HK1083494B

HK1083494B - N-heteroarylnicotinamide derivatives

Info

Publication number: HK1083494B
Application number: HK06103401.1A
Authority: HK
Inventors: 茂三尾; 英史奥井
Original assignee: 三共农业株式会社
Priority date: 2001-11-21
Filing date: 2002-11-19
Publication date: 2009-08-21

Description

N-heteroaryl nicotinamide derivatives

Technical Field

The present invention relates to a specific N-heteroaryl-4- (haloalkyl) nicotinamide derivative, a salt thereof, and a pesticide containing the derivative as an active ingredient.

In addition, the present invention relates to a process for the preparation of the above-mentioned N-heteroaryl-4- (haloalkyl) nicotinamide derivatives and intermediates thereof.

Background

In recent years, commercially available insecticides have been limited in use due to problems such as residue, accumulation, and environmental pollution. Moreover, the use of the same pesticide for a long time causes a problem of the generation of resistant pests. Therefore, it is desired to develop an insecticide having a new molecular structure in consideration of the difference in action from the commercially available insecticides.

In the past, as an N-heteroaryl-4- (trifluoromethyl) nicotinamide derivative, for example, JP-A-10-195072 discloses a compound in which a heteroaryl group is 2-thiazolyl or 1, 3, 4-thiadiazolyl, and a pest control agent containing the compound as an active ingredient. However, these compounds are different from the heteroaryl group of the present invention and their pesticidal effects are insufficient.

Further, 4-trifluoromethylpyridine having a cyano group, a carbamoyl group or a carboxyl group at the 3-position is useful as a raw material for agricultural chemicals or medicines, and can be used as an intermediate for the production of the above-mentioned N-heteroaryl-4- (trifluoromethyl) nicotinamide derivative.

As a method for producing such a production intermediate, there have been known a method described in journal of pharmaceutical chemistry (j.med.chem.), 1967, volume 10, and p.149-154; japanese patent laid-open No. 6-321903; japanese patent laid-open publication No. Hei 7-10841; and Japanese patent laid-open publication No. 2000-38385. Among them, journal of medicinal chemistry (j.med. chem.), 1967, volume 10, and p.149-154 describe production intermediates of lipolysis inhibitors produced by converting a cyano group in 3-cyano-4-trifluoromethylpyridine into a tetrazolyl group. Further, Japanese patent application laid-open No. 6-321903; japanese patent laid-open publication No. Hei 7-10841; and Japanese patent application laid-open No. 2000-38385 disclose that 4-trifluoromethylpyridine having a cyano group or a carbamoyl group at the 3-position is an intermediate for the production of a pest control agent.

However, the above-mentioned method has disadvantages that the number of steps is large and the reaction conditions are severe, and therefore, development of a more industrially advantageous production method has been desired.

Disclosure of Invention

The present inventors have conducted extensive studies on 4- (haloalkyl) nicotinamide derivatives, and as a result, they have found that specific N-heteroaryl-4- (haloalkyl) nicotinamide derivatives have extremely excellent insecticidal activity against various insect pests, and have completed the present invention.

The present inventors have also found that a novel process for producing the above-mentioned N-heteroaryl-4- (haloalkyl) nicotinamide derivative enables a 4-substituted pyridine compound having a cyano group, a carbamoyl group or a carboxyl group at the 3-position, which is an intermediate for the production, to be produced in a high yield, at low cost and in a simple manner, and that the process is industrially advantageous, and thus the present invention has been completed.

The present invention relates to an N-heteroaryl-4- (haloalkyl) nicotinamide derivative represented by the following general formula (I) or a salt thereof, and an agricultural chemical containing the derivative as an active ingredient.

[ wherein R represents C which may be substituted with halogen atom₁～C₆An alkyl group;

R¹represents a hydrogen atom, C which may be substituted₁～C₆Alkyl radical, C₂～C₆An alkenyl or acyl group;

x is represented by the formula C-R²A group represented by (A) or a nitrogen atom;

R²and R³Each independently represents a hydrogen atom, a halogen atom, C which may be substituted by a substituent selected from the following substituent group A₁～C₆Alkyl radical, C₃～C₇Cycloalkyl radical, C₂～C₆Alkenyl radical, C₃～C₇Cycloalkenyl, formyl, substituted by the formula CH ═ NOR⁴(in the formula, R⁴Is a hydrogen atom or C₁～C₆Alkyl), a cyano group, a phenyl group which may be substituted by a substituent selected from the following substituent group B, a 5-or 6-membered heterocyclic group which may be substituted by a substituent selected from the following substituent group B (the heterocyclic group contains 1 to 3 hetero atoms which may be the same or different selected from a nitrogen atom, an oxygen atom and a sulfur atom). Wherein the number of oxygen atoms and sulfur atoms is 0 or 1), C which may be substituted by a substituent selected from the following substituent group A₁～C₆Alkoxy radical, C₁～C₆Alkylthio or phenoxy which may be substituted by a substituent selected from the following substituent group B;

the substituent group A is composed of halogen atom and C₁～C₆Alkoxy radical, C₁～C₆Alkylthio, cyano and phenyl;

substituent group B is C which is substituted by a halogen atom or a substituent selected from the above substituent group A₁～C₆Alkyl, C which may be substituted by a substituent selected from the above substituent group A₁～C₆Alkoxy, cyano and nitro radicals]。

In the present invention, "C₁～C₆The "alkyl group" refers to a linear or branched alkyl group having 1 to 6 carbon atoms, and may be, for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, a 2-methylbutyl group, a 1-methylpentyl group, a neopentyl group, a 1-ethylpropyl group, a hexyl group, a 1-methylpentyl group, a3, 3-dimethylbutyl group, a 2, 2-dimethylbutyl group or a1, 1-dimethylbutyl group, and is preferably a linear or branched alkyl group (C) having 1 to 4 carbon atoms₁～C₄Alkyl group), more preferably an alkyl group having 1 or 2 carbon atoms (C)₁～C₂Alkyl), more preferably methyl.

In the present invention, "halogen atom" means, for example, a fluorine atom, chlorine atom, bromine atom or iodine atom, preferably a fluorine atom, chlorine atom or bromine atom, in R²Among them, a chlorine atom or a bromine atom is more preferable, and among the other substituents, a fluorine atom or a chlorine atom is more preferable, and R is³Among them, a chlorine atom is more preferable, and a fluorine atom is preferable in other substituents.

In the present invention, "C which may be substituted by halogen atom₁～C₆The "alkyl group" means the above-mentioned "C" which may be substituted by 1 to 5 same or different of the above-mentioned "halogen atoms₁～C₆The alkyl group "is preferably a methyl group which may be substituted with 1 to 3 fluorine atoms, and more preferably a trifluoromethyl group.

In the present invention, "C₁～C₆The "alkoxy group" is a linear or branched alkoxy group having 1 to 6 carbon atoms, and may be, for example, a methoxy group, an ethoxy group, an isopropoxy group or a tert-butoxy groupButoxy or hexyloxy, preferably a linear or branched alkoxy group (C) having 1 to 4 carbon atoms₁～C₄Alkoxy group), more preferably a linear or branched alkoxy group (C) having 1 to 3 carbon atoms₁～C₃Alkoxy group), more preferably a linear alkoxy group (C) having 1 or 2 carbon atoms₁～C₂Alkoxy), particularly preferably methoxy.

In the present invention, "C₁～C₆The "alkylthio group" refers to a straight-chain or branched alkylthio group having 1 to 6 carbon atoms, and may be, for example, a methylthio group, an ethylthio group, an isopropylthio group, a tert-butylthio group or an hexylthio group, and is preferably a straight-chain or branched alkylthio group having 1 to 4 carbon atoms (C)₁～C₄Alkylthio group), more preferably a straight-chain or branched alkylthio group (C) having 1 to 3 carbon atoms₁～C₃Alkylthio group), more preferably a linear alkylthio group (C) having 1 or 2 carbon atoms₁～C₂Alkylthio), further preferably methylthio.

