CC22 67-69 6.84 (d,7 = 16.0 Hz,

«M+H]⁺)

IH), 4.82 (m, IH), 4.4

(s, 2H), 1.66 (m, IH),

0.72 (m, 4H)

9.02 (br s, IH), 8.54 (br

s, IH), 8.26 (br s, IH),

7.48-7.54 (m, 3H),

564.99 7.22-7.42 (m, 3H),

CC23 69-71

([M-H]) 6.59 - 6.62 (m, 2H),

6.38-6.42 (m, IH),

4.82 (m, 2H),4.19(s,

IH)

7.64 (s, IH), 7.54 (s,

2H), 7.46 (s, 2H), 6.62

(d,7 = 16.0 Hz, IH),

125- 570.26 6.41 (dd,7 = 16.0, 8.4

CC24

127 ([M-H]^") Hz, IH), 6.03 (m, IH),

4.65 (d, 7=6.4 Hz, 2H),

4.14 (m, IH,), 3.13 (q, 7

= 10.6 Hz, 2H)

7.60 (s, IH), 7.40 (s,

2H),7.37 (d, 7=8.0 Hz,

1H),7.31 (d, 7=8.0 Hz,

IH), 6.53 (d, 1H,7 =

579.86 16.0 Hz), 6.35 (dd,7 = 3297, 1663,

CC25

([M-H]^") 16.0, 8.0 Hz, IH), 6.17 1114, 809

(brs, 1H),4.56 (d,7 =

6.4 Hz, 2H), 4.12 (m,

IH), 3.15 (q, 7= 10.6

Hz, 2H) 7.59 (s, IH), 7.39 (m,

2H), 7.30 (s, IH), 6.53

(d,/ = 16.0 Hz, IH),

6.35 (dd,/ = 16.0, 8.0

129- 539.89

CC26 Hz, IH), 6.06 (br s, IH),

131 ([Μ+ΗΓ)

4.42 (d, 7=4.4 Hz, 2H),

4.12 (m, IH), 1.35 (brs,

IH), 0.95 (br s, 2H),

0.75 (m, 2H)

7.39 (s,2H), 7.33 (t,/ =

7.6 Hz, IH), 7.14 (m,

2H), 6.56 (d,/ = 16.0

519.95 Hz, IH), 6.35 (dd,/ =

CC27 16.0, 7.6 Hz, IH), 6.06 3306, 1786

([M-H]) (brs, 1H),4.52 (d,/ =

16.0 Hz, 2H), 4.08 (m,

IH), 3.90 (s, 2H), 3.13

(m, 2H)

7.39 (s, 2H), 7.35 (m,

1H),7.14 (m, 2H), 6.55

(d,/ = 15.6 Hz, IH),

477.93 6.33 (dd,/ = 15.6, 8.0 3625, 1747

CC28 Hz, IH), 5.93 (brs, IH),

([M-H]^") 4.49 (d,/ = 16.0 Hz,

2H),4.10 (m, IH), 1.36

(m, IH), 1.00 (m, 2H),

0.77 (m, 2H)

8.58 (d, 7 = 4.6 Hz, IH),

7.74 (m, IH), 7.62 (m,

2H), 7.52 (m, IH), 7.4

(s, 2H), 7.3 (m, IH), 7.2

(m, 2H), 6.60 (d,/ =

620.86 16.0 Hz, IH), 6.38 (dd, 1645, 1115,

CC29

([M-H]^") /= 16.0, 8.0 Hz, IH), 808

5.02 (s, IH), 4.8 (s, IH),

4.8(d,/= 10 Hz, 2H),

4.10 (m, IH), 1.8 (m,

IH), 1.2 (m, 2H),0.6

(m, 2H) 7.41 (m, 4H), 7.24 (m,

IH), 6.53 (d, 7 = 16.0

Hz, IH), 6.35 (dd, 7 =

16.0, 8.0 Hz, IH), 6.12

101- 559.75

CC30 (br s, IH), 4.53 (m, 2H),

104 ([M-H] ) 4.10 (m, IH), 3.42 (m,

2H), 2.91 (s, 3H), 2.78

(m, 2H)

7.58 (m, 2H), 7.41 (m,

3H), 7.24 (m, IH), 6.53

(d, 7 = 16.0 Hz, IH),

6.35 (dd, 7 = 16.0, 8.0

177- 463

CC31 Hz, IH), 4.70 (br s, IH),

178 ([M-H]^") 4.43 (s, 2H), 4.08 (m,

IH), 3.21 (m, 2H), 1.25

(m, 3H);

7.66 (m, 2H), 7.54 (m,

IH), 7.41 (s, 2H), 6.62

(d, 7 = 16.0 Hz, IH),

141- 532.99

CC32 6.40 (dd, 7 = 16.0, 8.0

142 «M+H]⁺)

Hz, IH), 4.59 (s, 3H),

4.19 (m, IH), 3.25 (m,

2H), 1.15 (m, 2H)

7.57 (s, IH), 7.40 (m,

2H), 7.30 (s, IH), 7.20

(br s, IH), 6.53 (d, 7 =

16.0 Hz, IH), 6.33 (dd,

3338, 1631,

540.88 7 = 16.0, 8.0 Hz, IH),

CC33 1578, 1114,

([M-H]^") 6.06 (br s, IH), 4.75 (br

809 s, IH), 4.42 (s, 2H), 4.20

(br s, IH), 4.15 (m, 2H),

3.20 (m, 2H), 1.15 (m,

3H)

7.42 (m, 3H), 7.28 (m,

2H), 6.54 (d, 7 = 16.0

Hz, IH), 6.36 (dd, 7 =

118- 541.40 16.0, 8.0 Hz, IH), 4.96

CC34

120 «M+H]⁺) (m, IH), 4.51 (d, 7 = 5.6

Hz, 2H), 4.12 (m, IH),

3.69 (t, 7 = 4.8 Hz, 4H),

3.35 (t, 7 = 4.8 Hz, IH) 9.95 (brs, IH), 8.17 (d,

7 = 4.8 Hz, IH), 7.61 (d,

J =6.4 Hz), 7.43 (m,

3H), 7.24 (m, 2H), 6.90

547.82 (t, 7=5.6 Hz, IH), 6.66

CC35 78-79

([Μ+ΗΓ) (d, 7 =8.4 Hz, IH), 6.54

(d,7= 16.0 Hz, IH),

6.33 (dd,7= 16.0, 8.0

Hz, 1H),4.65 (d,7=6.0

Hz, IH), 4.09 (m, IH)

7.39 (m, 4H), 7.28 (m,

IH), 6.54 (d,7= 16.0

Hz, IH), 6.34 (dd, 7 =

497 16.0, 8.0 Hz, IH), 4.97 3350, 1705,

CC36

([M-H]-) (brs, 1H),4.38 (d,7 = 1114, 808

6.0 Hz, 2H), 4.10 (m,

IH), 2.9 (s, 3H), 2.7 (s,

3H)

7.49 (d,7=8Hz, IH),

7.41 (d, 7 = 7.2 Hz, 2H),

7.26 (m, 2H), 6.50 (d, 7

= 16 Hz, IH), 6.35 (dd,

515.01

CC37 88-91 7= 16.0, 8.0 Hz, IH),

«M+H]⁺)

6.0 (brs, IH), 5.73 (brs,

IH), 4.80 (br s, 2H),

4.09 (m, IH), 1.23 (m,

3H)

7.48 (d,7=8Hz, IH),

7.39 (m, 3H), 7.27 (m,

IH), 6.54 (d,7= 16 Hz,

IH), 6.33 (dd,7=6.0,

526.97 8.0Hz, IH), 6.17 (brs,

CC38 63-66

([M+H]⁺) IH), 5.92 (br s, IH),

5.83 (m, 2H), 5.29 (t, 7

= 15.4 Hz, 2H), 4.80 (br

s, 2H), 4.12 (m, IH),

4.02 (br s, 2H)

7.39 (m, 4H), 7.28 (m,

IH), 6.54 (d,7= 16.0

Hz, IH), 6.34 (dd, 7 =

526.09 3350, 1705,

CC39 16.0, 8.0 Hz, IH), 4.97

([M-H]^") 1114, 808

(brs, 1H),4.38 (d,7 =

6.0 Hz, 2H), 4.10 (m,

IH), 1.53 (s, 9H) 7.46 (m, 5H), 7.29 (m,

IH), 7.20 (m, 3H), 6.55

(d, 7 = 16.0 Hz, IH),

159- 580.25

CC40 6.37 (dd, 7 = 16.0, 8.0

160 ([M-H] )

Hz, IH), 5.62 (br s, IH),

4.55 (d, J = 6.4 Hz, 2H),

4.11 (m, IH)

7.48 (m, IH), 7.43 (m,

3H), 7.38 (m, IH), 7.23

(s, IH), 6.55 (d, 7 = 16.0

512.22 1740, 1701,

CC41 Hz, IH), 6.36 (d, 7 =

([M-H] ) 1114, 808

16.0 Hz, IH), 4.60 (d,

2H), 4.18 (m, IH), 3.85

(s, 3H)

(DMSO- ) 9.45 (br s,

2H), 7.90 (s, 2H), 7.75

(s, IH), 7.46 (br s, IH),

161- 578.96

CC42 7.28 (br s, IH), 6.93 (m,

163 ([M-H]^")

IH), 6.75 (br s, IH),

4.80 (m, IH), 4.40 (br s,

2H), 3.90 (br s, 2H)

8.11 (d, 7 = 4.0 Hz, IH),

7.40 (m, 5H), 7.22 (m,

140- 505.39 IH), 6.61 (m, 2H), 6.35

CC43

142 «M+H]⁺) (m, 2H), 4.94 (br s, IH)

4.61 (d, 7 = 6.4 Hz, 2H),

4.11 (m, IH)

8.41 (s, IH), 7.77 (s,

IH), 7.47 (br s, IH),

7.40 (s, 2H), 6.58 (d, 7 =

536.88 16.0 Hz, IH), 6.45 (dd, 3320, 1674,

CC44

([M-H] ) 7 = 16.0, 8.0 Hz, IH), 1114, 808

4.68 (d, 7 = 4.0 Hz, 2H),

4.14 (m, IH), 3.24 (q, 7

= 10.8 Hz, 2H)

8.41 (s, IH), 7.76 (s,

1H), 7.40 (s, 2H), 7.15

(br s, IH), 6.58 (d, 7 =

494.88 16.0 Hz, IH), 6.44 (dd,

3309, 1659,

CC45 7 = 16.0, 8.0 Hz, IH),

([M-H]^") 1115, 808

4.67 (d, 7 = 4.4 Hz, 2H),

4.16 (m, IH), 1.57 (m,

IH), 1.04 (m, 2H), 0.87

(m, 2H) 8.06 (m, IH), 7.61 (m,

4H), 7.48 (s, 2H), 7.44

(d, 7 = 8.0 Hz, IH), 7.38

151- 554.04 (m, IH), 6.42 (m, IH),

CC46

153 5.92 (br s, IH), 4.92 (m,

([M-H]-)

2H), 4.24 (m, IH), 3.12

(m, 2H)

8.06 (m, 2H), 7.61 (m,

4H), 7.48 (s, 2H), 7.44

(d, 7 = 8.0 Hz, IH), 7.38

478.09 3309, 1659,

CC47 (m, 2H), 6.42 (m, IH),

([M+H]⁺) 1115, 808

4.92 (s, 2H), 1.36 (m,

IH), 1.00 (m, 2H), 0.77

(m, 2H)

8.06 (m, 2H), 7.61 (m,

3H), 7.48 (s, 2H), 7.44

(d, 7 = 8.0 Hz, IH), 7.38

511.05 3309, 1659,

CC48 (m, 2H), 6.42 (m, IH),

([M+H]⁺) 1115, 808

4.92 (s, 2H), 1.36 (m,

IH), 1.00 (m, 2H), 0.77

(m, 2H)

8.06 (m, IH), 7.98 (m,

IH), 7.61 (m, 3H), 7.48

(s, 2H), 7.44 (d, 7 = 8.0

Hz, IH), 7.38 (m, 2H),

515.33

CC49 84-87 6.42 (m, IH), 4.92 (s,

([M+H]⁺). 2H), 4.6 (br s, IH), 4.24

(m, IH), 3.21 (m, 2H),

1.2 (t, 7 = 4.6 Hz, 3H)

9.81 (s, IH), 7.90 (s,

IH), 7.84 (s, 2H), 7.34

(d, 7 = 8.4 Hz, 2H), 6.65

(d, 7 = 15.6 Hz, IH),

138- 461.32 6.61 (m, IH), 6.57 (s,

CC50

140 IH), 6.48 (dd, 7 = 15.6, ([M-1H]-)

8.8 Hz, IH), 4.74 (m,

IH), 1.64 (m, IH), 0.75

(m, 4H); 7.56 (brs, IH), 7.4 (s,

3H), 7.3 (m, 3H), 7.05

(brs, IH), 6.8 (d, 7=6

149- 505.31

CC51 Hz, 2H), 6.57 (m, 2H),

150 ([M-H]-) 6.20 (m, 2H), 4.05 (m,

IH), 3.2 (q,7 = 10.4 Hz,

2H)

7.40 (s,2H), 7.18 (s,

IH), 7.08 (s, IH), 6.85

(m, IH), 6.45 (m, IH),

464.87 3309, 1659,

CC52 6.20 (m, IH), 5.55

([M-H]) 1115,808

(s,lH), 4.08 (m, IH),

1.30- 1.10 (m, 4H),

1.90 (m,lH)

7.40 (s,2H), 7.18 (s,

IH), 7.08 (s, IH), 6.85

506 (m, IH), 6.45 (m, IH), 3309, 1659,

CC53

([M+H]⁺) 6.20 (m, IH), 5.55 1115,808

(s,lH), 4.08 (m, IH),

3.21 (m, 2H)

7.28 (s, 2H), 7.25 (m,

2H),7.10 (d, 7=8.0 Hz,

2H), 6.89 (d,7 = 11.4

504 Hz, IH), 6.07 (br s, IH),

CC54

([M+H]⁺) 6.01 (m, 1H),4.51 (d, 7

= 5.8 Hz, 2H), 4.34 (m,

IH), 3.12 (q, 7 = 7.5 Hz,

2H)

8.56 (s, IH), 8.11 (s,

1H),7.68 (d, 7=8.4 Hz,

2H), 7.54 (d, 7=8.4 Hz,

398.05 2H),7.38 (t,7= 1.8 Hz,

DCl 93-97

«M+H]⁺) IH), 7.29 (s, 2H), 6.62

(d,7= 15.6 Hz, IH),

6.42 (dd,7= 15.6, 8.2

Hz, IH), 4.15 (m, IH)

8.59 (s, IH), 8.13 (s,

1H),7.69 (d,7=8.5 Hz,

2H),7.55 (d,7=8.5 Hz,

3121, 1524,

363.0746 2H), 7.41 - 7.29 (m,

DC2 1251, 1165,

(363.075) 4H), 6.64 (d,7= 15.7

1119 Hz, IH), 6.47 (dd, 7 =

15.9, 8.0 Hz, IH), 4.17

(m, IH) 8.56 (s, IH), 8.11 (s,

1H),7.65 (d, 7=8.4 Hz,

2H),7.52 (d, 7=8.3 Hz, 1521, 1246,

329.1144

DC3 2H), 7.40 (m, 5H), 6.61 1219, 1162,

(329.114)