In the present invention, "C which may be substituted by a substituent selected from substituent group A₁～C₆The "alkyl group" means a group which may be substituted with the aforementioned "halogen atom", the aforementioned "C₁～C₆Alkoxy group', above-mentioned "C₁～C₆Alkylthio group, cyano group and phenyl group, wherein the "C" is substituted by 1 to 5 substituents which may be the same or different selected from the group consisting of₁～C₆Alkyl radical ", in addition to the above-mentioned" C₁～C₆In addition to alkyl groups ", for example, fluoromethyl, difluoromethyl, trifluoromethyl, pentafluoroethyl, chloromethyl, bromomethyl, iodomethyl, methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, methoxypentyl, methoxyhexyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, isopropoxymethyl, isopropoxyethyl, tert-butoxymethyl, tert-butoxyethyl, hexyloxyhexyl, methylthiomethyl, methylthioethyl, methylthiopropyl, methylthiobutyl, methylthiopentyl, methylthiohexyl, ethylthiomethyl, ethylthiopropyl, isopropylthiomethyl, isopropylthioethyl, tert-butylthioethyl, methylthiohexyl, and the likeMethyl, cyanomethyl, 2-cyanoethyl, 3-cyanopropyl, 4-cyanobutyl, 5-cyanopentyl, 6-cyanohexyl, 1-cyanoethyl, 1-cyanopropyl, 1-cyanoisopropyl or benzyl at R¹In (1), preferably can be represented by the above-mentioned "C₁～C₄Alkoxy group "," C₁～C₄Alkylthio "or cyano-substituted as defined above for" C₁～C₄Alkyl ", more preferably may be represented by the above-mentioned" C "₁～C₂Alkoxy group', above-mentioned "C₁～C₂Alkylthio "or cyano-substituted as defined above for" C₁～C₂Alkyl ", more preferably methyl, methoxymethyl, ethoxymethyl or cyanomethyl, in R²And R³In (b), the above may be preferably represented by "C₁～C₄Alkoxy "substituted by the above" C₁～C₄Alkyl ", more preferably may be represented by the above-mentioned" C "₁～C₃Alkoxy "substituted by the above" C₁～C₃Alkyl group ", more preferably the one which may be substituted by the above-mentioned" C "₁～C₂Alkoxy "substituted by the above" C₁～C₂Alkyl group ", particularly preferably methyl group or methoxymethyl group, most preferably methyl group, and among the other substituents, the above-mentioned" C "which may be substituted by 1 to 3 substituents which may be the same or different selected from the group consisting of fluorine atom and chlorine atom is preferable₁～C₄Alkyl group ", more preferably the above-mentioned" C "which may be substituted with 1 to 3 fluorine atoms₁～C₂Alkyl group "is more preferably methyl group or trifluoromethyl group.

In the present invention, "C₂～C₆The alkenyl group "means a straight-chain or branched alkenyl group having 2 to 6 carbon atoms, and may be, for example, a vinyl group, a 2-chloroethenyl group, a 2-propenyl group, a 2-chloro-2-propenyl group, a3, 3-dichloro-2-propenyl group, a 1-methyl-2-propenyl group, a 2-methyl-2-propenyl group, a 1-butenyl group, a 2-butenyl group, a 3-methyl-2-butenyl group, a 1-pentenyl group, a 2-pentenyl group, a 1-hexenyl group or a 5-hexenyl group, preferably a straight-chain or branched alkenyl group having 2 to 4 carbon atoms (C.sub.₂～C₄Alkenyl), more preferablyIs a linear or branched alkenyl group having 3 or 4 carbon atoms (C)₃～C₄Alkenyl), more preferably 2-propenyl.

In the present invention, examples of the "acyl group" include: an aliphatic acyl group such as an alkylcarbonyl group which may be substituted (the substituent is, for example, a halogen atom or a lower alkoxy group), an unsaturated alkylcarbonyl group, an arylcarbonyl group which may be substituted (the substituent is, for example, a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group, a lower alkoxycarbonyl group or an aryl group), a lower alkoxycarbonyl group which may be substituted (the substituent is, for example, a halogen atom or a tri-lower alkylsilyl group), an alkenyloxycarbonyl group; an aralkyloxycarbonyl group which may be substituted (the substituent may be, for example, a lower alkoxy group or a nitro group), a lower alkanesulfonyl group which may be substituted (the substituent may be, for example, a halogen atom or a lower alkoxy group), an arylsulfonyl group which may be substituted (the substituent may be, for example, a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group, a lower alkoxycarbonyl group or an aryl group), preferably an aliphatic acyl group, more preferably C₂～C₅Alkylcarbonyl group, more preferably acetyl group.

In the present invention, "C₃～C₇The "cycloalkyl group" refers to a cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group or cycloheptyl group which is a cyclic alkyl group having 3 to 7 carbon atoms, preferably a cyclic alkyl group (C) having 3 to 6 carbon atoms₃～C₆Cycloalkyl group), more preferably a cyclic alkyl group (C) having 3 to 5 carbon atoms₃～C₅Cycloalkyl), and cyclopropyl is more preferable.

In the present invention, "C₃～C₇Cycloalkenyl refers to a cyclic alkenyl group having 3 to 7 carbon atoms, and may be, for example, cyclopropenyl, cyclobutenyl or cyclohexenyl, preferably a cyclic alkenyl group having 3 to 6 carbon atoms (C)₃～C₆Cycloalkenyl) and more preferably cyclohexenyl.

In the present invention, "C which may be substituted by a substituent selected from substituent group A₁～C₆Alkoxy "means a radical which may be substituted or unsubstitutedThe above-mentioned "halogen atom", the above-mentioned "C₁～C₆Alkoxy group', above-mentioned "C₁～C₆Alkylthio group, cyano group and phenyl group, wherein the "C" is substituted by 1 to 5 substituents which may be the same or different selected from the group consisting of₁～C₆Alkoxy "in addition to the above" C₁～C₆The alkoxy group "may be, for example, a fluoromethoxy group, difluoromethoxy group, trifluoromethoxy group, pentafluoroethoxy group, chloromethoxy group, bromomethoxy group, iodomethoxy group, methoxymethoxy group, methoxyethoxy group, methoxypropoxy group, methoxybutoxy group, methoxypentyloxy group, methoxyhexyloxy group, ethoxymethoxy group, ethoxyethoxy group, ethoxypropoxy group, isopropoxymethoxy group, isopropoxyethoxy group, tert-butoxymethoxy group, tert-butoxyethoxy group, hexyloxyhexyloxy group, methylthiomethoxy group, methylthioethoxy group, methylthiopropoxy group, methylthiobutoxy group, methylthiopentyloxy group, methylthiohexyloxy group, ethylthiomethoxy group, ethylthioethoxy group, ethylthiopropoxy group, isopropylthiomethoxy group, isopropylthioethoxy group, tert-butylthiomethoxy group, cyanomethoxy group, 2-cyanoethoxy group, chlorothaloethoxy group, iodomethoxy group, 3-cyanopropoxy, 4-cyanobutoxy, 5-cyanopentoxy, 6-cyanohexyloxy, 1-cyanoethoxy, 1-cyanopropoxy, 1-cyanoisopropoxy or benzyloxy, preferably the above-mentioned "C" s which may be substituted by 1 to 3 substituents which may be the same or different and are selected from a fluorine atom and a chlorine atom₁～C₄Alkoxy group ", more preferably the above-mentioned" C "which may be substituted by 1 to 3 fluorine atoms₁～C₂Alkoxy ", more preferably methoxy or trifluoromethoxy.

In the present invention, "phenyl group which may be substituted by a substituent selected from substituent group B" is C which may be substituted by a substituent selected from the above-mentioned "halogen atom", the above-mentioned "substituent selected from substituent group A₁～C₆Alkyl group ", C" which may be substituted by a substituent selected from substituent group A "described above₁～C₆Alkoxy, cyano and nitro, or phenyl substituted with 1 to 5 substituents selected from the group consisting of the same or different substituents R²Preferably, it may be fluorinatedAtom, chlorine atom, optionally substituted "C" described above₁～C₄Alkyl group (the substituent is fluorine atom or chlorine atom), the above-mentioned "C" which may be substituted₁～C₄Alkoxy (the substituent is fluorine atom or chlorine atom), cyano and nitro group, the same or different 1 ~ 3 substituents substituted phenyl, more preferably from fluorine atom, chlorine atom, can be substituted the "C₁～C₃Alkyl group (the substituent is a fluorine atom), the above-mentioned "C" which may be substituted₁～C₂Alkoxy group "(the substituent is a fluorine atom), cyano and nitro group, the same or different 1 ~ 3 substituents substituted phenyl, more preferably phenyl, in other substituents, preferably can be from fluorine atom, chlorine atom, bromine atom, can be substituted the group," C "preferably₁～C₄Alkyl (the substituent is fluorine atom or chlorine atom), the above-mentioned "C₁～C₄Alkoxy, cyano and nitro, or phenyl substituted with 1 to 3 substituents which may be the same or different selected from the group consisting of fluorine atom, chlorine atom, and optionally substituted "C" above₁～C₂Alkyl group (the substituent is fluorine atom), the above-mentioned "C₁～C₂Alkoxy, cyano and nitro, or phenyl substituted with 1 to 3 substituents which may be the same or different selected from the group consisting of alkoxy, cyano and nitro, and phenyl is more preferable.

In the present invention, the "5-or 6-membered heterocyclic group (the heterocyclic group contains 1 to 3 heteroatoms which are the same or different and are selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, wherein the number of oxygen atoms and sulfur atoms is 0 or 1)" may be, for example, a pyridyl group, a pyrimidinyl group, a pyridazinyl group, a pyrazinyl group, a triazolyl group, a furyl group, a thienyl group, a pyrazolyl group, an imidazolyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an isothiazolyl group, a triazolyl group, an oxadiazolyl group or a thiadiazolyl group, preferably a 5-or 6-membered heterocyclic group { 5-or 6-membered heterocyclic group (the heterocyclic group contains 1 to 3 nitrogen atoms) }, more preferably a pyridyl group or a pyrazolyl group.

In the present invention, in the case of the present invention,"5-or 6-membered heterocyclic group which may be substituted by a substituent selected from substituent group B (the heterocyclic group contains 1 to 3 hetero atoms which may be the same or different selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, wherein the number of oxygen atom and sulfur atom is 0 or 1)" is C which may be substituted by the above-mentioned "halogen atom", the above-mentioned "may be substituted by a substituent selected from substituent group A₁～C₆Alkyl group ", C" which may be substituted by a substituent selected from substituent group A "described above₁～C₆The "5-or 6-membered heterocyclic group" substituted with 1 to 4 substituents which may be the same or different selected from the group consisting of alkoxy group ", cyano group and nitro group (the heterocyclic group contains 1 to 3 heteroatoms which may be the same or different selected from the group consisting of nitrogen atom, oxygen atom and sulfur atom, wherein the number of oxygen atom and sulfur atom is 0 or 1)", preferably may be substituted with one or more substituents selected from the group consisting of fluorine atom, chlorine atom and the "C" which may be substituted₁～C₄Alkyl group (the substituent is fluorine atom or chlorine atom), the above-mentioned "C" which may be substituted₁～C₄The "5-or 6-membered heterocyclic group (the heterocyclic group containing 1 to 3 nitrogen atoms)" which may be substituted by 1 to 3 identical or different substituents selected from the group consisting of an alkoxy group (the substituent is a fluorine atom or a chlorine atom), a cyano group and a nitro group, is more preferably a heterocyclic group which may be substituted by a fluorine atom, a chlorine atom and C₁～C₃And a pyridyl group or a pyrazolyl group, which is substituted with 1 to 2 substituents which may be the same or different from each other selected from the group consisting of alkyl groups, and is more preferably a pyridyl group or a pyrazolyl group.

In the present invention, "phenoxy group which may be substituted by a substituent selected from substituent group B" is C which may be substituted by a substituent selected from the above-mentioned "halogen atom", the above-mentioned "substituent selected from substituent group A₁～C₆Alkyl group ", C" which may be substituted by a substituent selected from substituent group A "described above₁～C₆The alkoxy group, cyano group and nitro group are preferably the same or different 1 to 5 substituents substituted phenoxy group, which may be substituted by the above-mentioned "C" which may be substituted by fluorine atom, chlorine atom₁～C₄Alkyl group "(the substituent is fluorine atom or chlorine atom), the above-mentioned optionally substituted“C₁～C₄The alkoxy group (the substituent is fluorine atom or chlorine atom), cyano group and nitro group, the same or different 1-3 substituents substituted phenoxy, more preferably from fluorine atom, chlorine atom, can be substituted the above "C₁～C₃Alkyl group (the substituent is a fluorine atom), the above-mentioned "C" which may be substituted₁～C₂A phenoxy group substituted with 1 to 3 substituents which may be the same or different selected from the group consisting of an alkoxy group (the substituent is a fluorine atom), a cyano group and a nitro group, and more preferably a phenoxy group.

(1) In the present invention, R is preferably trifluoromethyl.

(2) In the present invention, R¹Preferably a hydrogen atom, C which may be substituted₁～C₄Alkyl (substituent is C)₁～C₄Alkoxy radical, C₁～C₄Alkylthio or cyano), C₃～C₄Alkenyl or C₂～C₅Alkylcarbonyl, more preferably a hydrogen atom or C which may be substituted₁～C₂Alkyl (the substituent is C)₁～C₂Alkoxy radical, C₁～C₂Alkylthio group or cyano group), more preferably a hydrogen atom, methyl group, methoxymethyl group, ethoxymethyl group or cyanomethyl group, and particularly preferably a hydrogen atom.

(3) In the present invention, X is preferably represented by the formula C-R²The group shown.