(d,7= 15.8 Hz, IH), 1152, 1107 6.51 (dd,7= 15.9,7.7

Hz, IH), 4.18 (m, IH)

8.56 (s, IH), 8.10 (s,

1H),7.66 (d,7 = 2.0 Hz,

2H),7.52 (d,7=8.8 Hz,

2H), 7.38 (d, 7 = 2.4 Hz, 3147, 1528,

364.11

DC4 2H), 7.34 (d, 7=8.4 Hz, 1494, 1246,

«M+H]⁺)

2H), 6.61 (d,7= 16.0 1165, 1108 Hz, IH), 6.40 (dd, 7 =

16.0, 7.6 Hz, IH), 4.15

(m, IH)

8.54 (s, IH), 8.10 (s,

1H),7.62 (d,7=8.3 Hz,

2H),7.50 (d,7=8.4 Hz,

2H),7.25 (d,7=8.3 Hz, 3122, 3047,

344.25

DC5 2H),7.20 (d,7=8.0 Hz, 1523, 1252,

«M+H]⁺)

2H), 6.60 (d,7= 16.0 1160, 1107 Hz, IH), 6.51 (dd, 7 =

16.0, 8.0 Hz, IH), 4.15

(m, IH), 2.37 (s, 3H)

8.55 (s, IH), 8.10 (s,

1H),7.65 (d,7=8.8 Hz,

2H),7.52 (d,7=8.8 Hz,

2H),7.32 (d,7=8.8 Hz, 3124, 2936,

360.28

DC6 2H), 6.95 (d,7=8.8 Hz, 1522, 1249,

«M+H]⁺)

2H), 6.60 (d,7= 16.0 1160 Hz, IH), 6.56 (dd,7 =

16.0, 7.4 Hz, IH), 4.15

(m, IH), 3.82 (s, 3H)

8.55 (s, IH), 8.10 (s,

1H),7.62 (d,7=8.8 Hz,

2H),7.5 (d, 7 =8.4 Hz,

348 2H), 7.38 (m, 2H), 7.12 3141, 1512,

DC7

«M+H]⁺) (m, 2H), 6.61 (d,7 = 1246, 1118

16.0 Hz, IH), 6.40 (dd,

7= 16.0, 7.6 Hz, IH),

4.15 (m, IH) 8.57 (s, IH), 8.11 (s,

IH), 7.65 (d, J = 1.2 Hz,

2H),7.52 (d, 7=8.0 Hz,

3116, 1628,

366.13 2H), 6.95 (m, 2H), 6.82

DC8 1524, 1252,

([M+H]⁺) (m, IH), 6.65 (d,7 =

1168, 1118 16.0 Hz, IH), 6.50 (dd,

7 = 16.0, 8.0 Hz, IH),

4.15 (m, IH)

8.71 (s, IH), 8.20 (s,

1H),7.70 (d, 7=8.0 Hz,

2H),7.57 (d, 7=8.0 Hz,

348.11 2H),7.40 (m, IH), 7.19 3115, 1525,

DC9

«M+H]⁺) (m, 3H), 6.60 (d,7 = 1248, 1174

16.0 Hz, IH), 6.40 (dd,

7= 16.0, 8.4 Hz, IH),

4.15 (m, IH)

8.75 (s, IH), 8.20 (s,

IH), 7.72 (d, 7=8.4 Hz,

2H), 7.6 (d, 7 =8.4 Hz,

3114, 1526,

348.11 2H), 7.20 - 7.40 (m,

DC10 1259, 1238,

«M+H]⁺) 4H), 6.60 (d,7= 16.0

1193, 1114 Hz, IH), 6.40 (dd, 7 =

16.0, 8.0 Hz, IH,), 4.60

(m, IH)

8.55 (s, IH), 8.10 (s,

1H),7.65 (d,7=8.8 Hz,

2H), 7.52 (d, 7=8.4 Hz,

75.5- 358.14 2H), 7.01 (s, 3H), 6.60

DC11

78.5 ([M+H]⁺) (d,7= 16.0 Hz, IH),

6.51 (dd,7= 16.0,7.8

Hz, IH), 4.15 (m, IH),

2.34 (s, 6H)

8.58 (s, IH), 8.10 (s,

1H),7.68 (d,7=8.4 Hz,

2H), 7.53 (m, 4H), 7.2 3055, 2930,

398.05

DC12 (s, IH) 6.62 (d,7= 15.6 1523, 1250,

([M+H]⁺)

Hz, IH), 6.44 (dd, 7 = 1165 15.6, 8.0 Hz, IH), 4.15

(m, IH) 8.58 (s, IH), 8.10 (s,

IH), 7.62 (d, 7=8.4 Hz,

2H), 7.55 (m, 4H), 7.25 3108, 1523,

396.16

DC13 (m, IH), 6.64 (d,7 = 1249, 1166,

([Μ+ΗΓ)

16.0 Hz, IH), 6.40 (dd, 1127

7 = 16.0, 8.0 Hz, IH),

4.90 (m, IH)

8.58 (s, IH), 8.10 (s,

IH), 7.62 (d, 7=8.4 Hz,

2H), 7.55 (m, 4H), 7.25 3117,2925,

398.05

DC14 (m, IH), 6.67 (d,7 = 1526, 1246,

«M+H]⁺)

16.0 Hz, IH), 6.40 (dd, 1172, 1117 7 = 16.0, 8.0 Hz, IH),

5.00 (m, IH)

8.58 (s, IH), 8.10 (s,

1H),7.66 (d, 7=8.0 Hz,

2H), 7.52 (m, 3H), 7.40

(d, 7 = 8.0 Hz, IH), 7.30 3120, 1524,

397.95

DC15 (dd,7=8.4, 2.9 Hz, 1267, 1176,

«M+H]⁺)

IH), 6.64 (d,7= 16.0 1112 Hz, IH), 6.40 (dd, 7 =

16.0, 8.0 Hz, IH), 4.90

(m, IH)

8.61 (s, IH), 8.13 (s,

IH), 7.92 (s, IH), 7.86

(s,2H), 7.70 (d,7 = 7.0

466 Hz, 2H), 7.54 (d, 7 = 7.0

DC16

«M+H]⁺) Hz, 2H), 6.67 (d,7 =

16.0 Hz, IH), 6.46 (dd,

7= 16.0, 8.0 Hz, IH),

4.35 (m, IH)

8.58 (s, IH), 8.1 (s, IH),

7.68 (d, 7 =8.4 Hz, 2H),

7.54 (d, 7 =8.4 Hz, 2H), 3122, 3076,

430.06 7.51 (s, IH), 7.42 (s, 2929, 1523,

DC17

([M+H]⁺) IH), 6.68 (d,7= 16.0 1250, 1168,

Hz, IH), 6.35 (dd,7 = 1114 16.0, 8.0, Hz, IH), 4.98

(m, IH) 8.57 (s, IH), 8.11 (s,

1H),7.69 (d, 7=8.8 Hz,

2H), 7.54 (d, 7=8.4 Hz,

429.91

DC18 92-95 2H), 7.42 (s, 2H), 6.65

([Μ+ΗΓ)

(d,7= 16.0 Hz, IH),

6.40 (dd,7= 16.0, 8.0

Hz, IH), 4.10 (m, IH)

8.58 (s, IH), 8.12 (s,

1H),7.68 (d,7=8.0 Hz,

2H), 7.64 (s, IH), 7.59

430.321 (s, IH), 7.55 (m, 3H),

DC19 97-99

«M+H]⁺) 6.60 (d,7= 16.0 Hz,

IH), 6.40 (dd,7= 16.0,

8.0 Hz, IH), 4.22 (m,

IH)

8.58 (s, IH), 8.15 (s,

IH), 7.70 (d, 7=8.4 Hz,

2H),7.58 (d,7=8.4 Hz, 2937, 1524,

427.0463

2H), 7.36 (s, 2H), 6.62 1482, 1278,

DC20 (427.0466

(d,7= 16.0 Hz, IH), 1249, 1166,

) 6.43 (dd,7= 16.0, 8.0 1112

Hz, IH), 4.12 (m, IH),

3.88 (s, 3H)

8.42 (s, IH), 7.60 (d,7 =

8.0 Hz, 2H), 7.50 (d,7 =

8.0 Hz, 2H), 7.40 (s,

3108, 1572,

412.04 IH), 7.22 (s, 2H), 6.60

DC21 1531, 1242,

«M+H]⁺) (d,7= 16.0 Hz, IH),

1172, 1104 6.42 (dd,7= 16.0, 8.0

Hz, IH), 4.15 (m, IH),

2.5 (s, 3H)

8.62 (s, IH), 7.78 (d,7 =

8.0 Hz, 2H), 7.60 (d,7 =

8.0 Hz, 2H), 7.40 (s,

147- 441.01

DC22 IH), 7.30 (s, 2H), 6.67

149 ([M-H]-)

(d,7= 16.0 Hz, IH),

6.48 (dd, 7= 16.0, 8.0

Hz, IH), 4.15 (m, IH) 7.95 (s, IH), 7.35 (d,/ =

8.0 Hz, 2H), 7.46 (d,/ =

8.0 Hz, 2H), 7.39 (s,

412.05 IH), 7.29 (s, 2H), 6.67

DC23 1112, 799

([Μ+ΗΓ) (d,/ = 16.0 Hz, IH),

6.45 (dd,/ = 16.0, 8.0

Hz, IH), 4.12 (m, IH),

2.51 (s, 3H)

8.10 (s, IH), 7.52 (d,/ =

8.0 Hz, 2H), 7.42-7.38

(m, 3H), 7.28 (s, 2H),

133- 440.03

DC24 6.67 (d,/ = 16.0 Hz,

134 ([M+H]⁺)

IH), 6.45 (dd, 7=16.0,

8.0 Hz, IH), 4.16 (m,

IH), 2.79 (s, 3H)

7.97 (s, IH), 7.59 (d,/ =

8.0 Hz, 2H), 7.53 (d,/ =

8.0 Hz, 2H), 7.38 (m,

442.02 IH), 7.29 (s, 2H), 6.65 1167, 1114,

DC25

([M-H]-) (d,/ = 16.0 Hz, IH), 800

6.42 (dd,/ = 16.0, 8.0

Hz, IH), 4.17 (m, IH),

2.74 (s, 3H)

8.12 (s, IH), 7.49 (d,/ =

8.0 Hz, 2H), 7.40-7.37

(m 3H), 7.28 (s, 2H),

1689, 1253,

464.03 6.66 (d,/ = 16.0 Hz,

DC26 1166, 1114,

([M-H]) IH), 6.44 (dd,/ = 16.0,

979, 964 8.0 Hz, IH), 4.14 (m,

IH), 3.22 (m, IH), 1.09

-1.16(m, 4H)

8.19 (s, IH), 7.64 (d,/ =

7.2 Hz, 2H), 7.55 (d, 7.2

Hz, 2H), 7.39 (s, IH),

1571, 1331,

473.94 7.30 (s,2H), 6.62 (d,/ =

DC27 1170, 1113,

([M-H]) 16.0 Hz, IH), 6.42 (dd,

764 7=8.0, 16.0 Hz, IH),

4.18 (m, IH), 3.58 (s,

3H) 8.79 (s, IH), 8.18 (s,

IH), 7.80 (m, 3H), 7.52

(m, 2H), 7.24 (m, IH), 3126, 2233,

421.22

DC28 6.63 (d, / = 16.0 Hz, 1516, 1250,

([Μ+ΗΓ)

IH), 6.54 (d, / = 16.0, 1165, 1109 7.6 Hz, IH), 4.19 ( m,

IH)

8.80 (s, IH), 8.2 (s, IH),

7.75 - 7.82 (m, 3H),

7.41 (t, J = 2 Hz, IH),

421.22 3005, 1716,

DC29 7.26 (m, 2H), 6.65 (d, J

«M+H]⁺) 1363, 1223

= 16.0 Hz, IH), 6.52

(dd, / = 16.0, 7.6 Hz,

lH), 4.16 (m, IH)

8.81 (s, IH), 8.20 (s,

IH), 7.94 (s, IH), 7.85

(m, 3H), 7.79 (m, 2H), 2964, 2234,

489.17

DC30 6.70 (d, / = 16.0 Hz, 1289, 1166,

«M+H]⁺)

IH), 6.58 (dd, / = 16.0, 1136 8.0 Hz, IH), 4.35 (m,

IH)

8.80 (s, IH), 8.20 (s,

IH), 7.82 (m, 3H), 7.4

117- 455.27 (s, 2H), 6.62 (d, 7 = 16.0

DC31

118 «M+H]⁺) Hz, IH), 6.52 (dd, / =

16.0, 8.0 Hz, IH), 4.18

(m, IH)

8.82 (s, IH), 8.22 (s,

IH), 7.82-7.78 (m, 3H),

388.0705 3126, 2234,

7.38-7.30 (m, 3H), 6.62

DC32 (388.0703 1520, 1280,

(d, / = 16.1 Hz, IH),

) 1164, 1112

6.56 (dd, / = 16.1, 6.8

Hz, IH), 4.18 (m, IH)

8.80 (s, IH), 8.20 (s,

IH), 7.82-7.80 (m, 3H), 3122, 3086,

455.22 7.70-7.50 (m, 3H), 6.65 2234, 1517,

DC33

([M-H]-) (d, 7 = 16.9 Hz, IH), 1327, 1168,

6.54 (dd, / = 16.9, 6.8 1113 Hz, IH), 4.25 (m, IH) 8.85 (s, IH), 8.23 (brs,

IH), 7.83-7.78 (m, 3H), 3122, 2934,

452.0412 7.33 (s,2H), 6.69 (d,/ = 2231, 1516,

DC34 (452.0419 14.9 Hz, IH), 6.50 (dd, 1480, 1248,

) /= 14.9, 7.2 Hz, IH), 1211, 1165,

4.15 (m, IH), 3.90 (s, 1111 3H)

8.60 (s, IH), 8.20 (s,

IH), 7.82 (m, 3H), 7.28

2233, 1518,

439.01 (m, 2H), 6.65 (d,/ =

DC35 1250, 1169,

([M-H]-) 16.0 Hz, IH), 6.48 (dd,

1035,817 /= 16.0, 8.0 Hz, IH),

4.20 (m, IH)

8.70 (s, IH), 7.80 (m,

3H), 7.40 (s, IH), 7.28 2927, 2233,

437.25 (s,2H), 6.63 (d,/= 16.0 1572, 1531,

DC36

([M+H]⁺) Hz, IH), 6.50 (dd,/ = 1248, 1166,

16.0, 8.0 Hz, IH), 4.18 1112 (m, IH), 2.50 (s, IH)

8.86 (s, IH), 7.89 (m,

3H), 7.40 (s, IH), 7.30

109- 466.10 (s,2H), 6.68 (d,/= 16.0

DC37

111 ([M-H]^") Hz, IH), 6.57 (dd, / =

16.0, 8.0 Hz, IH), 4.18

(m, IH)

8.58 (s, IH), 7.75 (m,

3H), 7.40 (s, IH), 7.28

436.11 (s,2H), 6.61 (d,/= 16.0

DC38 96-98

([M-H]^") Hz, IH), 6.42 (dd, / =

16.0, 8.2 Hz, IH), 4.40

(brs, 2H), 4.15 (m, IH)

8.65 (s, IH), 8.18 (brs,

IH), 7.80-7.70 (m, 3H),

7.40 (s, IH), 7.27 (s,

3352, 2237,

224- 480.30 2H), 7.36 (m, IH), 7.28

DC39 1707, 1163,

226 «M+H]⁺) (m, 2H), 6.60 (d,/ =

841 16.8 Hz, IH), 6.47 (m,

lH),4.16(m, IH), 2.40

(br s, 3H)

8.86 (s, IH), 7.88 (m,

3H), 7.44 (s, 2H), 6.67

436.11

DC40 70-73 (d,/= 16.0 Hz, IH),

([M-2H])

6.56(dd,/= 16.07.6

Hz, IH), 4.19 (m, IH) (DMSO- ) 8.72 (s,

IH), 8.26 (s, IH), 8.01

(d, 7=8.4 Hz, IH), 7.91

(s,2H), 7.77 (d, 7=8.4

469.95

DC41 72-75 Hz, IH), 6.42 (dd, 7 =

([M-H]-)

15.6, 9.2 Hz, IH), 6.83

(d,7= 15.6 Hz, IH),

5.87 (s, 2H), 4.89 (m,

IH)

8.78 (s, 2H), 7.83 (s,

IH), 7.80 (m, 2H), 7.42

(s,2H), 6.65 (d,7= 16.4

104- 609.98 Hz, IH), 6.51 (dd, 7 = 2234, 1714,

DC42

107 ([M+H]⁺) 16.4, 7.8 Hz, IH), 4.17 1114, 807

(m, IH), 42.16 (m, 2H),

1.25 (m, 4H), 1.00 (m,

4H),

(DMSO- ) 10.94 (br s,

IH), 8.36 (s, IH), 8.08

(m, 7 =8.4 Hz, IH),

7.91 (s,2H), 7.84 (d,7 = 3233, 2233,

109- 540.04

DC43 8.4 Hz, IH), 7.13 (dd, 7 1699, 1114,

112 ([M+H]⁺)

= 15.6, 9.2 Hz, IH), 807 6.87 (d,7= 15.6 Hz,

IH), 4.92 (m, IH), 1.99

(br s, IH), 0.82 (s, 4H)

8.33 (s, IH), 8.23 (s,

IH), 7.66 (s, IH), 7.60

(s, IH), 7.41 (m, IH),

435.26 7.28 (m, 2H), 6.62 (d, 7 2236,1510,

DC44

[M-H]^" = 16.0 Hz, IH), 6.51 1114, 801

(dd,7= 16.0, 7.8 Hz,

lH),4.16(m, IH), 2.20

(s, 3H)

8.36 (s, IH), 8.23 (s,

IH), 7.66 (s, IH), 7.60

468.87 (s, IH), 7.41 (s, 2H),

DC45 75-78 6.62 (d, 7= 16.4 Hz,

[M-H]^" IH), 6.51 (dd,7= 16.4,

7.6 Hz, IH), 4.16 (m,

IH), 2.20 (s, 3H) ¹³C NMR (δ)³

155.63, 153.27,

8.83 (s, IH), 8.21 (s, 153.12, 1H),7.83 (d, 7=8.5 Hz, 143.01, 1H),7.61 (d,/ = 1.9 Hz, 137.89,

136.25,

411.4 IH), 7.52 (dd, J = 8.4,

DC46 I.9 Hz, IH), 7.28 (d,/ = 134.03,

([M]⁺) 3.8 Hz, 2H), 6.93 (d,/ = 133.88,

II.5 Hz, IH), 6.26- 132.23, 6.20 (m, IH), 4.22 (m, 131.23, IH) 131.18,

129.20, 126.17, 125.04, 124.99

8.51 (s, IH), 8.14 (s,

IH), 7.75 (s, IH), 7.5

(m, 2H), 7.4 (s, IH),

139- 474.16

DC47 7.30 (m, 2H), 6.60 (d, J

141 ([M-H])

= 16.0 Hz, IH), 6.50

(dd,/ = 16.0, 8.0 Hz,

1H),4.15 (m, IH)

8.69 (s, IH), 8.14 (s,

1H),7.96 (d, 7 = 4.8 Hz,

IH), 7.39-7.27 (m, 5H),

124- 414.05

DC48 6.95 (d,/= 16.0 Hz,

126 [M-H]^" IH), 6.51 (dd,/= 16.0,

7.6 Hz, IH), 4.13 (m,

IH)

8.57 (s, IH), 8.14 (s,

IH), 7.60 (m, 2H), 7.44

463.96 (m, 3H), 6.95 (d,/ =

DC49 81-83

[M-H]^" 16.0 Hz, IH), 6.51 (dd,

/= 16.0, 7.6 Hz, IH),

4.13 (m, IH)

8.56 (s, IH), 8.13 (s,

1H),7.59 (d,/= 1.2 Hz,

2H), 7.44 (m, 2H), 7.28

140- 430.07

DC50 (m, 2H), 6.61 (d,/ = 1110, 803

143 [M-H]) 16.0 Hz, IH), 6.47 (dd,

/= 16.0, 8.0 Hz, IH),

4.15 (m, IH) 8.32 (s, IH), 8.15 (s,

IH), 7.82 (s, IH), 7.73

(d, 7=8.4 Hz, IH), 7.53

(d, 7=8.4 Hz, IH), 7.41

118- 464.22

DC51 (s, IH), 7.29 (s, 2H),

121 ([M-H]-)

6.70 (d,7= 15.6 Hz,

IH), 6.50 (dd,7= 15.6,

8.0 Hz, IH), 4.20 (m,

IH)

9.99 (s, IH), 8.42 (s,

IH), 8.12 (s, IH), 8.01

3123, 3079, (s, IH), 7.68 (m, IH),

2925, 1692,

7.44 (m, IH), 7.33 (m,

DC52 1571, 1512,

IH), 7.22 (s, 2H), 6.62

1253, 1164, (d, 7 =16.7 Hz, IH),

1111

6.45 (dd,7= 16.7, 9.3

Hz, IH), 4.10 (m, IH)

8.30 (m, IH), 8.00 (br s,

IH), 7.75 (m, 1H),7.68

(m, IH), 7.55 (m, IH),

7.36 (m, IH), 7.28 (m, 3250, 3043,

DC53

2H), 6.70 (m, IH), 6.58 1683, 1116 (br s, IH), 6.33 (m, IH),

5.88 (m, 2H),4.10(m,

IH)

8.40 (s, IH), 8.13 (s,

IH), 8.02 (s, IH), 7.76

(d, 7 = 8.4 Hz, IH), 7.59

(d, 7 = 8.0 Hz, IH), 7.4

441.07

DC54 56-58 (s, IH), 7.29 (m, 2H),

([M-H])

6.69 (d,7= 15.6 Hz,

IH), 6.57 (dd,7= 15.6,

7.8 Hz, IH), 4.15 (m,

IH)

8.37 (s, IH), 8.18 (s,

IH), 7.39 (s, IH), 7.30

(m, 2H), 7.19 (d, 7= 8.0

412.97 Hz, IH), 6.90 (m, 2H),

DC55

([M+H]⁺) 6.55 (d,7= 15.6 Hz,

IH), 6.38 (dd,7= 15.6,

8.2 Hz, IH), 4.20 (m,

IH), 2.50 (br s, 2H) 9.59 (brs, IH), 8.55 (s,

IH), 8.47 (s, 2H), 8.23

(s, IH), 7.30 (m, 4H),

175- 453

DC56 6.62 (d,7 = 16.0 Hz,

177 ([M-H]-)

IH), 6.40 (dd,7 = 16.0,

8.0 Hz, IH), 4.15 (m,

IH), 2.20 (s, 3H)

8.33 (s, IH), 8.16 (s,

IH), 7.38 (s, IH), 7.29

(s,2H), 7.15 (d, 7 = 7.6

Hz, IH), 6.80 (d, 7 = 7.6 3342,3112,

426.0627

Hz, IH), 6.74 (m, IH), 2931, 1606,

DC57 (426.0626

6.60 (d,7= 15.6 Hz, 1583, 1574,

) IH), 6.35 (dd,7=15.6, 1528, 1153

8.4 Hz, IH), 5.40 (brs,

lH),4.15(m, IH), 2.90

(s, 3H)

(DMSO- ) 8.76 (s,

IH), 8.16 (s, 1H),7.90

(br s, IH), 7.83 (s, IH),

7.70 (d, 7 = 7.9 Hz, IH), 3403, 3304,

440.0424

7.71-7.67 (m, 3H), 7.58 3178, 1674,

DC58 94-97 (440.0419

(d, 7 = 7.9 Hz, IH), 7.52 1571, 1169,

) (brs, IH), 7.00 (dd, 7 = 1108

15.8, 8.7 Hz, IH), 6.85

(d, 7= 15.8 Hz, IH),

4.85 (m, IH)

(DMSO- ) 9.00 (s,

IH), 8.63 (s, IH), 8.17

(s, IH), 7.70-7.59 (m,

DC59 87-90 5H),7.00 (dd,7= 16.2,

9.7 Hz, IH), 6.85 (d,7 =

16.2 Hz, IH), 5.90 (br s

2H), 4.83 (m, IH)

8.32 (s, IH), 8.10 (s,

IH), 7.97 (s, IH), 7.65

(d, 7 = 8.1 Hz, IH), 7.47

(d, 7 = 8.1 Hz, IH), 7.40

469.0577 2987, 1725,

(m, IH), 7.28 (s, 2H),

DC60 (469.0572 1518, 1275,

6.62 (d,7= 16.5 Hz,

) 1166, 1113

IH), 6.49 (dd,7= 16.5,

7.7 Hz, IH), 4.23-4.04

(m, 3H), 1.15 (t, 7= 8.0

Hz, 3H) (DMSO- ) 9.90 (s,

IH), 8.17 (s, IH), 8.15

(m, IH), 7.90 (m, IH),

7.71 (m, 2H), 7.67 (m,

442.15

130- IH), 7.62 (d, 7 = 7.3 Hz,

DC61 ([Μ+ΗΓ)

132 1H),7.03 (dd,7 = 16.5,

8.3 Hz, IH), 6.62 (d,7 =

16.5 Hz, IH), 4.87 (m,

IH)

8.27 (s, IH), 8.23 (s,

IH), 7.40 (m, 3H), 7.30

(m, 3H), 6.64 (d,7 = 1513, 1252,

412.10

DC62 16.0 Hz, IH), 6.45 (dd, 1166, 1112,

«M+H]⁺)

7 = 16.0, 8.0 Hz, IH), 801 4.19 (m, 1H),2.21 (s,

3H)

8.26 (s, IH), 8.12 (s,

1H),7.42 (s, 2H),7.18-

2928,

446.01 7.28 (m, 3H), 6.62 (d, 7

2525,1249,

DC63 = 15.6 Hz, IH), 6.39

«M+H]⁺) 1169, 1114,

(dd,7 = 15.6, 9.4 Hz,

809 1H),4.10 (m, IH), 2.25

(s, 3H)

8.84 (d, 7=5.8 Hz, 2H),

8.33 (s, IH), 8.20 (s,

IH), 7.75 (m, IH), 7.60

(d, 7 = 28.6 Hz, IH),

475.03 7.58-7.48 (m, 3H), 7.42 1683, 1167,

DC64

([M+H]⁺) (m, IH), 7.28 (s, 2H), 650, 479

6.71 (d,7= 16.9 Hz,

IH), 6.39 (dd,7= 16.9,

8.2 Hz, IH), 4.15 (m,

IH)

8.55 (s, IH), 8.12 (s,

IH), 7.55 (m, 3H), 7.39

(m, IH), 7.30 (d,7= 1.6

412.05 Hz, IH), 6.85 (d,7 =

DC65 722, 111

([M+H]⁺) 16.0 Hz, IH), 6.41 (dd,

7= 16.0, 8.0 Hz, IH),

4.17 (m, 1H),2.40 (s,

3H) 8.59 (s, 1H), 8.14 (s,

1H), 7.94 (s, 1H), 7.70

(d, 7=8.0 Hz, 1H), 7.61

468.26 (d, 7 =8.0 Hz, 1H), 7.43

DC66 60-61

([M+H]⁺) (s,2H), 7.23 (d,7 = 16.0

Hz, 1H), 6.41 (dd, 7 =

16.0, 8.0 Hz, 1H), 4.20

(m, 1H)

8.59 (s, 1H), 8.12 (s,

1H), 7.78 (br s, 1H),

7.71 (m, 1H), 7.62 (m,

133- 432.30 1H), 7.39 (s, 1H), 7.32

DC67 800, 114

134 ([M+H]⁺) (s,2H), 7.03 (d,7 = 16.0

Hz, 1H), 6.43 (dd, 7 =

16.0, 8.0 Hz, 1H), 0.21

(m, 1H)

8.71 (s, 1H), 8.18 (s,

1H), 7.71 (d, 7=8.0 Hz,

2H),7.55 (d, 7=8.0 Hz,

412.03

DC68 2H), 7.37 (s, 1H), 7.28

«M+H]⁺)

(m, 2H), 6.08 (d,7 =

16.0 Hz, 1H), 4.26 (m,

1H), 2.05 (s, 3H)

8.56 (s, 1H), 8.11 (s,

1H),7.70 (d, .7=8.5 Hz,

2H),7.56 (d, 7=8.5 Hz,

162- 414.03

DC69 2H), 7.54 (m, 2H), 7.40

168 ([M+H]⁺)

(m, 1H), 6.91 (d,7 =

16.5 Hz, 1H), 6.66 (d, 7

= 16.5 Hz, 1H)

8.58 (s, 1H), 8.13 (s,

1H), 7.73 (d, 7=8.7 Hz,

2H),7.60 (d,7=8.7 Hz,

99- 428.05 2H), 7.46 (m, 2H), 7.42

DC70

103 ([M+H]⁺) (m, 1H), 6.85 (d,7 =

16.2 Hz, 1H), 6.40 (d, 7

= 16.2 Hz, 1H), 3.42 (s,

3H) ¾ NMR spectral data were acquired using a 400 MHz instrument in CDC1₃ except where noted. HRMS data are noted observed value (theoretical value). Table 2A: Analytical Data for Compounds in Table 1A.

¾ NMR spectral data were acquired using a 400 MHz instrument in CDC1₃ except where noted. HRMS data are noted observed value (theoretical value).

Table 2B: Analytical Data for FA Compounds in Table IB.