(4) In the present invention, R²Preferably a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, C which may be substituted₁～C₄Alkyl (substituents selected from fluorine atom, chlorine atom, C)₁～C₄Selected from the group consisting of alkoxy and phenyl), C₃～C₆Cycloalkyl radical, C₂～C₄Alkenyl radical, C₃～C₆Cycloalkenyl group, phenyl group which may be substituted { substituent selected from fluorine atom, chlorine atom, C which may be substituted₁～C₄Alkyl (the substituent is fluorine atom or chlorine atom), C which may be substituted₁～C₄An alkoxy group (the substituent is fluorine atom or chlorine atom), a cyano group, and a nitro group, or a 5-or 6-membered heterocyclic group which may be substituted { the heterocyclic group contains 1 to 3 nitrogen atoms; the substituents being selected from fluorine atoms, chlorine atoms, optionally substituted C₁～C₄Alkyl (the substituent is fluorine atom or chlorine atom), C which may be substituted₁～C₄Alkoxy (the substituent is fluorine atom or chlorine atom), cyano, nitro, or C which may be substituted₁～C₄Alkoxy (substituents selected from fluorine atom, chlorine atom, C)₁～C₄Selected from the group consisting of alkoxy and phenyl), C₁～C₄Alkylthio group or optionally substituted phenoxy { substituent selected from fluorine atom, chlorine atom, C which may be substituted₁～C₄Alkyl (the substituent is fluorine atom or chlorine atom), C which may be substituted₁～C₄Alkoxy (the substituent is fluorine atom or chlorine atom), cyano group and nitro group, more preferably hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, C which may be substituted₁～C₃Alkyl (the substituent is C)₁～C₃Alkoxy group), C₃～C₅Cycloalkyl radical, C₃～C₄Alkenyl, optionally substituted phenyl (substituents selected from fluorine atom, chlorine atom, C optionally substituted by fluorine atom₁～C₃Alkyl, C which may be substituted by fluorine atoms₁～C₃Alkoxy group, cyano group and nitro group), optionally substituted pyridyl group (the substituent is selected from the group consisting of fluorine atom, chlorine atom and C₁～C₃A substituent selected from the group consisting of alkyl groups), pyrazolyl which may be substituted (the substituent is selected from the group consisting of a fluorine atom, a chlorine atom and C₁～C₃Selected from the group consisting of alkyl groups), C which may be substituted by fluorine atoms₁～C₃Alkoxy radical, C₁～C₃Alkylthio or substituted phenoxy (substituents selected from fluorine atom, chlorine atom, C which may be substituted by fluorine atom₁～C₃Alkyl, C which may be substituted by fluorine atoms₁～C₃Selected from the group consisting of alkoxy groups, cyano groups and nitro groups), more preferably a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, C₁～C₃Alkyl, cyclopropyl, allyl, phenyl, pyridyl, pyrazolyl, C₁～C₂Alkoxy radical, C₁～C₂Alkylthio or phenoxy, particularly preferably hydrogen atom, chlorine atom, bromine atom, methyl, ethyl or methoxy.

(5) In the present invention, R³Preferably a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, C which may be substituted₁～C₄Alkyl (the substituent is C)₁～C₄Alkoxy group), C₃～C₆Cycloalkyl, formyl, or a compound of formula CH ═ NOR^4a(in the formula, R^4aIs a hydrogen atom or C₁～C₄Alkyl), cyano, or phenyl which may be substituted { the substituent is selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, C which may be substituted₁～C₄Alkyl (the substituent is fluorine atom or chlorine atom), C₁～C₄Alkoxy, cyano and nitro, more preferably 1 to 3 substituents selected from the group consisting of hydrogen atom, fluorine atom, chlorine atom, and optionally substituted C₁～C₂Alkyl (substituent is C)₁～C₂Alkoxy group), C₃～C₅Cycloalkyl or phenyl which may be substituted { the substituent is selected from the group consisting of a fluorine atom, a chlorine atom, C which may be substituted₁～C₂Alkyl (the substituent is fluorine atom), C₁～C₂1 to 3 identical or different substituents selected from the group consisting of alkoxy, cyano and nitro }, more preferably a hydrogen atom, a chlorine atom, a methyl group, a methoxymethyl group, a cyclopropyl group or a phenyl group, and particularly preferably a hydrogen atom or a methyl group.

The 4- (haloalkyl) nicotinamide derivative of the invention is preferably a compound in which,

(A1) r is a trifluoromethyl group, and R is a trifluoromethyl group,

(A2)R¹is a hydrogen atom, C which may be substituted₁～C₄Alkyl (substituent is C)₁～C₄Alkoxy radical, C₁～C₄Alkylthio or cyano), C₃～C₄Alkenyl or C₂～C₅An alkyl-carbonyl group, a carboxyl group,

(A3) x is of the formula C-R²The group of the formula (I) is,

(A4)R²is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, C which may be substituted₁～C₄Alkyl (substituents selected from fluorine atom, chlorine atom, C)₁～C₄Selected from the group consisting of alkoxy and phenyl), C₃～C₆Cycloalkyl radical, C₂～C₄Alkenyl radical, C₃～C₆Cycloalkenyl group, phenyl group which may be substituted { substituent selected from fluorine atom, chlorine atom, C which may be substituted₁～C₄Alkyl (the substituent is fluorine atom or chlorine atom), C which may be substituted₁～C₄An alkoxy group (the substituent is fluorine atom or chlorine atom), a cyano group, and a nitro group, or a 5-or 6-membered heterocyclic group which may be substituted { the heterocyclic group contains 1 to 3 nitrogen atoms; the substituents being selected from fluorine atoms, chlorine atoms, optionally substituted C₁～C₄Alkyl (the substituent is fluorine atom or chlorine atom), C which may be substituted₁～C₄Alkoxy (the substituent is fluorine atom or chlorine atom), cyano, nitro, or C which may be substituted₁～C₄Alkoxy (substituents selected from fluorine atom, chlorine atom, C)₁～C₄Selected from the group consisting of alkoxy and phenyl), C₁～C₄Alkylthio group or optionally substituted phenoxy { substituent selected from fluorine atom, chlorine atom, C which may be substituted₁～C₄Alkyl (the substituent is fluorine atom or chlorine atom), C which may be substituted₁～C₄Alkoxy (the substituent is fluorine atom or chlorine atom), cyano, and nitro },

(A5)R³is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, C which may be substituted₁～C₄Alkyl (substituent is C)₁～C₄Alkoxy group), C₃～C₆Cycloalkyl, formyl, or a compound of formula CH ═ NOR^4a(in the formula, R^4aIs a hydrogen atom or C₁～C₄Alkyl), cyano, or phenyl which may be substituted { the substituent is selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, and C which may be substituted₁～C₄Alkyl (the substituent is fluorine atom or chlorine atom), C₁～C₄1 to 3 identical or different substituents selected from the group consisting of alkoxy, cyano and nitro };

more preferably a compound wherein,

(b1) r is a trifluoromethyl group, and R is a trifluoromethyl group,

(b2)R¹is a hydrogen atom or C which may be substituted₁～C₂Alkyl (the substituent is C)₁～C₂Alkoxy radical, C₁～C₂Alkylthio or cyano),

(b3) x is of the formula C-R²The group of the formula (I) is,

(b4)R²is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, C which may be substituted₁～C₃Alkyl (the substituent is C)₁～C₃Alkoxy group), C₃～C₅Cycloalkyl radical, C₃～C₄Alkenyl, optionally substituted phenyl (substituents selected from fluorine atom, chlorine atom, C optionally substituted by fluorine atom₁～C₃Alkyl, C which may be substituted by fluorine atoms₁～C₃Alkoxy group, cyano group and nitro group), optionally substituted pyridyl group (the substituent is selected from the group consisting of fluorine atom, chlorine atom and C₁～C₃A substituent selected from the group consisting of an alkyl group), a pyrazolyl group which may be substituted (the substituent is selected from the group consisting of a fluorine atom, a chlorine atom and C₁～C₃A substituent selected from the group consisting of alkyl groups), C which may be substituted with a fluorine atom₁～C₃Alkoxy radical, C₁～C₃Alkylthio or substituted phenoxy (substituents selected from fluorine atom, chlorine atom, C which may be substituted by fluorine atom₁～C₃Alkyl, C which may be substituted by fluorine atoms₁～C₃Alkoxy, cyano and nitro),

(b5)R³is a hydrogen atom, a fluorine atom, a chlorine atom, C which may be substituted₁～C₂Alkyl (the substituent is C)₁～C₂Alkoxy group), C₃～C₅Cycloalkyl or phenyl which may be substituted { the substituent is selected from the group consisting of a fluorine atom, a chlorine atom, C which may be substituted₁～C₂Alkyl (the substituent is fluorine atom), C₁～C₂1 to 3 identical or different substituents selected from the group consisting of alkoxy, cyano and nitro };

further preferred is a compound in which,

(C1) r is a trifluoromethyl group, and R is a trifluoromethyl group,

(C2)R¹is a hydrogen atom, a methyl group, a methoxymethyl group, an ethoxymethyl group or a cyanomethyl group,