(300 MHz, DMSO-d₆) δ

10.70 (s, 1H), 7.89 (s,

2H), 7.54 (s, 1H), 7.48 - 7.40 (m, 2H), 6.93 (dd, 7

= 15.6, 9.0 Hz, 1H),

505.0 3438, 1671,

FA4 6.77 (d, 7 = 15.6 Hz,

([M-H]-) 1110, 807

1H), 4.87 - 4.81 (m,

1H), 3.07 (s, 3H), 2.39

(s, 3H), 1.29 - 1.26 (m,

2H), 1.01 (t, J = 1.2 Hz,

3H)

(300 MHz, DMSO-d₆) δ

10.70 (s, 1H), 7.89 (s,

2H), 7.54 (s, 1H), 7.50

(s, 2H), 6.93 (dd, 7 =

15.6, 9.0 Hz, 1H), 6.77

516.8 3451, 1653,

FA5 (d, 7 = 15.6 Hz, 1H),

([M-H]^") 1114, 808

4.87 - 4.81 (m, 1H),

3.09 (s, 3H), 2.39 (s,

3H), 2.02 - 1.98 (m,

1H), 1.33 - 1.23 (m,

2H), 0.75 - 0.73 (m, 2H)

(300 MHz, DMSO-d₆) δ

10.70 (s, 1H), 7.89 (s,

2H), 7.55 - 7.44 (m,

3H), 6.94 (dd, 7 = 15.9,

573.0 9.0 Hz, 1H), 6.78 (d, 7 = 3436, 1685,

FA6

([M-H] ) 15.9 Hz, 1H), 4.84 - 1114, 750

4.82 (m, 1H), 3.11 (s,

3H), 2.51 - 2.49 (m,

2H), 2.41 (s, 3H), 1.29 - 1.23 (m, 2H)

7.68 - 7.67 (m, 1H),

7.60 (dd, 7 = 8.0, 1.6

Hz, 1H), 7.41 (s, 3H), ¹⁹F NMR 6.68 (s, 1H), 6.66 - 6.58 (376 MHz,

631 (m, 1H), 6.44 (dd, 7 = CDC1₃) δ

FA7 52-65

«M+H]⁺) 15.9, 7.8 Hz, 1H), 6.38 -59.04,

(t, 7 = 5.8 Hz, 1H), 4.12 -63.11, (q, 7 = 7.2 Hz, 1H), 3.66 -68.58 - 3.52 (m, 4H), 3.07 (q,

7 = 10.5 Hz, 2H)

7.67 (d,/ = 1.6 Hz, 1H),

7.60 (d, 7=8.1 Hz, 1H),

7.51-7.42 (m, 1H),

7.41 (s, 2H),7.19(s,

^1VF NMR

1H), 6.62 (d,/ = 15.9

(376 MHz,

659 Hz, 1H), 6.43 (dd, / =

FA16 CDC1₃)5 - «M+H]⁺) 15.9, 7.8 Hz, 1H), 5.96

58.77, -63.07, (s, 1H),4.13 (p, J = 8.5

-68.59 Hz, 1H), 3.61 (d, J = 6.0

Hz, 2H), 3.10 (q, J =

10.6 Hz, 2H), 1.43 (s,

6H) H NMR spectral data were acquired using a 400 MHz instrument in CDC1₃ except where noted. HRMS data are noted observed value (theoretical value). Table 3: Assays Results

AC15 A A B

AC16 A A C

AC17 A A B

AC18 A A B

AC19 D D B

AC20 A A C

AC21 D D C

AC22 A A D

AC23 A A B

AC24 A A D

AC25 A A D

AC26 A A B

AC27 A A B

AC28 A A B

AC29 A A B

AC30 A A B

AC31 A A B

AC32 A A B

AC33 A A B

AC34 A A B

AC35 A A C

AC36 A A B

AC37 A A B

AC38 A A C

AC39 A A C

AC40 A A D AC41 A D D

AC42 A D D

AC43 A A B

AC44 A A B

AC45 A A D

AC46 A A D

AC47 D D B

AC48 A A B

AC49 A A B

AC50 A D B

AC51 A A B

AC52 A A B

AC53 A A B

AC54 A A B

AC57 A A B

AC58 A A B

AC59 A A B

AC60 A A B

AC61 A A B

AC62 A A D

AC63 A A B

AC64 A A B

AC65 A A B

AC66 A A B

AC67 A A B

AC68 A A D AC69 A A A

AC70 D D B

AC71 A A B

AC72 A A B

AC75 A A B

AC76 A A D

AC77 A A B

AC78 A A A

AC79 A A A

AC80 A A B

AC81 A D D

AC82 A A B

AC83 A A B

AC84 A A D

AC85 A A B

AC86 A A D

AC87 A A B

AC89 A A B

AC90 A A C

AC91 A A C

AC92 A A C

AC93 A D C

AC94 D B B

AC95 A A C

AC96 D D C

AC97 D D C AC98 A A C

AC99 A A C

AClOO C C C

AC101 D D C

AC102 D A C

AC103 A A D

AC104 A A B

AC105 A A D

AC106 A A B

AC107 B A D

AC108 B D D

AC109 D D C

AC110 A A C

AC111 A A C

AC112 A A C

AC113 B A D

AC114 A B D

AC115 A A D

AC116 C C C

AC117 A D B

AC118 A D D

BC1 A A D

BC2 A A D

BC3 A A D

BC4 A A B

BC5 A A B BC6 A A D

BC7 A A D

BC8 A A B

BC9 A A D

BC10 A A B

BC11 C C C

BC12 C C C

BC13 A A D

BC14 A D D

CC1 D D D

CC2 A A B

CC3 A A D

CC4 A B B

CC5 A A B

CC6 A A B

CC7 A A B

CC8 A A D

CC9 A A B

CCIO A A B

CC11 A A B

CC12 D D B

CC13 A A B

CC14 A D D

CC15 A A B

CC16 A A B

CC17 A A B CC18 A A B

CC19 A A B

CC20 A A D

CC21 A A D

CC22 A A B

CC23 A A B

CC24 A A D

CC25 A A B

CC26 A D B

CC27 A A D

CC28 A A D

CC29 A A B

CC30 A A D

CC31 B D C

CC32 A A B

CC33 A A B

CC34 A A B

CC35 D D D

CC36 A A D

CC37 A A D

CC38 A A D

CC39 D D B

CC40 D A D

CC41 D D B

CC42 D D D

CC43 A B B CC44 A A B

CC45 A A D

CC46 D A C

CC47 D D C

CC48 D D C

CC49 D D D

CC50 A A D

CC51 A A D

CC52 A D D

CC53 D D B

CC54 A A C

DC1 A A D

DC2 D D C

DC3 B D C

DC4 A D C

DC5 D D C

DC6 D D C

DC7 A D C

DC8 A D C

DC9 D D C

DCIO D D C

DC11 A D C

DC12 A A B

DC13 A A C

DC14 D D C

DC15 D D C DC16 A A C

DC17 A A C

DC18 A A C

DC19 A A C

DC20 A D C

DC21 D D C

DC22 D D C

DC23 D A C

DC24 D D C

DC25 D D C

DC26 D D C

DC27 D D C

DC28 A A B

DC29 A A C

DC30 A A C

DC31 A A B

DC32 D D C

DC33 A A C

DC34 A A B

DC35 A A B

DC36 D D C

DC37 A A C

DC38 A A C

DC39 A A C

DC40 A A C

DC41 A A C DC42 A A C

DC43 A A C

DC44 A A C

DC45 A A C

DC46 A A C

DC47 A A C

DC48 A A C

DC49 A A C

DC50 A A C

DC51 A A C

DC52 D D C

DC53 D A C

DC54 D D C

DC55 D D C

DC56 D D C

DC57 A A C

DC58 D D C

DC59 D D C

DC60 A A C

DC61 D D C

DC62 A A C

DC63 A A C

DC64 D D C

DC65 D A C

DC66 A A C

DC67 A A C DC68 A A C

DC69 D D C

DC70 A A C

Table 3A: Assays Results

Table 3B: Assays Results

Claims

WE CLAIM

Formula One

wherein:

(a) Rl is selected from

(1) H, F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), S(0)(C C₈)alkyl, S(0)(halo(Ci-C₈)alkyl), S(0)₂(C C₈)alkyl, S(0)₂(halo(C C₈)alkyl), N(R14)(R15),

(2) substituted (Ci-C₈)alkyl, wherein said substituted (Ci-C₈)alkyl has one or more substituents selected from CN and N0₂,

(3) substituted halo(Ci-C₈)alkyl, wherein said substituted halo(d- C₈)alkyl, has one or more substituents selected from CN and N0₂,

(4) substituted (Ci-C₈)alkoxy, wherein said substituted (Ci-C₈)alkoxy has one or more substituents selected from CN and N0₂, and

(5) substituted halo(Ci-C₈)alkoxy, wherein said substituted halo(C

C₈)alkoxy has one or more substituents selected from CN and N0₂;

(b) R2 is selected from

(1) H, F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), S(0)(C C₈)alkyl, S(0)(halo(Ci-C₈)alkyl), S(0)₂(C C₈)alkyl, S(0)₂(halo(C C₈)alkyl), N(R14)(R15),

(2) substituted (Ci-C₈)alkyl, wherein said substituted (Ci-C₈)alkyl has one or more substituents selected from CN and N0₂,

(3) substituted halo(Ci-C₈)alkyl, wherein said substituted halo(d- C₈)alkyl, has one or more substituents selected from CN and N0₂,

(4) substituted (Ci-C₈)alkoxy, wherein said substituted (Ci-C₈)alkoxy has one or more substituents selected from CN and N0₂, and (5) substituted halo(Ci-C₈)alkoxy, wherein said substituted halo(Cr C₈)alkoxy has one or more substituents selected from CN and N0₂;

(c) R3 is selected from

(1) H, F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), S(0)(C C₈)alkyl,

S(0)(halo(Ci-C₈)alkyl), S(0)₂(C C₈)alkyl, S(0)₂(halo(C C₈)alkyl), N(R14)(R15),

(2) substituted (Ci-C₈)alkyl, wherein said substituted (C C₈)alkyl has one or more substituents selected from CN and N0₂,

(3) substituted halo(Ci-C₈)alkyl, wherein said substituted halo(d- C₈)alkyl, has one or more substituents selected from CN and N0₂,

(4) substituted (Ci-C₈)alkoxy, wherein said substituted (Ci-C₈)alkoxy has one or more substituents selected from CN and N0₂, and

(5) substituted halo(Ci-C₈)alkoxy, wherein said substituted halo(Ci- C₈)alkoxy has one or more substituents selected from CN and N0₂;

(d) R4 is selected from

(1) H, F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), S(0)(C C₈)alkyl, S(0)(halo(Ci-C₈)alkyl), S(0)₂(C C₈)alkyl, S(0)₂(halo(C C₈)alkyl), N(R14)(R15),

(2) substituted (Ci-C₈)alkyl, wherein said substituted (Ci-C₈)alkyl has one or more substituents selected from CN and N0₂,

(3) substituted halo(Ci-C₈)alkyl, wherein said substituted halo(d- C₈)alkyl, has one or more substituents selected from CN and N0₂,

(4) substituted (Ci-C₈)alkoxy, wherein said substituted (Ci-C₈)alkoxy has one or more substituents selected from CN and N0₂, and

(5) substituted halo(Ci-C₈)alkoxy, wherein said substituted halo(C

C₈)alkoxy has one or more substituents selected from CN and N0₂;

(e) R5 is selected from

(1) H, F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), S(0)(C C₈)alkyl, S(0)(halo(Ci-C₈)alkyl), S(0)₂(C C₈)alkyl, S(0)₂(halo(C C₈)alkyl), N(R14)(R15),

(2) substituted (Ci-C₈)alkyl, wherein said substituted (Ci-C₈)alkyl has one or more substituents selected from CN and N0₂,

(3) substituted halo(Ci-C₈)alkyl, wherein said substituted halo(d- C₈)alkyl, has one or more substituents selected from CN and N0₂, (4) substituted (Ci-Cs)alkoxy, wherein said substituted (Ci-C₈)alkoxy has one or more substituents selected from CN and N0₂, and

(5) substituted halo(Ci-Cs)alkoxy, wherein said substituted halo(d- C₈)alkoxy has one or more substituents selected from CN and N0₂;

(f) R6 is a (C C₈)haloalkyl;

(g) R7 is selected from H, F, CI, Br, I, OH, (C C₈)alkoxy, and halo(C

C₈)alkoxy;

(h) R8 is selected from H, (C C₈)alkyl, halo(C C₈)alkyl, OR14, and

N(R14)(R15);

(i) R9 is selected from H, F, CI, Br, I, (C C₈)alkyl, halo(C C₈)alkyl, (C

C₈)alkoxy, halo(C C₈)alkoxy, OR14, and N(R14)(R15);

(j) RIO is selected from

(1) H, F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C

C₈)alkoxy, halo(C C₈)alkoxy, cyclo(C₃-C₆)alkyl, S(C C₈)alkyl, S(halo(C C₈)alkyl), S(0)(Ci-C₈)alkyl, S(0)(halo(C C₈)alkyl), S(0)₂(C C₈)alkyl, S(0)₂(halo(C C₈)alkyl), NR14R15, C(=0)H, C(=0)N(R14)(R15), CN(R14)(R15)(=NOH), (C=0)0(C C₈)alkyl, (C=0)OH, heterocyclyl, (C₂-C₈)alkenyl, halo(C₂-C₈)alkenyl, (C₂-C₈)alkynyl,

(2) substituted (Ci-C₈)alkyl, wherein said substituted (Ci-C₈)alkyl has one or more substituents selected from OH, (Ci-C₈)alkoxy, S(Ci-C₈)alkyl, S(0)(Ci-C₈)alkyl, S(0)₂(Ci-C₈)alkyl, NR14R15, and

(3) substituted halo(Ci-C₈)alkyl, wherein said substituted halo(d- C₈)alkyl, has one or more substituents selected from (C]-C₈)alkoxy, S(C]-C₈)alkyl, S(0)(Cr C₈)alkyl, S(0)₂(C C₈)alkyl, and N(R14)(R15);

(k) Rll is C(=X5)N(H)((Co-C₈)alkyl)N(Rlla)(C(=X5)(Rl lb))

wherein each X5 is independently selected from O or S, and

wherein each Rlla is independently selected from H, (Ci-C₈)alkyl, substituted (Ci-C₈)alkyl, halo(C C₈)alkyl, substituted halo(C C₈)alkyl, cyclo(C₃-C₈)alkyl, and substituted cyclo(C3-C₈)alkyl,

wherein each said substituted (Ci-C₈)alkyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, OC(=0)H, OH, S(Ci-C₈)alkyl, S(0)(C C₈)alkyl,

S(0)₂(Ci-C₈)alkyl, OS(0)₂aryl, N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, wherein each said substituted aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (Cr C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), N((Ci-C₈)alkyl)2 (wherein each (Ci-C₈)alkyl is independently selected), and oxo, wherein each said substituted heterocyclyl has one or more substituents selected from F, CI, Br, I, CN, NO2, (Ci-C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), C(=0)(C C₈)alkyl, C(=0)(C₃-C₆)cycloalkyl, S(=0)₂(C C₈)alkyl, NR14R15, and oxo, wherein each said substituted-aryl has one or more substituents selected from F, CI, Br, I, CN, NO2, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C

C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo,

wherein said substituted halo(Ci-C₈)alkyl, has one or more substituents selected from CN and NO2,

wherein said substituted cyclo(C3-C₈)alkyl, has one or more substituents selected from CN and NO2

wherein each Rl lb is independently selected from (Ci-C₈)alkyl, substituted (Cr C₈)alkyl, halo(Ci-C₈)alkyl, substituted halo(Ci-C₈)alkyl, cyclo(C3-C₈)alkyl, substituted cyclo(C₃-C₈)alkyl, (C₂-C₈)alkenyl, and (C₂-C₈)alkynyl,

wherein each said substituted (Ci-C₈)alkyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, OC(=0)H, OH, S(Ci-C₈)alkyl, S(0)(C C₈)alkyl, S(0)₂(Ci-C₈)alkyl, OS(0)₂aryl, N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, wherein each said substituted aryl has one or more substituents selected from F, CI, Br, I, CN, NO2, (Q- C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), N((Ci-C₈)alkyl)2 (wherein each (Ci-C₈)alkyl is independently selected), and oxo, wherein each said substituted heterocyclyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C

C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), C(=0)(C C₈)alkyl, C(=0)(C₃-C₆)cycloalkyl, S(=0)₂(C C₈)alkyl, NR14R15, and oxo, wherein each said substituted-aryl has one or more substituents selected from F, CI, Br, I, CN, NO2, (Ci-C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C