(C3) x is of the formula C-R²The group of the formula (I) is,

(C4)R²is hydrogen atom, fluorine atom, chlorine atom, bromine atom, C₁～C₃Alkyl, cyclopropyl, allyl, phenyl, pyridyl, pyrazolyl, C₁～C₂Alkoxy radical, C₁～C₂An alkylthio group or a phenoxy group, or a substituted or unsubstituted alkylthio group,

(C5)R³is hydrogen atom, chlorine atom, methyl, methoxymethyl, cyclopropyl or phenyl;

particularly preferred is a compound in which,

(D1) r is a trifluoromethyl group, and R is a trifluoromethyl group,

(D2)R¹is a hydrogen atom, and is a hydrogen atom,

(D3) x is of the formula C-R²The group of the formula (I) is,

(D4)R²is hydrogen atom, chlorine atom, bromine atom, methyl, ethyl or methoxy,

(D5)R³is a hydrogen atom or a methyl group;

most preferably

(e) N- (5-isoxazolyl) -4- (trifluoromethyl) nicotinamide,

N- (3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide,

N- (4-chloro-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide,

N- (4-bromo-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide,

N- (4-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide,

N- (4-ethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide, or

N- (4-methoxy-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide.

The N-heteroaryl-4- (haloalkyl) nicotinamide derivative of the invention can form a salt together with an acidic substance or a basic substance, for example, an alkali metal salt, an alkaline earth metal salt, or an ammonium salt in the case of having a proton dissociative in the molecule, or a salt with an acidic substance, for example, a sulfate, a hydrochloride, a nitrate, a phosphate, or the like. These salts are included in the present invention as long as they are used as an agricultural or horticultural insecticide.

In the present invention, the "alkali metal salt" may be, for example, a sodium salt, a potassium salt or a lithium salt, preferably a sodium salt or a potassium salt.

In the present invention, the "alkaline earth metal salt" may be, for example, a calcium salt or a magnesium salt, preferably a calcium salt.

Solvates (preferably hydrates) of the N-heteroaryl-4- (haloalkyl) nicotinamide derivatives of the invention are also encompassed by the invention.

The N-heteroaryl-4- (haloalkyl) nicotinamide derivatives of the invention may also be compounds having asymmetric carbon atoms, in which case the invention encompasses a mixture of one optically active form and several optically active forms in any desired ratio.

Representative compounds of the present invention are listed in tables 1 and 2 below, but the present invention is not limited to these compounds.

In the following tables, "Me" represents a methyl group, "Et" represents an ethyl group, "Pr" represents a propyl group, "iPr" represents an isopropyl group, "cPr" represents a cyclopropyl group, "Bu" represents a butyl group, "Pent" represents a pentyl group, "Hex" represents a hexyl group, "Ph" represents a phenyl group, and "4-CF₃-Ph "represents 4-trifluoromethylphenyl group," CHO "represents formyl group," Ac "represents acetyl group," 4-CF₃-Py-3-y1 "represents 4-trifluoromethyl-3-pyridyl," iBu "represents isobutyl," cBu "represents cyclobutyl," cPent "represents cyclopentyl," cHex-1-en-1-y1 "represents 1-cyclohexenyl, and" 1-Pyza "represents 1-pyrazolyl.

(Table 1)

(Table 2)

Among the above exemplified compounds, preferred compounds are those of compound Nos. 1-1, 1-2, 1-3, 1-5, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-25, 1-36, 1-37, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-47, 1-49, 1-51, 1-53, 1-55, 1-56, 1-57, 1-58, 1-59, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 1-68, 1-69, 1-70, 1-71, 1-60, 1-61, 1-62, 1-63, 1-64, 1-65, 1-66, 1-67, 1-68, 1-69, 1-70, 1-72, 1-73, 1-74, 1-75, 1-76, 1-77, 1-78, 1-79, 1-80, 1-81, 1-82, 1-83, 1-84, 1-85, 1-86, 1-87, 1-88, 1-89, 1-90, 1-91, 1-92, 1-93, 1-94, 1-95 and 2-2, more preferably compound numbers 1-1, 1-2, 1-20, 1-21, 1-37, 1-38, 1-39, 1-40, 1-41, 1-42, 1-43, 1-53, 1-57, 1-60, 1-61, 1-62, 1-64, 1-65, 1-66, 1-67, 1-68, 1-69, 1-70, 1-71, 1-77, 1-78, 1-79, 1-80, 1-81, 1-82, 1-86, 1-89, 1-90, 1-92, 1-93, 1-94 and 2-2, more preferably the compounds of compound Nos. 1-1, 1-2, 1-20, 1-21, 1-38, 1-39, 1-40, 1-42, 1-62, 1-64, 1-65, 1-67, 1-77, 1-93 and 1-94, particularly preferably the compounds of compound Nos. 1-1, 1-2, 1-69, 1-70, 1-71, 1-77, 1-80, 1-81, 1-82, 1-20, 1-40, 1-62, 1-64, and 1-77.

In addition, the present invention relates to a process for the preparation of a compound of the formula (I)

[ in the formula, R, X, R¹And R³Denotes the same definition as above]

A process for producing an N-heteroaryl-4- (haloalkyl) nicotinamide derivative represented by the general formula (VII)

[ wherein R represents the same definition as above,

a represents cyano, carbamoyl or carboxyl group ]

A nitrile compound represented by the formula (I) or a salt thereof,

wherein, is represented by the general formula (IV)

[ wherein R represents the same definition as above ]

An amine compound represented by the general formula (V)

X^a-CH＝CH-CN (V)

[ in the formula, X^aRepresents a leaving group]

An acrylonitrile compound represented by the general formula (VI)

(R^aO)₂CH-CH₂-CN (VI)

[ in the formula, R^aRepresents a hydrogen atom or C₁～C₆Alkyl radical]

Reaction of a propionitrile compound represented by the general formula (II)

[ wherein R represents the same definition as above ]

A nitrile compound represented by the general formula (VII) or a salt thereof, and a base is added to the nitrile compound or the salt thereof

[ wherein R represents the same definition as above and A represents a cyano group, a carbamoyl group or a carboxyl group ]

The 4-substituted pyridine compound having a cyano group, a carbamoyl group or a carboxyl group at the 3-position represented by (VIII), can be prepared by adding an acid or a base to the 4-substituted pyridine compound and hydrolyzing it, if necessary

[ wherein R represents the same definition as above ]

A carboxylic acid compound represented by the general formula (IX) and a halogenating agent

[ wherein R represents the same definition as above, and X^bRepresents a chlorine atom or a bromine atom]

An acid halide compound represented by the formula (III), and then reacting the acid halide compound with a compound represented by the formula (III)

[ in the formula, R, X, R¹And R³Denotes the same definition as above]

The amino compound represented by (a) can be prepared by reacting and, if necessary, further alkylating, alkenylating or acylating the amino compound.

In the present invention, the "leaving group" is not particularly limited as long as it is a functional group having a releasing ability, and may be, for example, a halogen atom or C₁～C₆Alkoxy, phenoxy or cyano, preferably a chlorine atom, methoxy or ethoxy, more preferably methoxy.

In the present invention, R^aThe alkyl group is preferably a linear or branched alkyl group having 1 to 3 carbon atoms, more preferably a methyl group or an ethyl group, and still more preferably a methyl group.

The compound (II) of the present invention can be prepared, for example, as an alkali metal salt, an alkaline earth metal salt or an ammonium salt.