C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo,

wherein said substituted halo(Ci-C₈)alkyl, has one or more substituents selected from CN and NO2, wherein said substituted cyclo(C₃-C₈)alkyl, has one or more substituents selected from CN and N0₂;

(1) R12 is selected from (v), H, F, CI, Br, I, CN, (C C₈)alkyl, halo(C C₈)alkyl, (Ci-C₈)alkoxy, halo(Ci-C₈)alkoxy, and cyclo(C₃-C6)alkyl;

(m) R13 is selected from (v), H, F, CI, Br, I, CN, (C C₈)alkyl, halo(C C₈)alkyl,

(Ci-C₈)alkoxy, and halo(Ci-C₈)alkoxy;

(n) each R14 is independently selected from H, (Ci-C₈)alkyl, (C2-C8)alkenyl, substituted (C C₈)alkyl, halo(C C₈)alkyl, substituted halo(C C₈)alkyl), (C C₈)alkoxy, cyclo(C₃-C6)alkyl, aryl, substituted-aryl, (Ci-C₈)alkyl-aryl, (Ci-C₈)alkyl-(substituted-aryl), O- (Ci-C₈)alkyl-aryl, 0-(Ci-C₈)alkyl-(substituted-aryl), heterocyclyl, substituted-heterocyclyl, (Ci-C₈)alkyl-heterocyclyl, (C C₈)alkyl-(substituted-heterocyclyl), 0-(C C₈)alkyl- heterocyclyl, 0-(C C₈)alkyl-(substituted-heterocyclyl), N(R16)(R17), (C C₈)alkyl- C(=0)N(R16)(R17), C(=0)(C C₈)alkyl, C(=0)(halo(Ci-C₈)alkyl),C(=0)(C₃-C₆)cycloalkyl, (Ci-C₈)alkyl-C(=0)0(Ci-C₈)alkyl, C(=0)H

wherein each said substituted (Ci-C₈)alkyl has one or more substituents selected from CN, and N0₂,

wherein each said substituted halo(Ci-C₈)alkyl), has one or more substituents selected from CN, and N0₂,

wherein each said substituted-aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(Ci-C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo, and

wherein each said substituted-heterocyclyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, (C₃-C₆)cycloalkyl S(C C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (Ci-C₈)alkyl is independently selected), heterocyclyl, C(=0)(C C₈)alkyl, C(=0)0(C C₈)alkyl, and oxo, (wherein said alkyl, alkoxy, and heterocyclyl, may be further substituted with one or more of F, CI, Br, I, CN, and N0₂);

(o) each R15 is independently selected from H, (Ci-C₈)alkyl, (C2-C8)alkenyl, substituted (C C₈)alkyl, halo(C C₈)alkyl, substituted halo(C C₈)alkyl), (C C₈)alkoxy, cyclo(C₃-C6)alkyl, aryl, substituted-aryl, (Ci-C₈)alkyl-aryl, (Ci-C₈)alkyl-(substituted-aryl), O- (Ci-C₈)alkyl-aryl, 0-(Ci-C₈)alkyl-(substituted-aryl), heterocyclyl, substituted-heterocyclyl, (Ci-C₈)alkyl-heterocyclyl, (C C₈)alkyl-(substituted-heterocyclyl), 0-(C C₈)alkyl- heterocyclyl, 0-(C C₈)alkyl-(substituted-heterocyclyl), N(R16)(R17), (C C₈)alkyl- C(=0)N(R16)(R17), C(=0)(C C₈)alkyl, C(=0)(halo(C C₈)alkyl), C(=0)(C₃-C₆)cycloalkyl, (Ci-C₈)alkyl-C(=0)0(Ci-C₈)alkyl, C(=0)H

wherein each said substituted (Ci-C₈)alkyl has one or more substituents selected from CN, and N0₂,

wherein each said substituted halo(Ci-C₈)alkyl), has one or more substituents selected from CN, and N0₂,

wherein each said substituted- aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(Ci-C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo, and

wherein each said substituted-heterocyclyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, (C₃-C₆)cycloalkyl S(C C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (Ci-C₈)alkyl is independently selected), heterocyclyl, C(=0)(C C₈)alkyl, C(=0)0(C C₈)alkyl, and oxo, (wherein said alkyl, alkoxy, and heterocyclyl, may be further substituted with one or more of F, CI, Br, I, CN, and N0₂);

(p) each R16 is independently selected from H, (Ci-C₈)alkyl, substituted-(d- C₈)alkyl, halo(Ci-C₈)alkyl, substituted-halo(Ci-C₈)alkyl, cyclo(C3-C6)alkyl, aryl, substituted- aryl, (C C₈)alkyl-aryl, (C C₈)alkyl-(substituted-aryl), 0-(C C₈)alkyl-aryl, 0-(C C₈)alkyl- (substituted-aryl), heterocyclyl, substituted-heterocyclyl, (Ci-C₈)alkyl-heterocyclyl, (Cr C₈)alkyl-(substituted-heterocyclyl), 0-(C C₈)alkyl-heterocyclyl, 0-(C C₈)alkyl- (substituted-heterocyclyl), 0-(C]-C₈)alkyl

wherein each said substituted (Ci-C₈)alkyl has one or more substituents selected from CN, and N0₂,

wherein each said substituted halo(C]-C₈)alkyl), has one or more substituents selected from CN, and N0₂,

wherein each said substituted-aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(Ci-C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo, and

wherein each said substituted-heterocyclyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo; (q) each R17 is independently selected from H, (Ci-C₈)alkyl, substituted-(d- C₈)alkyl, halo(Ci-C8)alkyl, substituted-halo(Ci-C8)alkyl, cyclo(C3-C6)alkyl, aryl, substituted- aryl, (C C₈)alkyl-aryl, (C C₈)alkyl-(substituted-aryl), 0-(C C₈)alkyl-aryl, 0-(C C₈)alkyl- (substituted-aryl), heterocyclyl, substituted-heterocyclyl, (Ci-C₈)alkyl-heterocyclyl, (Cr C₈)alkyl-(substituted-heterocyclyl), 0-(C C₈)alkyl-heterocyclyl, 0-(C C₈)alkyl- (substituted-heterocyclyl), 0-(Ci-C₈)alkyl

wherein each said substituted (C]-C₈)alkyl has one or more substituents selected from CN, and N0₂,

wherein each said substituted halo(Ci-C₈)alkyl), has one or more substituents selected from CN, and N0₂,

wherein each said substituted- aryl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(Ci-C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo, and

wherein each said substituted-heterocyclyl has one or more substituents selected from F, CI, Br, I, CN, N0₂, (C C₈)alkyl, halo(C C₈)alkyl, (C C₈)alkoxy, halo(C C₈)alkoxy, S(C C₈)alkyl, S(halo(C C₈)alkyl), N((C C₈)alkyl)₂ (wherein each (C C₈)alkyl is independently selected), and oxo;

(r) selected from N and CR12;

(s) selected from N, CR9, and CR13;

(t) X3 is selected from N and CR9; and

(v) R12 and R13 together form a linkage containing 3 to 4 atoms selected from C, N, O, and S, wherein said linkage connects back to the ring to form a 5 to 6 member saturated or unsaturated cyclic ring, wherein said linkage has at least one substituent X4 wherein X4 is selected from R14, N(R14)(R15), N(R14)(C(=0)R14), N(R14)(C(=S)R14),

N(R14)(C(=0)N(R14)(R14)), N(R14)(C(=S)N(R14)(R14)), N(R14)(C(=0)N(R14)((C2- C8)alkenyl)), N(R14)(C(=S)N(R14)((C2-C8)alkenyl)), wherein each R14 is independently selected.

2. A molecule according to claim 1 wherein Rl is selected from H, F, CI, Br, I, CN, N0₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C3)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C6)alkyl, halo(C7)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy,

(C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy,

halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

3. A molecule according to claim 1 wherein R2 is selected from H, F, CI, Br, I, CN, N0₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C3)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C6)alkyl, halo(C7)alkyl, halo(Cs)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy,

(C₆)alkoxy, (C7)alkoxy, (Cs)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy,

halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C6)alkoxy, halo(C7)alkoxy, and halo(Cs)alkoxy.

4. A molecule according to claim 1 wherein R3 is selected from H, F, CI, Br, I, CN, N0₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C6)alkyl, halo(C7)alkyl, halo(Cs)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy,

(C₆)alkoxy, (C7)alkoxy, (Cs)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy,

halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C6)alkoxy, halo(C7)alkoxy, and halo(Cs)alkoxy.

5. A molecule according to claim 1 wherein R4 is selected from H, F, CI, Br, I, CN, N0₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C7)alkyl, halo(Cs)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy,

(C₆)alkoxy, (C7)alkoxy, (Cs)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy,

halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C6)alkoxy, halo(C7)alkoxy, and halo(Cs)alkoxy.

6. A molecule according to claim 1 wherein R5 is selected from H, F, CI, Br, I, CN, N0₂, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C6)alkyl, halo(C7)alkyl, halo(Cs)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy,

(C₆)alkoxy, (C7)alkoxy, (Cs)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy,

halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C6)alkoxy, halo(C7)alkoxy, and halo(Cs)alkoxy.

7. A molecule according to claim 1 wherein R2 and R4 are selected from F, CI, Br, I, CN, and N0₂ and Rl, R3, and R5 are H.

8. A molecule according to claim 1 wherein R2, R3, and R4 are selected from F, CI, Br, I, CN, and N0₂ and Rl, and R5 are H.

9. A molecule according to claim 1 wherein R2, R3, and R4 are independently selected from F and CI and Rland R5 are H.

10. A molecule according to claim 1 wherein Rl is selected from CI and H.

11. A molecule according to claim 1 wherein R2 is selected from CF₃, CH₃, CI, F, and H.

12. A molecule according to claim 1 wherein R3 is selected from OCH₃, CH₃, F, CI, or H.

13. A molecule according to claim 1 wherein R4 is selected from CF₃, CH₃, CI, F, and H.

14. A molecule according to claim 1 wherein R5 is selected from F, CI, and H.

15. A molecule according to claim 1 wherein R6 is selected from halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, and halo(C₈)alkyl.

16. A molecule according to claim 1 wherein R6 is trifluoromethyl.

17. A molecule according to claim 1 wherein R7 is selected from H, F, CI, Br, and I.

18. A molecule according to claim 1 wherein R7 is selected from H, OCH₃, and OH.

19. A molecule according to claim 1 wherein R8 is selected from H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, and halo(C₈)alkyl. 20. A molecule according to claim 1 wherein R8 is selected from CH₃ and H.

21. A molecule according to claim 1 wherein R9 is selected from H, F, CI, Br, I, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

22. A molecule according to claim 1 wherein R10 is selected from H, F, CI, Br, I, CN, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methoxy, ethoxy, (C₃)alkoxy, (C₄)alkoxy, (Cs)alkoxy, (C₆)alkoxy, (C₇)alkoxy, (C₈)alkoxy, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, halo(C₈)alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

23. A molecule according to claim 1 wherein R10 is selected from H, CI, Br, CH₃, and CF₃.

24. A molecule according to claim 1 wherein R10 is selected from Br, C(=NOH)NH₂, C(=0)H, C(=0)NH₂, C(=0)OCH₂CH₃, C(=0)OH, CF₃, CH₂CH₃, CH₂OH, CH3, CI, CN, F, H, NH₂, NHC(=0)H, NHCH₃, N0₂, OCH₃, OCHF₂, and pyridyl.

25. A molecule according to claim 1 wherein Rl 1 is selected from

C(=0)N(H)N(CH₃)(C(=0)CH₂CH₃), C(=0)N(H)N(CH₃)(C(=0)CH₂CF₃),

C(=0)N(H)N(CH₃)(C(=0)cyclopropyl), C(=0)N(H)N(CH₃)(C(=S)CH₂CH₃),

C(=0)N(H)N(CH₃)(C(=0)CH₂CN), C(=0)N(H)N(CH₃)(C(=S)cyclopropyl),

C(=0)N(H)N(CH₃)(C(=0)CH(CF₃)₂), C(=0)N(H)N(CH₃)(C(=0)CF(CF₃)₂),

C(=0)N(H)N(CH₃)(C(=0)CF₂CF₃), and C(=0)N(H)N(CH₃)(C(=0)C≡CCH₃). A molecule according to claim 1 wherein said molecule is selected from

F37

F38

F39

F40

F41

27. A molecule according to claim 1 wherein said molecule is

28. A molecule according to claim 1 wherein said molecule is

FA1

FA2

FA3

FA4

FA5

29. A molecule according to claim 1 wherein R12 is selected from H, F, CI, Br, I, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

30. A molecule according to claim 1 wherein R12 is selected from CH₃ and H.

31. A molecule according to claim 1 wherein R13 is selected from H, F, CI, Br, I, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(C₅)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, halomethoxy, haloethoxy, halo(C₃)alkoxy, halo(C₄)alkoxy, halo(Cs)alkoxy, halo(C₆)alkoxy, halo(C₇)alkoxy, and halo(C₈)alkoxy.

32. A molecule according to claim 1 wherein R13 is selected from CH₃, CI, and H.

33. A molecule according to claim 1 wherein R12-R13 is the hydrocarbyl linkage CH=CHCH=CH.

34. A molecule according to claim 1 wherein R14 and R15 are independently selected from H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C₃)alkyl, halo(C₄)alkyl, halo(Cs)alkyl, halo(C₆)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl- aryl, (C₆)alkyl-aryl, (C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl), ethyl- (substituted-aryl), (C₃)alkyl-(substituted-aryl), (C₄)alkyl-(substituted-aryl), (Cs)alkyl- (substituted-aryl), (C₆)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl), (C₈)alkyl- (substituted-aryl), O-methyl-aryl, O-ethyl-aryl, 0-(C3)alkyl-aryl, 0-(C4)alkyl-aryl, O- (C₅)alkyl-aryl, 0-(C₆)alkyl-aryl, 0-(C₇)alkyl-aryl, 0-(C₈)alkyl-aryl, 0-methyl-(substituted- aryl), O-ethyl-(substituted-aryl), 0-(C3)alkyl-(substituted-aryl), 0-(C4)alkyl-(substituted- aryl), 0-(C₅)alkyl-(substituted-aryl), 0-(C₆)alkyl-(substituted-aryl), 0-(C₇)alkyl-(substituted- aryl), 0-(C₈)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C3)alkyl- heterocyclyl, (C4)alkyl-heterocyclyl, (Cs)alkyl-heterocyclyl, (C6)alkyl-heterocyclyl,

(C7)alkyl-heterocyclyl, (C₈)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl- (substituted-heterocyclyl), (C3)alkyl-(substituted-heterocyclyl), (C4)alkyl-(substituted- heterocyclyl), (Cs)alkyl-(substituted-heterocyclyl), (C6)alkyl-(substituted-heterocyclyl), (C7)alkyl-(substituted-heterocyclyl), (C8)alkyl-(substituted-heterocyclyl), O-methyl- heterocyclyl, O-ethyl-heterocyclyl, 0-(C3)alkyl-heterocyclyl, 0-(C4)alkyl-heterocyclyl, O- (C₅)alkyl-heterocyclyl, 0-(C₆)alkyl-heterocyclyl, 0-(C₇)alkyl-heterocyclyl, 0-(C₈)alkyl- heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O- (C3)alkyl-(substituted-heterocyclyl), 0-(C4)alkyl-(substituted-heterocyclyl), 0-(Cs)alkyl- (substituted-heterocyclyl), 0-(C6)alkyl-(substituted-heterocyclyl), 0-(C₇)alkyl-(substituted- heterocyclyl), 0-(C₈)alkyl-(substituted-heterocyclyl), methyl-C(=0)N(R16)(R17), ethyl- C(=0)N(R16)(R17), (C₃)alkyl-C(=0)N(R16)(R17), (C₄)alkyl-C(=0)N(R16)(R17), (C₅)alkyl- C(=0)N(R16)(R17), (C₆)alkyl-C(=0)N(R16)(R17), (C₇)alkyl-C(=0)N(R16)(R17), and (C₈)alkyl-C(=0)N(R16)(R17).