Solvates (preferably hydrates) of the compounds (II) of the invention are also encompassed by the invention.

In the present invention, optical isomers often exist in each of the compound (II), the compound (IV), the compound (V), the compound (VI), the compound (VII), the compound (VIII) and the compound (IX), and each of the compounds of the present invention includes one optically active form and a mixture of several optically active forms mixed in an arbitrary ratio.

In the production method of the present invention, the compound (IV) can be produced by using commercially available products or according to a known method (for example, the methods described in Tetrahedron Letters, 1989, 30, 6173-6176, U.S. Pat. No. U S2198260, Arch. pharm., 1984, 317, 156-162 or Su Union's Committee of sciences, communications, chemical section (Izv. Akad. Nauk. SSSR. Ser. Khim.), 1955, 179).

In the production method of the present invention, the compound (V) can be produced by a commercially available method or a publicly known method (for example, in the case where X is an alkoxy group, according to the method described in journal of American chemical society (J.Am.chem, Soc.), 1947, 69, 2660 or journal of Industrial chemistry (day), 1970, 73, 1013, in the case where X is a chlorine atom, according to the method described in journal of organic chemistry (J.org.chem.), 1964, 29, 1800-1808, journal of organic chemistry (J.org.chem.), 1970, 35, 2133 or Collect.Czech.chem.Commun., 1983, 48, 89-95).

In the production process of the present invention, a commercially available compound (VI) may be used, or a known method (for example, R) may be used¹In the case of butoxy, preparation was carried out according to the method described in j.chem.soc.chem.commun., 1977, 333).

The N-heteroaryl-4- (haloalkyl) nicotinamide derivative of the invention can be prepared according to the following steps a to C.

(Process A)

In the above formula, R, R¹X and R³The same definitions as those described above are indicated,

y represents a hydroxyl group or a halogen atom (preferably a chlorine atom),

z represents a leaving group (preferably a halogen atom such as chlorine, bromine or iodine; trihalomethoxy such as trichloromethoxy; lower alkanesulfonyloxy such as methanesulfonyloxy or ethanesulfonyloxy; halogenated lower alkanesulfonyloxy such as trifluoromethanesulfonyloxy or pentafluoroethanesulfonyloxy; or arylsulfonyloxy such as benzenesulfonyloxy, p-toluenesulfonyloxy or p-nitrobenzenesulfonyloxy).

(Process A-1)

The step A-1 is a step of reacting a 4- (haloalkyl) pyridine-3-carboxylic acid represented by the general formula (X) or an acid halide thereof with an amine compound represented by the general formula (IIIa) or a salt thereof to prepare the compound (Ia) of the present invention.

(I) In the case where Y in the compound (X) is a hydroxyl group, this step is a step of reacting the compound (X) with the compound (IIIa) in an inert solvent in the presence of a base and a condensing agent to prepare the compound (Ia).

In the present step, the base to be used is not particularly limited as long as it is a base having a normal pH of 8 or more, and may be, for example, a hydroxide of an alkali metal such as sodium hydroxide or potassium hydroxide; hydroxides of alkaline earth metals such as calcium hydroxide and magnesium hydroxide; carbonates of alkali metals such as sodium carbonate and potassium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; metal hydrides such as sodium hydride and potassium hydride; alkoxides such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; organic bases such as triethylamine, N-dimethylaniline and pyridine; alternatively, organic metals such as methyllithium, butyllithium, methylmagnesium bromide, lithium diisopropylamide, and the like are preferable, alkali metal carbonates, alkali metal bicarbonates, or organic bases are preferable, and sodium carbonate, potassium carbonate, pyridine, or triethylamine is more preferable.

The amount of the base used is usually 1.0 to 10.0mol, preferably 1.0 to 5.0mol, based on 1mol of the compound (X).

The condensing agent to be used is not particularly limited as long as it is a reagent having a condensing ability, and may be, for example, chloroformic acid C such as methyl chloroformate and ethyl chloroformate₁～C₄Pyridine salts such as alkyl esters and 2-chloro-1-methylpyridine iodide; and carbodiimides such as dicyclohexylcarbodiimide, preferably pyridinium salts, and more preferably 2-chloro-1-methyl iodideA pyridine.

The amount of the condensing agent to be used is usually 1.0 to 5.0mol, preferably 1.0 to 2.0mol, based on 1mol of the compound (X).

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to a certain extent, and examples thereof include ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran and dioxane; aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene; nitriles such as acetonitrile; amides such as N, N-dimethylformamide, N-dimethylacetamide and N-methyl-2-pyrrolidone; sulfoxides such as dimethyl sulfoxide and sulfolane; halogenated hydrocarbons such as methylene chloride and chloroform; esters such as ethyl acetate and ethyl propionate; aliphatic hydrocarbons such as hexane, cyclohexane and heptane; pyridines such as pyridine and picoline; alternatively, the mixed solvent is preferably an ether, a halogenated hydrocarbon, an ester, an aliphatic hydrocarbon or an aromatic hydrocarbon, and more preferably tetrahydrofuran, dichloromethane, ethyl acetate or toluene.

The amount of the solvent used is usually 1.0 to 20 liters, preferably 1.0 to 10 liters, based on 1mol of the compound (X).

The reaction temperature varies depending on the raw material compound, the reaction reagent, the solvent and the like, and is usually-40 ℃ to 150 ℃, preferably 0 ℃ to 100 ℃.

The reaction time varies depending on the raw material compound, the reaction reagent, the solvent, the reaction temperature, and the like, and is usually 6 minutes to 48 hours, preferably 10 minutes to 24 hours.

(II) when Y in the compound (X) is a halogen atom, this step is a step of reacting the compound (X) with the compound (IIIa) in an inert solvent in the presence of a base to prepare a compound (Ia).

The base to be used is not particularly limited as long as it is usually at a pH of 8 or higher, and examples thereof include hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide; hydroxides of alkaline earth metals such as calcium hydroxide and magnesium hydroxide; carbonates of alkali metals such as sodium carbonate and potassium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; metal hydrides such as sodium hydride and potassium hydride; alkoxides such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; organic bases such as triethylamine, N-dimethylaniline and pyridine; alternatively, organic metals such as methyllithium, butyllithium, methylmagnesium bromide, lithium diisopropylamide, and the like are preferable, alkali metal carbonates, alkali metal bicarbonates, or organic bases are preferable, and sodium carbonate, sodium bicarbonate, pyridine, or triethylamine is more preferable.

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to a certain extent, and examples thereof include ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran and dioxane; aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene; nitriles such as acetonitrile; amides such as N, N-dimethylformamide, N-dimethylacetamide and N-methyl-2-pyrrolidone; sulfoxides such as dimethyl sulfoxide and sulfolane; halogenated hydrocarbons such as methylene chloride and chloroform; esters such as ethyl acetate and ethyl propionate; aliphatic hydrocarbons such as hexane, cyclohexane and heptane; pyridines such as pyridine and picoline; alternatively, the mixed solvent is preferably an ether, a halogenated hydrocarbon, an ester, an aliphatic hydrocarbon or an aromatic hydrocarbon, and more preferably tetrahydrofuran, ethyl acetate or toluene. In addition, in this step, the reaction of the 2-layer system may be carried out using the water-insoluble solvent and water.

The amount of the solvent used is usually 1.0 to 20 liters, preferably 1.0 to 10 liters, based on 1mol of the compound (IIIa).

The reaction temperature varies depending on the raw material compound, the reaction reagent, the solvent and the like, and is usually-40 ℃ to the reflux temperature of the reaction system, preferably 0 ℃ to 100 ℃.