35. A molecule according to claim 1 wherein R14 and R15 are independently selected from H, CH₃, CH₂CF₃, CH₂-halopyridyl, oxo-pyrrolidinyl, halophenyl, thietanyl, CH₂- phenyl, CH₂-pyridyl, thietanyl-dioxide, CH₂-halothiazolyl, C((CH₃)₂)-pyridyl,

N(H) (halophenyl), CH₂-pyrimidinyl, CH₂-tetrahydrofuranyl, CH₂-furanyl, 0-CH₂- halopyridyl, and CH₂C(=0)N(H)(CH₂CF₃).

36. A molecule according to claim 1 wherein R16 and R17 are independently selected from H, methyl, ethyl, (C₃)alkyl, (C₄)alkyl, (C₅)alkyl, (C₆)alkyl, (C₇)alkyl, (C₈)alkyl, halomethyl, haloethyl, halo(C3)alkyl, halo(C4)alkyl, halo(Cs)alkyl, halo(C6)alkyl, halo(C₇)alkyl, halo(C₈)alkyl, methyl-aryl, ethyl-aryl, (C₃)alkyl-aryl, (C₄)alkyl-aryl, (C₅)alkyl- aryl, (C₆)alkyl-aryl, (C₇)alkyl-aryl, (C₈)alkyl-aryl, methyl-(substituted-aryl), ethyl- (substituted-aryl), (C3)alkyl-(substituted-aryl), (C4)alkyl-(substituted-aryl), (Cs)alkyl- (substituted-aryl), (C6)alkyl-(substituted-aryl), (C₇)alkyl-(substituted-aryl), (C₈)alkyl- (substituted-aryl), O-methyl-aryl, O-ethyl-aryl, 0-(C3)alkyl-aryl, 0-(C4)alkyl-aryl, O- (C₅)alkyl-aryl, 0-(C₆)alkyl-aryl, 0-(C₇)alkyl-aryl, 0-(C₈)alkyl-aryl, 0-methyl-(substituted- aryl), O-ethyl-(substituted-aryl), 0-(C3)alkyl-(substituted-aryl), 0-(C4)alkyl-(substituted- aryl), 0-(C₅)alkyl-(substituted-aryl), 0-(C₆)alkyl-(substituted-aryl), 0-(C₇)alkyl-(substituted- aryl), 0-(Cs)alkyl-(substituted-aryl), methyl-heterocyclyl, ethyl-heterocyclyl, (C3)alkyl- heterocyclyl, (C4)alkyl-heterocyclyl, (Cs)alkyl-heterocyclyl, (C6)alkyl-heterocyclyl, (C7)alkyl-heterocyclyl, (C8)alkyl-heterocyclyl, methyl-(substituted-heterocyclyl), ethyl- (substituted-heterocyclyl), (C3)alkyl-(substituted-heterocyclyl), (C4)alkyl-(substituted- heterocyclyl), (C5)alkyl-(substituted-heterocyclyl), (C6)alkyl-(substituted-heterocyclyl), (C7)alkyl-(substituted-heterocyclyl), (C8)alkyl-(substituted-heterocyclyl), O-methyl- heterocyclyl, O-ethyl-heterocyclyl, 0-(C3)alkyl-heterocyclyl, 0-(C4)alkyl-heterocyclyl, O- (C₅)alkyl-heterocyclyl, 0-(C₆)alkyl-heterocyclyl, 0-(C₇)alkyl-heterocyclyl, 0-(C₈)alkyl- heterocyclyl, O-methyl-(substituted-heterocyclyl), O-ethyl-(substituted-heterocyclyl), O- (C3)alkyl-(substituted-heterocyclyl), 0-(C4)alkyl-(substituted-heterocyclyl), 0-(Cs)alkyl- (substituted-heterocyclyl), 0-(C6)alkyl-(substituted-heterocyclyl), 0-(C7)alkyl-(substituted- heterocyclyl), and 0-(Cs)alkyl-(substituted-heterocyclyl).

37. A molecule according to claim 1 wherein R16 and R17 are independently selected from H, CH₂CF₃, cyclopropyl, thietanyl, thietanyl dioxide, and halophenyl.

38. A molecule according to claim 1 wherein XI is CR12, X2 is CR13, and X3 is CR9.

39. A molecule according to claim 1 wherein said molecule is

40. A molecule according to claim 1 wherein

R2, R3, and R4 are independently selected from F and CI;

Rl, R5, R7, and R8 are H; and

R6 is trifluoromethyl.

41. A composition according to claim 1 further comprising:

(a) one or more compounds having acaricidal, algicidal, avicidal, bactericidal, fungicidal, herbicidal, insecticidal, molluscicidal, nematicidal, rodenticidal, or virucidal properties; or

(b) one or more compounds that are antifeedants, bird repellents, chemosterilants, herbicide safeners, insect attractants, insect repellents, mammal repellents, mating disrupters, plant activators, plant growth regulators, or synergists; or

(c) both (a) and (b).

42. A composition according to claim 1 wherein further comprising one or more compounds selected from: (3 -ethoxypropyl)mercury bromide, 1,2-dichloropropane, 1,3- dichloropropene, 1-methylcyclopropene, 1-naphthol, 2-(octylthio)ethanol, 2,3,5-tri- iodobenzoic acid, 2,3,6-TBA, 2,3,6-TBA-dimethylammonium, 2,3,6-TBA-lithium, 2,3,6- TBA-potassium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-T-2-butoxypropyl, 2,4,5-T-2-ethylhexyl, 2,4,5-T-3-butoxypropyl, 2,4,5-TB, 2,4,5-T-butometyl, 2,4,5-T-butotyl, 2,4,5-T-butyl, 2,4,5- T-isobutyl, 2,4,5-T-isoctyl, 2,4,5-T-isopropyl, 2,4,5-T-methyl, 2,4,5-T-pentyl, 2,4,5-T- sodium, 2,4,5-T-triethylammonium, 2,4,5-T-trolamine, 2,4-D, 2,4-D-2-butoxypropyl, 2,4-D- 2-ethylhexyl, 2,4-D-3-butoxypropyl, 2,4-D-ammonium, 2,4-DB, 2,4-DB-butyl, 2,4-DB- dimethylammonium, 2,4-DB-isoctyl, 2,4-DB -potassium, 2,4-DB-sodium, 2,4-D-butotyl, 2,4- D-butyl, 2,4-D-diethylammonium, 2,4-D-dimethylammonium, 2,4-D-diolamine, 2,4-D- dodecylammonium, 2,4-DEB, 2,4-DEP, 2,4-D-ethyl, 2,4-D-heptylammonium, 2,4-D- isobutyl, 2,4-D-isoctyl, 2,4-D-isopropyl, 2,4-D-isopropylammonium, 2,4-D-lithium, 2,4-D- meptyl, 2,4-D-methyl, 2,4-D-octyl, 2,4-D-pentyl, 2,4-D-potassium, 2,4-D-propyl, 2,4-D- sodium, 2,4-D-tefuryl, 2,4-D-tetradecylammonium, 2,4-D-triethylammonium, 2,4-D-tris(2- hydroxypropyl)ammonium, 2,4-D-trolamine, 2iP, 2-methoxyethylmercury chloride, 2- phenylphenol, 3,4-DA, 3,4-DB, 3,4-DP, 4-aminopyridine, 4-CPA, 4-CPA-potassium, 4-CPA- sodium, 4-CPB, 4-CPP, 4-hydroxyphenethyl alcohol, 8 -hydroxy quinoline sulfate, 8- phenylmercurioxyquinoline, abamectin, abscisic acid, ACC, acephate, acequinocyl, acetamiprid, acethion, acetochlor, acetophos, acetoprole, acibenzolar, acibenzolar-S-methyl, acifluorfen, acifluorfen-methyl, acifluorf en- sodium, aclonifen, acrep, acrinathrin, acrolein, acrylonitrile, acypetacs, acypetacs-copper, acypetacs-zinc, alachlor, alanycarb, albendazole, aldicarb, aldimorph, aldoxycarb, aldrin, allethrin, allicin, allidochlor, allosamidin, alloxydim, alloxydim-sodium, allyl alcohol, allyxycarb, alorac, α/ρΛα-cypermethrin, α/ρ ζα-endosulfan, ametoctradin, ametridione, ametryn, amibuzin, amicarbazone, amicarthiazol, amidithion, amidoflumet, amidosulfuron, aminocarb, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, aminopyralid, aminopyralid-potassium, aminopyralid-tris(2- hydroxypropyl)ammonium, amiprofos-methyl, amiprophos, amisulbrom, amiton, amiton oxalate, amitraz, amitrole, ammonium sulfamate, ammonium a-naphthaleneacetate, amobam, ampropylfos, anabasine, ancymidol, anilazine, anilofos, anisuron, anthraquinone, antu, apholate, aramite, arsenous oxide, asomate, aspirin, asulam, asulam-potassium, asulam- sodium, athidathion, atraton, atrazine, aureofungin, aviglycine, aviglycine hydrochloride, azaconazole, azadirachtin, azafenidin, azamethiphos, azimsulfuron, azinphos-ethyl, azinphos- methyl, aziprotryne, azithiram, azobenzene, azocyclotin, azothoate, azoxystrobin, bachmedesh, barban, barium hexafluorosilicate, barium polysulfide, barthrin, BCPC, beflubutamid, benalaxyl, benalaxyl-M, benazolin, benazolin-dimethylammonium, benazolin- ethyl, benazolin-potassium, bencarbazone, benclothiaz, bendiocarb, benfluralin, benfuracarb, benfuresate, benodanil, benomyl, benoxacor, benoxafos, benquinox, bensulfuron, bensulfuron-methyl, bensulide, bensultap, bentaluron, bentazone, bentazone- sodium, benthiavalicarb, benthiavalicarb-isopropyl, benthiazole, bentranil, benzadox, benzadox- ammonium, benzalkonium chloride, benzamacril, benzamacril-isobutyl, benzamorf, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzohydroxamic acid, benzoximate, benzoylprop, benzoylprop-ethyl, benzthiazuron, benzyl benzoate,

benzyladenine, berberine, berberine chloride, ^eta-cyfluthrin, ^eto-cypermethrin, bethoxazin, bicyclopyrone, bifenazate, bifenox, bifenthrin, bifujunzhi, bilanafos, bilanafos-sodium, binapacryl, bingqingxiao, bioallethrin, bioethanomethrin, biopermethrin, bioresmethrin, biphenyl, bisazir, bismerthiazol, bispyribac, bispyribac-sodium, bistrifluron, bitertanol, bithionol, bixafen, blasticidin-S, borax, Bordeaux mixture, boric acid, boscalid, brassinolide, brassinolide-ethyl, brevicomin, brodifacoum, brofenvalerate, brofluthrinate, bromacil, bromacil-lithium, bromacil-sodium, bromadiolone, bromethalin, bromethrin, bromfenvinfos, bromoacetamide, bromobonil, bromobutide, bromocyclen, bromo-DDT, bromofenoxim, bromophos, bromophos-ethyl, bromopropylate, bromothalonil, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium,

brompyrazon, bromuconazole, bronopol, bucarpolate, bufencarb, buminafos, bupirimate, buprofezin, Burgundy mixture, busulfan, butacarb, butachlor, butafenacil, butamifos, butathiofos, butenachlor, butethrin, buthidazole, buthiobate, buthiuron, butocarboxim, butonate, butopyronoxyl, butoxycarboxim, butralin, butroxydim, buturon, butylamine, butylate, cacodylic acid, cadusafos, cafenstrole, calcium arsenate, calcium chlorate, calcium cyanamide, calcium polysulfide, calvinphos, cambendichlor, camphechlor, camphor, captafol, captan, carbamorph, carbanolate, carbaryl, carbasulam, carbendazim, carbendazim benzenesulfonate, carbendazim sulfite, carbetamide, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, carboxazole, carboxide, carboxin, carfentrazone, carfentrazone-ethyl, carpropamid, cartap, cartap hydrochloride, carvacrol, carvone, CDEA, cellocidin, CEPC, ceralure, Cheshunt mixture, chinomethionat, chitosan, chlobenthiazone, chlomethoxyfen, chloralose, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, chloramben-methylammonium, chloramben-sodium, chloramine phosphorus, chloramphenicol, chloraniformethan, chloranil, chloranocryl, chlorantraniliprole, chlorazifop, chlorazifop-propargyl, chlorazine, chlorbenside, chlorbenzuron, chlorbicyclen, chlorbromuron, chlorbufam, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorempenthrin, chlorethoxyfos, chloreturon, chlorfenac, chlorfenac- ammonium, chlorfenac-sodium, chlorfenapyr, chlorfenazole, chlorfenethol, chlorfenprop, chlorfenson, chlorfensulphide, chlorfenvinphos, chlorfluazuron, chlorflurazole, chlorfluren, chlorfluren-methyl, chlorflurenol, chlorflurenol-methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlormephos, chlormequat, chlormequat chloride, chlornidine, chlornitrofen, chlorobenzilate, chlorodinitronaphthalenes, chloroform, chloromebuform, chloromethiuron, chloroneb, chlorophacinone, chlorophacinone-sodium, chloropicrin, chloropon, chloropropylate, chlorothalonil, chlorotoluron, chloroxuron, chloroxynil, chlorphonium, chlorphonium chloride, chlorphoxim, chlorprazophos, chlorprocarb, chlorpropham, chlorpyrifos, chlorpyrifos-methyl, chlorquinox, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, chlorthiophos, chlozolinate, choline chloride, chromafenozide, cinerin I, cinerin II, cinerins, cinidon-ethyl, cinmethylin, cinosulfuron, ciobutide, cisanilide, cismethrin, clethodim, climbazole, cliodinate, clodinafop, clodinafop-propargyl, cloethocarb, clofencet, clofencet-potassium, clofentezine, clofibric acid, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, clopyralid-methyl, clopyralid-olamine, clopyralid-potassium, clopyralid-tris(2- hydroxypropyl)ammonium, cloquintocet, cloquintocet-mexyl, cloransulam, cloransulam- methyl, closantel, clothianidin, clotrimazole, cloxyfonac, cloxyfonac-sodium, CMA, codlelure, colophonate, copper acetate, copper acetoarsenite, copper arsenate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, coumachlor, coumafuryl, coumaphos, coumatetralyl, coumithoate, coumoxystrobin, CPMC, CPMF, CPPC, credazine, cresol, crimidine, crotamiton, crotoxyphos, crufomate, cryolite, cue-lure, cufraneb, cumyluron, cuprobam, cuprous oxide, curcumenol, cyanamide, cyanatryn, cyanazine, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyazofamid, cybutryne, cyclafuramid, cyclanilide, cyclethrin, cycloate, cycloheximide, cycloprate, cycloprothrin, cyclosulfamuron, cycloxaprid, cycloxydim, cycluron, cyenopyrafen, cyflufenamid, cyflumetofen, cyfluthrin, cyhalofop, cyhalofop-butyl, cyhalothrin, cyhexatin, cymiazole, cymiazole hydrochloride, cymoxanil, cyometrinil, cypendazole, cypermethrin, cyperquat, cyperquat chloride, cyphenothrin, cyprazine, cyprazole, cyproconazole, cyprodinil, cyprofuram, cypromid, cyprosulfamide, cyromazine, cythioate, daimuron, dalapon, dalapon-calcium, dalapon-magnesium, dalapon- sodium, daminozide, dayoutong, dazomet, dazomet-sodium, DBCP, J-camphor, DCIP, DCPTA, DDT, debacarb, decafentin, decarbofuran, dehydroacetic acid, delachlor, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton- O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton- S-methylsulphon, desmedipham, desmetryn, J-fanshiluquebingjuzhi, diafenthiuron, dialifos, di-allate, diamidafos, diatomaceous earth, diazinon, dibutyl phthalate, dibutyl succinate, dicamba, dicamba-diglycolamine, dicamba-dimethylammonium, dicamba-diolamine, dicamba- isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba- sodium, dicamba-trolamine, dicapthon, dichlobenil, dichlofenthion, dichlofluanid, dichlone, dichloralurea, dichlorbenzuron, dichlorflurenol, dichlorflurenol-methyl, dichlormate, dichlormid, dichlorophen, dichlorprop, dichlorprop-2-ethylhexyl, dichlorprop-butotyl, dichlorprop-dimethylammonium, dichlorprop-ethylammonium, dichlorprop-isoctyl, dichlorprop-methyl, dichlorprop-P, dichlorprop-P-2-ethylhexyl, dichlorprop-P- dimethylammonium, dichlorprop-potassium, dichlorprop-sodium, dichlorvos, dichlozoline, diclobutrazol, diclocymet, diclofop, diclofop-methyl, diclomezine, diclomezine-sodium, dicloran, diclosulam, dicofol, dicoumarol, dicresyl, dicrotophos, dicyclanil, dicyclonon, dieldrin, dienochlor, diethamquat, diethamquat dichloride, diethatyl, diethatyl-ethyl, diethofencarb, dietholate, diethyl pyrocarbonate, diethyltoluamide, difenacoum,

difenoconazole, difenopenten, difenopenten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, difethialone, diflovidazin, diflubenzuron, diflufenican, diflufenzopyr, diflufenzopyr-sodium, diflumetorim, dikegulac, dikegulac-sodium, dilor, dimatif, dimefluthrin, dimefox, dimefuron, dimepiperate, dimetachlone, dimetan, dimethacarb, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimethipin, dimethirimol, dimethoate, dimethomorph, dimethrin, dimethyl carbate, dimethyl phthalate,

dimethylvinphos, dimetilan, dimexano, dimidazon, dimoxystrobin, dinex, dinex-diclexine, dingjunezuo, diniconazole, diniconazole-M, dinitramine, dinobuton, dinocap, dinocap-4, dinocap-6, dinocton, dinofenate, dinopenton, dinoprop, dinosam, dinoseb, dinoseb acetate, dinoseb-ammonium, dinoseb-diolamine, dinoseb-sodium, dinoseb-trolamine, dinosulfon, dinotefuran, dinoterb, dinoterb acetate, dinoterbon, diofenolan, dioxabenzofos, dioxacarb, dioxathion, diphacinone, diphacinone-sodium, diphenamid, diphenyl sulfone, diphenylamine, dipropalin, dipropetryn, dipyrithione, diquat, diquat dibromide, disparlure, disul, disulfiram, disulfoton, disul-sodium, ditalimfos, dithianon, dithicrofos, dithioether, dithiopyr, diuron, d- limonene, DMPA, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, dodemorph, dodemorph acetate, dodemorph benzoate, dodicin, dodicin hydrochloride, dodicin-sodium, dodine, dofenapyn, dominicalure, doramectin, drazoxolon, DSMA, dufulin, EBEP, EBP, ecdysterone, edifenphos, eglinazine, eglinazine-ethyl, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothal, endothal-diammonium, endothal- dipotassium, endothal-disodium, endothion, endrin, enestroburin, EPN, epocholeone, epofenonane, epoxiconazole, eprinomectin, epronaz, EPTC, erbon, ergocalciferol, erlujixiancaoan, esdepallethrine, esfenvalerate, esprocarb, etacelasil, etaconazole, etaphos, etem, ethaboxam, ethachlor, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethaprochlor, ethephon, ethidimuron, ethiofencarb, ethiolate, ethion, ethiozin, ethiprole, ethirimol, ethoate-methyl, ethofumesate, ethohexadiol, ethoprophos, ethoxyfen, ethoxyfen- ethyl, ethoxyquin, ethoxysulfuron, ethychlozate, ethyl formate, ethyl a-naphthaleneacetate, ethyl-DDD, ethylene, ethylene dibromide, ethylene dichloride, ethylene oxide, ethylicin, ethylmercury 2,3-dihydroxypropyl mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etinofen, etnipromid, etobenzanid, etofenprox, etoxazole, etridiazole, etrimfos, eugenol, EXD, famoxadone, famphur, fenamidone, fenaminosulf, fenamiphos, fenapanil, fenarimol, fenasulam, fenazaflor, fenazaquin, fenbuconazole, fenbutatin oxide, fenchlorazole, fenchlorazole-ethyl,

fenchlorphos, fenclorim, fenethacarb, fenfluthrin, fenfuram, fenhexamid, fenitropan, fenitrothion, fenjuntong, fenobucarb, fenoprop, fenoprop-3-butoxypropyl, fenoprop- butometyl, fenoprop-butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop- potassium, fenothiocarb, fenoxacrim, fenoxanil, fenoxaprop, fenoxaprop-ethyl, fenoxaprop-P, fenoxaprop-P-ethyl, fenoxasulfone, fenoxycarb, fenpiclonil, fenpirithrin, fenpropathrin, fenpropidin, fenpropimorph, fenpyrazamine, fenpyroximate, fenridazon, fenridazon- potassium, fenridazon-propyl, fenson, fensulfothion, fenteracol, fenthiaprop, fenthiaprop- ethyl, fenthion, fenthion-ethyl, fentin, fentin acetate, fentin chloride, fentin hydroxide, fentrazamide, fentrifanil, fenuron, fenuron TCA, fenvalerate, ferbam, ferimzone, ferrous sulfate, fipronil, flamprop, flamprop-isopropyl, flamprop-M, flamprop-methyl, flamprop-M- isopropyl, flamprop-M-methyl, flazasulfuron, flocoumafen, flometoquin, flonicamid, florasulam, fluacrypyrim, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop- P-butyl, fluazinam, fluazolate, fluazuron, flubendiamide, flubenzimine, flucarbazone, flucarbazone-sodium, flucetosulfuron, fluchloralin, flucofuron, flucycloxuron, flucythrinate, fludioxonil, fluenetil, fluensulfone, flufenacet, flufenerim, flufenican, flufenoxuron, flufenprox, flufenpyr, flufenpyr-ethyl, flufiprole, flumethrin, flumetover, flumetralin, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, flumorph, fluometuron, fluopicolide, fluopyram, fluorbenside, fluoridamid, fluoroacetamide, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoroimide, fluoromidine, fluoronitrofen, fluothiuron, fluotrimazole, fluoxastrobin, flupoxam, flupropacil, flupropadine, flupropanate, flupropanate-sodium, flupyradifurone, flupyrsulfuron, flupyrsulfuron-methyl, flupyrsulfuron- methyl-sodium, fluquinconazole, flurazole, flurenol, flurenol-butyl, flurenol-methyl, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr-meptyl,

flurprimidol, flursulamid, flurtamone, flusilazole, flusulfamide, fluthiacet, fluthiacet-methyl, flutianil, flutolanil, flutriafol, fluvalinate, fluxapyroxad, fluxofenim, folpet, fomesafen, fomesafen-sodium, fonofos, foramsulfuron, forchlorfenuron, formaldehyde, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosamine, fosamine-ammonium, fosetyl, fosetyl-aluminium, fosmethilan, fospirate, fosthiazate, fosthietan, frontalin, fuberidazole, fucaojing, fucaomi, funaihecaoling, fuphenthiourea, furalane, furalaxyl, furamethrin, furametpyr, furathiocarb, furcarbanil, furconazole, furconazole-cis, furethrin, furfural, furilazole, furmecyclox, furophanate, furyloxyfen, gamma-cyhalothrin, gamma-HCR, genit, gibberellic acid, gibberellins, gliftor, glufosinate, glufosinate-ammonium, glufosinate-P, glufosinate-P-ammonium, glufosinate-P-sodium, glyodin, glyoxime, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate-isopropylammonium, glyphosate-monoammonium, glyphosate-potassium, glyphosate-sesquisodium, glyphosate-trimesium, glyphosine, gossyplure, grandlure, griseofulvin, guazatine, guazatine acetates, halacrinate, halfenprox, halofenozide, halosafen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop- methyl, haloxyfop-P, haloxyfop-P-etotyl, haloxyfop-P-methyl, haloxyfop-sodium, HCH, hemel, hempa, HEOD, heptachlor, heptenophos, heptopargil, heterophos, hexachloroacetone, hexachlorobenzene, hexachlorobutadiene, hexachlorophene, hexaconazole, hexaflumuron, hexaflurate, hexalure, hexamide, hexazinone, hexylthiofos, hexythiazox, HHDN, holosulf, huancaiwo, huangcaoling, huanjunzuo, hydramethylnon, hydrargaphen, hydrated lime, hydrogen cyanide, hydroprene, hymexazol, hyquincarb, IAA, IBA, icaridin, imazalil, imazalil nitrate, imazalil sulfate, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox- ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin-ammonium, imazaquin-methyl, imazaquin- sodium, imazethapyr, imazethapyr-ammonium, imazosulfuron, imibenconazole, imicyafos, imidacloprid, imidaclothiz, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, imiprothrin, inabenfide, indanofan, indaziflam, indoxacarb, inezin, iodobonil, iodocarb, iodomethane, iodosulfuron, iodosulfuron-methyl, iodosulfuron-methyl-sodium, iofensulfuron,

iofensulfuron-sodium, ioxynil, ioxynil octanoate, ioxynil-lithium, ioxynil-sodium, ipazine, ipconazole, ipfencarbazone, iprobenfos, iprodione, iprovalicarb, iprymidam, ipsdienol, ipsenol, IPSP, isamidofos, isazofos, isobenzan, isocarbamid, isocarbophos, isocil, isodrin, isofenphos, isofenphos-methyl, isolan, isomethiozin, isonoruron, isopolinate, isoprocarb, isopropalin, isoprothiolane, isoproturon, isopyrazam, isopyrimol, isothioate, isotianil, isouron, isovaledione, isoxaben, isoxachlortole, isoxadifen, isoxadifen-ethyl, isoxaflutole, isoxapyrifop, isoxathion, ivermectin, izopamfos, japonilure, japothrins, jasmolin I, jasmolin II, jasmonic acid, jiahuangchongzong, jiajizengxiaolin, jiaxiangjunzhi, jiecaowan, jiecaoxi, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kadethrin, karbutilate, karetazan, karetazan-potassium, kasugamycin, kasugamycin hydrochloride, kejunlin, kelevan, ketospiradox, ketospiradox-potassium, kinetin, kinoprene, kresoxim- methyl, kuicaoxi, lactofen, lambda-cyhalothrin, latilure, lead arsenate, lenacil, lepimectin, leptophos, lindane, lineatin, linuron, lirimfos, litlure, looplure, lufenuron, lvdingjunzhi, lvxiancaolin, lythidathion, MAA, malathion, maleic hydrazide, malonoben, maltodextrin, MAMA, mancopper, mancozeb, mandipropamid, maneb, matrine, mazidox, MCPA, MCPA- 2-ethylhexyl, MCPA-butotyl, MCPA-butyl, MCPA-dimethylammonium, MCPA-diolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA- olamine, MCPA-potassium, MCPA-sodium, MCPA-thioethyl, MCPA-trolamine, MCPB, MCPB-ethyl, MCPB -methyl, MCPB-sodium, mebenil, mecarbam, mecarbinzid, mecarphon, mecoprop, mecoprop-2-ethylhexyl, mecoprop-dimethylammonium, mecoprop-diolamine, mecoprop-ethadyl, mecoprop-isoctyl, mecoprop-methyl, mecoprop-P, mecoprop-P-2- ethylhexyl, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop-potassium, mecoprop-P-potassium, mecoprop- sodium, mecoprop-trolamine, medimeform, medinoterb, medinoterb acetate, medlure, mefenacet, mefenpyr, mefenpyr-diethyl, mefluidide, mefluidide-diolamine, mefluidide-potassium, megatomoic acid, menazon, mepanipyrim, meperfluthrin, mephenate, mephosfolan, mepiquat, mepiquat chloride, mepiquat pentaborate, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, merphos, mesoprazine, mesosulfuron, mesosulfuron-methyl, mesotrione, mesulfen, mesulfenfos, metaflumizone, metalaxyl, metalaxyl-M, metaldehyde, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, metazoxolon, metconazole, metepa, metflurazon, methabenzthiazuron, methacrifos, methalpropalin, methamidophos, methasulfocarb, methazole, methfuroxam, methidathion, methiobencarb, methiocarb, methiopyrisulfuron, methiotepa, methiozolin, methiuron, methocrotophos, methometon, methomyl, methoprene, methoprotryne, methoquin-butyl, methothrin, methoxychlor, methoxyfenozide, methoxyphenone, methyl apholate, methyl bromide, methyl eugenol, methyl iodide, methyl isothiocyanate, methylacetophos, methylchloroform, methyldymron, methylene chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide,

methylneodecanamide, metiram, metobenzuron, metobromuron, metofluthrin, metolachlor, metolcarb, metominostrobin, metosulam, metoxadiazone, metoxuron, metrafenone, metribuzin, metsulfovax, metsulfuron, metsulfuron-methyl, mevinphos, mexacarbate, mieshuan, milbemectin, milbemycin oxime, milneb, mipafox, mirex, MNAF, moguchun, molinate, molosultap, monalide, monisouron, monochloroacetic acid, monocrotophos, monolinuron, monosulfuron, monosulfuron-ester, monuron, monuron TCA, morfamquat, morfamquat dichloride, moroxydine, moroxydine hydrochloride, morphothion, morzid, moxidectin, MSMA, muscalure, myclobutanil, myclozolin, N-(ethylmercury)-p- toluenesulphonanilide, nabam, naftalofos, naled, naphthalene, naphthaleneacetamide, naphthalic anhydride, naphthoxyacetic acids, naproanilide, napropamide, naptalam, naptalam-sodium, natamycin, neburon, niclosamide, niclosamide-olamine, nicosulfuron, nicotine, nifluridide, nipyraclofen, nitenpyram, nithiazine, nitralin, nitrapyrin, nitrilacarb, nitrofen, nitrofluorfen, nitrostyrene, nitrothal-isopropyl, norbormide, norflurazon, nornicotine, noruron, novaluron, noviflumuron, nuarimol, OCH, octachlorodipropyl ether, octhilinone, ofurace, omethoate, orbencarb, orfralure, ortho-dichlorobenzene,

orthosulfamuron, oryctalure, orysastrobin, oryzalin, osthol, ostramone, oxabetrinil, oxadiargyl, oxadiazon, oxadixyl, oxamate, oxamyl, oxapyrazon, oxapyrazon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxine-copper, oxolinic acid,