The compound (X) used in the present step may be a commercially available carboxylic acid, or may be produced by a method of converting the carboxylic acid into an acid halide according to a conventional method or a method described later.

The amine compound (IIIa) used in the present step may be a commercially available compound or may be prepared by a known method. For example, the 5-aminoisoxazole derivative can be prepared according to a known method, for example, the method described in Bull. chem.Soc.Jpn., 1968, Vol.41, p.267, chem. pharm. Bull., 1966, Vol.14, 1277-cake 1286, Heterocycles, 1991, Vol.32, 1153-cake 1158, J.chem.Soc.Perkin Trans I, 1984, 1079-cake 1083, or J.hetrocycl.chem.1986, Vol.23, 1535-cake 1538. The 4-amino- [1, 2, 4] oxadiazole derivative can be produced according to a known method, for example, a method described in journal of organic chemistry (J.org.chem.), 1963, Vol.28, 1816. sup. 1821, J.Prakt.chem., 1971, 313, 1065. sup. 1069, U.S. Pat. No. 3,3917632, or Wutian institute (Japan), 1971, 30, 475. sup. 492.

(Process A-2)

The step A-2 is a step of reacting the compound (Ia) prepared in the step A-1 with a compound represented by the general formula (XI) in an inert solvent in the presence of a base to prepare a compound (Ib) of the present invention.

The amount of the compound (XI) used in the present step is usually 1.0 to 20.0mol, preferably 1.0 to 10.0mol, based on 1mol of the compound (Ia).

The base used in the present step is not particularly limited as long as it is a base having a pH of usually 8 or higher, and may be, for example, a hydroxide of an alkali metal such as sodium hydroxide or potassium hydroxide; hydroxides of alkaline earth metals such as calcium hydroxide and magnesium hydroxide; carbonates of alkali metals such as sodium carbonate and potassium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; metal hydrides such as sodium hydride and potassium hydride; alkoxides such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; alternatively, organic bases such as triethylamine, N-dimethylaniline and pyridine are preferably alkali metal carbonates, alkali metal bicarbonates, alkali metal hydrides or organic salts, and more preferably sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate or sodium hydride.

The amount of the base used is usually 1.0 to 20.0mol, preferably 1.0 to 10.0mol, based on 1mol of the compound (Ia).

The amount of the solvent used is usually 1.0 to 20 liters, and preferably 1.0 to 10 liters, based on 1mol of the compound (Ia).

The reaction temperature varies depending on the raw material compound, the reaction reagent, the solvent, etc., and is usually-40 ℃ to the reflux temperature of the reaction system, preferably 0 to 100 ℃.

(Process B)

In the above formula, R, R¹And R³Represents the same definition as above, R^2aRepresents a halogen atom.

Step B is a step of reacting a 5-isoxazolyl-4- (haloalkyl) nicotinamide derivative represented by general formula (Ic) with a halogenating agent in an inert solvent to prepare a 5- (4-haloisoxazolyl) -4- (haloalkyl) nicotinamide derivative (Id) when X is a CH group in compound (I).

The halogenating agent used in the present step is not particularly limited as long as it is a compound generally used in halogenation reactions, and may be, for example, molecular halogen such as chlorine, bromine, iodine, etc.; sulfonyl chlorides such as sulfonyl chloride; halogenating agents having a halogen atom at a nitrogen atom, such as N-chlorosuccinimide, N-bromosuccinimide, trichlorocyanuric acid, and 1, 3-dichloro-5, 5-dimethylhydantoin; alternatively, the oxide of a chlorine atom such as sodium chlorite, sodium hypochlorite, or tert-butylhypochlorite is preferably chlorine, bromine, sodium hypochlorite, sulfuryl chloride, or N-chlorosuccinimide.

The amount of the halogenating agent used in this step is usually 1.0 to 10.0mol, preferably 1.0 to 5.0mol, based on 1mol of the compound (Ic).

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to a certain extent, and examples thereof include ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran and dioxane; aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene; nitriles such as acetonitrile; amides such as N, N-dimethylformamide, N-dimethylacetamide and N-methyl-2-pyrrolidone; sulfoxides such as dimethyl sulfoxide and sulfolane; halogenated hydrocarbons such as methylene chloride and chloroform; esters such as ethyl acetate and ethyl propionate; aliphatic hydrocarbons such as hexane, cyclohexane and heptane; pyridines such as pyridine and picoline; alternatively, the mixed solvent is preferably an ester or a halogenated hydrocarbon, and more preferably dichloroethane or ethyl acetate.

The amount of the solvent used is usually 1.0 to 20 liters, preferably 1.0 to 10 liters, based on 1mol of the compound (Ic).

The reaction temperature varies depending on the raw material compound, the reaction reagent, the solvent, etc., and is usually-40 to 150 ℃ and preferably 0 to 100 ℃.

(Process C)

In the above formula, R, R¹X and R⁴The same definitions as above are indicated.

In the process C, R is in the compound (I)³In the case of a formyl group, a step of reacting a 5-isoxazolyl-4- (haloalkyl) nicotinamide derivative represented by the general formula (Ie) with a hydroxylamine compound represented by the general formula (XII), a hydrate thereof, or a salt thereof to prepare an oxime compound represented by the general formula (If) of the present invention.

The amount of the compound (XII) used in the present step is usually 1.0 to 20.0mol, preferably 1.0 to 10mol, based on the compound (Ie).

This step may be carried out in the presence or absence of a solvent.

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to a certain extent, and examples thereof include alcohols such as methanol, ethanol, and ethylene glycol; ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, and dioxane; aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene; nitriles such as acetonitrile; amides such as N, N-dimethylformamide, N-dimethylacetamide and N-methyl-2-pyrrolidone; sulfoxides such as dimethyl sulfoxide and sulfolane; halogenated hydrocarbons such as methylene chloride and chloroform; esters such as ethyl acetate and ethyl propionate; aliphatic hydrocarbons such as hexane and cyclohexane; pyridines such as pyridine and picoline; aliphatic carboxylic acids such as acetic acid; water; alternatively, the mixed solvent is preferably an alcohol or an ether, and more preferably methanol or ethanol.

The amount of the solvent used is usually 0.1 to 20.0 liters, preferably 1 to 10.0 liters, based on 1mol of the compound (Ie).

This step may be carried out in the presence or absence of an acid.

The acid to be used is not particularly limited as long as it is an acid having a normal pH of 6 or less, and examples thereof include inorganic acids such as hydrochloric acid, sulfuric acid, perchloric acid, and nitric acid; carboxylic acids such as formic acid, acetic acid and propionic acid; sulfonic acids such as methanesulfonic acid and benzenesulfonic acid; the acid adduct of an amine such as a p-toluenesulfonate of pyridine is preferably a carboxylic acid or a sulfonic acid.

The amount of the acid used is usually 0.01 to 100mol, preferably 0.01 to 30mol, based on 1mol of the compound (Ie).

The reaction temperature varies depending on the raw material compound, the reaction reagent, the solvent and the like, and is usually from-10 ℃ to the reflux temperature of the reaction system, preferably from room temperature to the reflux temperature of the reaction system.

The reaction time varies depending on the reaction temperature, the raw material compound, the reaction reagent, etc., and is usually 30 minutes to 48 hours, preferably 1 to 24 hours.

After the completion of the above reaction steps, the target compound in each step can be recovered from the reaction mixture by a conventional method. For example, it can be obtained by suitably neutralizing the reaction mixture or, in the case where insoluble matter is present, removing it by filtration, adding a water-immiscible organic solvent, washing with water, and then distilling off the solvent. The target compound obtained can be purified as necessary by a conventional method such as recrystallization, reprecipitation or chromatography. The target compound in each step may be used in the subsequent reaction without purification.