oxpoconazole, oxpoconazole fumarate, oxycarboxin, oxydemeton-methyl, oxydeprofos, oxydisulfoton, oxyfluorfen, oxymatrine, oxytetracycline, oxytetracycline hydrochloride, paclobutrazol, paichongding, para-dichlorobenzene, parafluron, paraquat, paraquat dichloride, paraquat dimetilsulfate, parathion, parathion-methyl, parinol, pebulate, pefurazoate, pelargonic acid, penconazole, pencycuron, pendimethalin, penflufen, penfluron, penoxsulam, pentachlorophenol, pentanochlor, penthiopyrad, pentmethrin, pentoxazone, perfluidone, permethrin, pethoxamid, phenamacril, phenazine oxide, phenisopham, phenkapton, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenothrin, phenproxide, phenthoate, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride,

phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, phorate, phosacetim, phosalone, phosdiphen, phosfolan, phosfolan-methyl, phosglycin, phosmet, phosnichlor, phosphamidon, phosphine, phosphocarb, phosphorus, phostin, phoxim, phoxim-methyl, phthalide, picloram, picloram-2-ethylhexyl, picloram-isoctyl, picloram- methyl, picloram-olamine, picloram-potassium, picloram-triethylammonium, picloram-tris(2- hydroxypropyl)ammonium, picolinafen, picoxystrobin, pindone, pindone- sodium, pinoxaden, piperalin, piperonyl butoxide, piperonyl cyclonene, piperophos, piproctanyl, piproctanyl bromide, piprotal, pirimetaphos, pirimicarb, pirimioxyphos, pirimiphos-ethyl, pirimiphos- methyl, plifenate, polycarbamate, polyoxins, polyoxorim, polyoxorim-zinc, polythialan, potassium arsenite, potassium azide, potassium cyanate, potassium gibberellate, potassium naphthenate, potassium polysulfide, potassium thiocyanate, potassium a-naphthaleneacetate, ρρ'-ΌΌΎ, prallethrin, precocene I, precocene II, precocene III, pretilachlor, primidophos, primisulfuron, primisulfuron-methyl, probenazole, prochloraz, prochloraz-manganese, proclonol, procyazine, procymidone, prodiamine, profenofos, profluazol, profluralin, profluthrin, profoxydim, proglinazine, proglinazine-ethyl, prohexadione, prohexadione- calcium, prohydrojasmon, promacyl, promecarb, prometon, prometryn, promurit, propachlor, propamidine, propamidine dihydrochloride, propamocarb, propamocarb hydrochloride, propanil, propaphos, propaquizafop, propargite, proparthrin, propazine, propetamphos, propham, propiconazole, propineb, propisochlor, propoxur, propoxycarbazone, propoxycarbazone-sodium, propyl isome, propyrisulfuron, propyzamide, proquinazid, prosuler, prosulfalin, prosulfocarb, prosulfuron, prothidathion, prothiocarb, prothiocarb hydrochloride, prothioconazole, prothiofos, prothoate, protrifenbute, proxan, proxan-sodium, prynachlor, pydanon, pymetrozine, pyracarbolid, pyraclofos, pyraclonil, pyraclostrobin, pyraflufen, pyraflufen-ethyl, pyrafluprole, pyramat, pyrametostrobin, pyraoxystrobin, pyrasulfotole, pyrazolynate, pyrazophos, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazothion, pyrazoxyfen, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyribambenz-isopropyl, pyribambenz-propyl, pyribencarb, pyribenzoxim, pyributicarb, pyriclor, pyridaben, pyridafol, pyridalyl, pyridaphenthion, pyridate, pyridinitril, pyrifenox, pyrifluquinazon, pyriftalid, pyrimethanil, pyrimidifen, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrimitate, pyrinuron, pyriofenone, pyriprole, pyripropanol, pyriproxyfen, pyrithiobac, pyrithiobac- sodium, pyrolan, pyroquilon, pyroxasulfone, pyroxsulam, pyroxychlor, pyroxyfur, quassia, quinacetol, quinacetol sulfate, quinalphos, quinalphos-methyl, quinazamid, quinclorac, quinconazole, quinmerac, quinoclamine, quinonamid, quinothion, quinoxyfen, quintiofos, quintozene, quizalofop, quizalofop-ethyl, quizalofop-P, quizalofop-P-ethyl, quizalofop-P- tefuryl, quwenzhi, quyingding, rabenzazole, rafoxanide, rebemide, resmethrin, rhodethanil, rhodojaponin-III, ribavirin, rimsulfuron, rotenone, ryania, saflufenacil, saijunmao, saisentong, salicylanilide, sanguinarine, santonin, schradan, scilliroside, sebuthylazine, secbumeton, sedaxane, selamectin, semiamitraz, semiamitraz chloride, sesamex, sesamolin, sethoxydim, shuangjiaancaolin, siduron, siglure, silafluofen, silatrane, silica gel, silthiofam, simazine, simeconazole, simeton, simetryn, sintofen, SMA, S-metolachlor, sodium arsenite, sodium azide, sodium chlorate, sodium fluoride, sodium fluoroacetate, sodium hexafluorosilicate, sodium naphthenate, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, sodium thiocyanate, sodium a-naphthaleneacetate, sophamide, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, spiroxamine, streptomycin, streptomycin sesquisulfate, strychnine, sulcatol, sulcofuron, sulcofuron-sodium, sulcotrione, sulfallate, sulfentrazone, sulfiram, sulfluramid, sulfometuron, sulfometuron-methyl, sulfosulfuron, sulfotep, sulfoxaflor, sulfoxide, sulfoxime, sulfur, sulfuric acid, sulfuryl fluoride, sulglycapin, sulprofos, sultropen, swep, toi/-fluvalinate, tavron, tazimcarb, TCA, TCA-ammonium, TCA- calcium, TCA-ethadyl, TCA-magnesium, TCA-sodium, TDE, tebuconazole, tebufenozide, tebufenpyrad, tebufloquin, tebupirimfos, tebutam, tebuthiuron, tecloftalam, tecnazene, tecoram, teflubenzuron, tefluthrin, tefuryltrione, tembotrione, temephos, tepa, TEPP, tepraloxydim, terallethrin, terbacil, terbucarb, terbuchlor, terbufos, terbumeton,

terbuthylazine, terbutryn, tetcyclacis, tetrachloroethane, tetrachlorvinphos, tetraconazole, tetradifon, tetrafluron, tetramethrin, tetramethylfluthrin, tetramine, tetranactin, tetrasul, thallium sulfate, thenylchlor, theta-cypermethrin, thiabendazole, thiacloprid, thiadifluor, thiamethoxam, thiapronil, thiazafluron, thiazopyr, thicrofos, thicyofen, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, thifensulfuron-methyl, thifluzamide, thiobencarb, thiocarboxime, thiochlorfenphim, thiocyclam, thiocyclam hydrochloride, thiocyclam oxalate, thiodiazole-copper, thiodicarb, thiofanox, thiofluoximate, thiohempa, thiomersal, thiometon, thionazin, thiophanate, thiophanate-methyl, thioquinox, thiosemicarbazide, thiosultap, thiosultap-diammonium, thiosultap-disodium, thiosultap- monosodium, thiotepa, thiram, thuringiensin, tiadinil, tiaojiean, tiocarbazil, tioclorim, tioxymid, tirpate, tolclofos-methyl, tolfenpyrad, tolylfluanid, tolylmercury acetate, topramezone, tralkoxydim, tralocythrin, tralomethrin, tralopyril, transfluthrin,

transpermethrin, tretamine, triacontanol, triadimefon, triadimenol, triafamone, tri-allate, triamiphos, triapenthenol, triarathene, triarimol, triasulfuron, triazamate, triazbutil, triaziflam, triazophos, triazoxide, tribenuron, tribenuron-methyl, tribufos, tributyltin oxide, tricamba, trichlamide, trichlorfon, trichlormetaphos-3, trichloronat, triclopyr, triclopyr-butotyl, triclopyr-ethyl, triclopyr-triethylammonium, tricyclazole, tridemorph, tridiphane, trietazine, trifenmorph, trifenofos, trifloxystrobin, trifloxysulfuron, trifloxysulfuron-sodium, triflumizole, triflumuron, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop- methyl, trifopsime, triforine, trihydroxytriazine, trimedlure, trimethacarb, trimeturon, trinexapac, trinexapac-ethyl, triprene, tripropindan, triptolide, tritac, triticonazole, tritosulfuron, trunc-call, uniconazole, uniconazole-P, urbacide, uredepa, valerate, validamycin, valifenalate, valone, vamidothion, vangard, vaniliprole, vernolate, vinclozolin, warfarin, warfarin-potassium, warfarin-sodium, xiaochongliulin, xinjunan, xiwojunan, XMC, xylachlor, xylenols, xylylcarb, yishijing, zarilamid, zeatin, zengxiaoan, zeta-cypermethrin, zinc naphthenate, zinc phosphide, zinc thiazole, zineb, ziram, zolaprofos, zoxamide, zuomihuanglong, a-chlorohydrin, a-ecdysone, a-multistriatin, and a-naphthaleneacetic acid.

43. A composition according to claim 1 further comprising an agriculturally acceptable carrier.

44. A composition according to claim 1 wherein said molecule is in the form of a pesticidally acceptable acid addition salt.

45. A composition according to claim 1 wherein said molecule is in the form of a salt derivative.

46. A composition according to claim 1 wherein said molecule is in the form a hydrate.

47. A composition according to claim 1 wherein said molecule is in the form an ester derivative.

48. A composition according to claim 1 wherein said molecule is in the form a crystal polymorph.

49. A composition according to claim 1 wherein said molecule has a ²H in place of ^]H.

50. A composition according to claim 1 wherein said molecule has a ¹⁴C in place of a ¹²C.

51. A composition according to claim 1 further comprising a biopesticide.

52. A composition according to claim 1 further comprising one or more of the following compounds:

(a) 3-(4-chloro-2,6-dimethylphenyl)-4-hydroxy-8-oxa-l-azaspiro[4,5]dec-3-en-2- one;

(b) 3 -(4' -chloro-2,4-dimethyl[ 1 , 1 ' -biphenyl] -3 -yl)-4-hydroxy-8-oxa- 1 - azaspiro[4,5]dec-3-en-2-one;

(c) 4-[[(6-chloro-3-pyridinyl)methyl]methylamino]-2(5H)-furanone;

(d) 4-[[(6-chloro-3-pyridinyl)methyl]cyclopropylamino]-2(5H)-furanone;

(e) 3-chloro-N2-[(15')-l-methyl-2-(methylsulfonyl)ethyl]-Nl-[2-methyl-4- [ 1 ,2,2,2-tetrafluoro- 1 -(trifluoromethyl)ethyl]phenyl]- 1 ,2-benzenedicarboxamide;

(f) 2-cyano-N-ethyl-4-fluoro-3-methoxy-benenesulfonamide;

(g) 2-cyano-N-ethyl-3-methoxy-benzenesulfonamide;

(h) 2-cyano-3-difluoromethoxy-N-ethyl-4-fluoro-benzenesulfonamide;

(i) 2-cyano-3-fluoromethoxy-N-ethyl-benzenesulfonamide;

(j) 2-cyano-6-fluoro-3-methoxy-N,N-dimethyl-benzenesulfonamide;

(k) 2-cyano-N-ethyl-6-fluoro-3-methoxy-N-methyl-benzenesulfonamide;

(1) 2-cyano-3-difluoromethoxy-N,N-dimethylbenzenesulfon-amide;

(m) 3-(difluoromethyl)-N-[2-(3,3-dimethylbutyl)phenyl]-l-methyl-lH-pyrazole-4- carboxamide;

(n) N-ethyl-2,2-dimethylpropionamide-2-(2,6-dichloro-a,a,a-trifluoro-/?-tolyl) hydrazone;

(o) N-ethyl-2,2-dichloro- 1 -methylcyclopropane-carboxamide-2-(2,6-dichloro- α,α,α-trifluoro-p-tolyl) hydrazone nicotine;

(p) 0-{(E-)-[2-(4-chloro-phenyl)-2-cyano-l-(2-trifluoromethylphenyl)-vinyl] } S- methyl thiocarbonate;

(q) (E)-Nl-[(2-chloro-l,3-thiazol-5-ylmethyl)]-N2-cyano-Nl-methylacetamidine; (r) l-(6-chloropyridin-3-ylmethyl)-7-methyl-8-nitro- 1,2,3,5, 6,7-hexahydro- imidazo[l,2-a]pyridin-5-ol;

(s) 4-[4-chlorophenyl-(2-butylidine-hydrazono)methyl)]phenyl mesylate; and (t) N-Ethyl-2,2-dichloro-l-methylcyclopropanecarboxamide-2-(2,6-dichloro- alpha, alpha, a//? za-trifluoro-p-tolyl)hydrazone.

53. A composition according to claim 1 further comprising a compound having one or more of the following modes of action: acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis inhibitor; GABA and glutamate-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acetylcholine receptor agonist; acetylcholine receptor antagonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinic acetylcholine receptor; Midgut membrane disrupter; oxidative phosphorylation disrupter, and ryanodine receptor (RyRs).

54. A composition according to claim 1 further comprising a seed.

55. A composition according to claim 1 further comprising a seed that has been genetically modified to express one or more specialized traits.

56. A composition according to claim 1 wherein said composition is encapsulated inside, or placed on the surface of, a capsule.

57. A composition according to claim 1 wherein said composition is encapsulated inside, or placed on the surface of, a capsule, wherein said capsule has a diameter of about 100-900 nanometers or about 10-900 microns.

58. A process comprising applying a composition according to claim 1 , to an area to control a pest, in an amount sufficient to control such pest.

59. A process according to claim 58 wherein said pest is selected from beetles, earwigs, cockroaches, flies, aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.

60. A process according to claim 58 wherein said pest is from the Phyla Nematoda or Arthropoda.

61. A process according to claim 58 wherein said pest is from the Subphyla Chelicerata, Myriapoda, or Hexapoda.

62. A process according to claim 58 wherein said pest is from the Class of Arachnida, Symphyla, or Insecta.

63. A process according to claim 58 wherein said pest is from the Order Anoplura, Order Coleoptera, Order Dermaptera, Order Blattaria, Order Diptera, Order Hemiptera, Order Hymenoptera, Order Isoptera, Order Lepidoptera, Order Mallophaga, Order Orthoptera, Order Siphonaptera, Order Thysanoptera, Order Thysanura, Order Acarina, or Order Symphyla.

64. A process according to claim 58 wherein said pest is BAW, CEW, or GPA.

65. A process according to claim 58 wherein said amount is from about 0.01 grams per hectare to about 5000 grams per hectare.

66. A process according to claim 58 wherein said amount is from about 0.1 grams per hectare to about 500 grams per hectare.

67. A process according to claim 58 wherein said amount is from about 1 gram per hectare to about 50 grams per hectare.

68. A process according to claim 58 wherein said area is an area where apples, corn, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, or beans, are growing, or the seeds thereof are going to be planted.

69. A process according to claim 58 further comprising applying said composition to a genetically modified plant that has been genetically modified to express one or more specialized traits.

70. A process according to claim 1 where said composition further comprise ammonium sulfate.

71. A process comprising: orally administering; or topically applying; a composition according to claim 1, to a non-human animal, to control endoparasites, ectoparasites, or both. 72. A process comprising applying a composition according to claim 1 to a plant to enhance the plant's health, yield, vigor, quality, or tolerance, at a time when pest activity is low.