In the case of the N-heteroaryl-4- (haloalkyl) nicotinamide derivatives of the invention as the acid component of the salt, the salt can be prepared, for example, by mixing the N-heteroaryl-4- (haloalkyl) nicotinamide derivative with a base in the presence or absence of a solvent, and then distilling off the solvent.

The base to be used is not particularly limited as long as it is usually at a pH of 8 or higher, and may be, for example, an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide; alkali metal carbonates such as sodium carbonate, potassium carbonate, and cesium carbonate; metal alkoxides such as sodium methoxide, sodium ethoxide, and potassium tert-butoxide; alkali metal salts of organic acids such as sodium acetate, potassium acetate, sodium formate and potassium formate; alkali metal hydrides such as sodium hydride and potassium hydride; alkali metals such as sodium and potassium; aliphatic tertiary amines such as triethylamine, tributylamine, and diisopropylethylamine; aliphatic cyclic tertiary amines such as 1, 4-diazabicyclo [2.2.2] octane (DABCO) and 1, 8-diazabicyclo [5.4.0] undec-7-ene (DBU); pyridines such as pyridine, collidine and 4- (N, N-dimethylamino) pyridine; metal amide compounds such as lithium amide and sodium amide; or an organic metal base such as butyl lithium, sec-butyl lithium, lithium diisopropylamide, sodium bis (trimethylsilyl) amide, or lithium bis (trimethylsilyl) amide.

The solvent to be used is not particularly limited as long as it is a solvent which does not inhibit the reaction and dissolves the starting material to some extent, and may be, for example, water; alcohols such as methanol, ethanol and tert-butanol; ketones such as acetone and methyl isobutyl ketone; nitriles such as acetonitrile; esters such as ethyl acetate; halogenated hydrocarbons such as dichloromethane, chloroform, dichloroethane and the like; ethers such as diethyl ether, tetrahydrofuran, and dioxane; aromatic hydrocarbons such as toluene; amides such as dimethylformamide and dimethylacetamide; sulfoxides such as dimethyl sulfoxide, etc.; or a mixed solvent thereof.

In the case where the N-heteroaryl-4- (haloalkyl) nicotinamide derivative of the present invention is used as a base component of a salt, the salt can be prepared, for example, by mixing the N-heteroaryl-4- (haloalkyl) nicotinamide derivative with an acid in the presence or absence of a solvent, and then distilling off the solvent.

The acid to be used is not particularly limited as long as it is an acid having a normal pH of 6 or less, and may be, for example, an inorganic acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, or phosphoric acid; or organic acids such as formic acid, acetic acid, toluenesulfonic acid, oxalic acid, benzoic acid, and the like.

The compound (X) as a starting material in the step a can be prepared according to the steps D to H described below.

(Process D)

In the formula, R and X^aThe same definitions as above are indicated.

This step is a step of reacting compound (IV) with compound (V) in an inert solvent or in the absence of a solvent in the presence of a base or an acid to prepare compound (II).

The amount of the compound (V) used in the present step is usually 1.0 to 10.0mol, preferably 1.0 to 5mol, based on 1mol of the compound (IV).

When a base is used in this step, the base to be used is not particularly limited as long as it is usually at a pH of 8 or more, and may be, for example, a hydroxide of an alkali metal such as sodium hydroxide or potassium hydroxide; hydroxides of alkaline earth metals such as calcium hydroxide and magnesium hydroxide; carbonates of alkali metals such as sodium carbonate and potassium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; alkali metals such as sodium and potassium; metal hydrides such as sodium hydride and potassium hydride; alkoxides such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; organic bases such as triethylamine, N-dimethylaniline and pyridine; or organic metals such as methyllithium, butyllithium, methylmagnesium bromide, lithium diisopropylamide, etc., preferably alkali metal hydroxides; metal hydrides or alkoxides, more preferably sodium hydride or sodium methoxide.

The amount of the base used is usually 1.0 to 10.0mol, preferably 1.0 to 5.0mol, based on 1mol of the compound (IV).

When an acid is used in the present step, the acid used is not particularly limited as long as it is an acid generally used in organic chemical reactions, and examples thereof include inorganic acids such as hydrochloric acid, sulfuric acid, perchloric acid, and nitric acid; carboxylic acids such as formic acid, acetic acid and trifluoroacetic acid; sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and trifluoromethanesulfonic acid; amine salts such as pyridine-p-toluenesulfonate; phosphoric acids such as phosphoric acid and polyphosphoric acid; lewis acids such as aluminum chloride, titanium tetrachloride and boron trifluoride etherate are preferably inorganic acids or sulfonic acids.

The amount of the acid used is usually 1.0 to 10.0mol, preferably 1.0 to 5.0mol, based on 1mol of the compound (IV).

When a solvent is used in this step, the solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, and examples thereof include alcohols such as methanol, ethanol, propanol, and tert-butanol; ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, diethoxymethane and dioxane; aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene; nitriles such as acetonitrile; amides such as N, N-dimethylformamide, N-dimethylacetamide and N-methyl-2-pyrrolidone; sulfoxides such as dimethyl sulfoxide and sulfolane; halogenated hydrocarbons such as methylene chloride and chloroform; esters such as ethyl acetate and ethyl propionate; aliphatic hydrocarbons such as hexane, cyclohexane and heptane; pyridines such as pyridine and picoline; alternatively, the mixed solvent is preferably an ether, an aromatic hydrocarbon or an amide, and more preferably dimethoxyethane, toluene, N-dimethylformamide, N-dimethylacetamide or 1, 3-dimethyl-2-imidazolidinone.

The amount of the solvent used is usually 1.0 to 20 liters, preferably 1.0 to 10 liters, based on 1mol of the compound (IV).

(Process E)

In the formula, R and R^aThe same definitions as above are indicated.

This step is a step of reacting compound (IV) with compound (VI) in an inert solvent or in the absence of a solvent in the presence of a base or an acid to prepare compound (II).

The amount of the compound (VI) used in the present step is usually 1.0 to 10.0mol, preferably 1.0 to 5.0mol, based on 1mol of the compound (IV).

When a base is used in this step, the base to be used is not particularly limited as long as it is usually at a pH of 8 or more, and may be, for example, a hydroxide of an alkali metal such as sodium hydroxide or potassium hydroxide; hydroxides of alkaline earth metals such as calcium hydroxide and magnesium hydroxide; carbonates of alkali metals such as sodium carbonate and potassium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; metal hydrides such as sodium hydride and potassium hydride; alkoxides such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; organic bases such as triethylamine, N-dimethylaniline and pyridine; or organic metals such as methyllithium, butyllithium, methylmagnesium bromide, lithium diisopropylamide, etc., preferably hydroxides, metal hydrides or alkoxides of alkali metals, and more preferably sodium hydride or sodium methoxide.

When an acid is used in the present step, the acid used is not particularly limited as long as it is an acid generally used in organic chemical reactions, and examples thereof include inorganic acids such as hydrochloric acid, sulfuric acid, perchloric acid, and nitric acid; carboxylic acids such as formic acid, acetic acid and trifluoroacetic acid; sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and trifluoromethanesulfonic acid; amine salts such as pyridine-p-toluenesulfonate; phosphates such as phosphoric acid and polyphosphoric acid; lewis acids such as aluminum chloride, titanium tetrachloride and boron trifluoride etherate are preferably inorganic acids or sulfonic acids.

When a solvent is used in this step, the solvent used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent, and examples thereof include ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, diethoxymethane, and dioxane; aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene; nitriles such as acetonitrile; amides such as N, N-dimethylformamide, N-dimethylacetamide and N-methyl-2-pyrrolidone; sulfoxides such as dimethyl sulfoxide and sulfolane; halogenated hydrocarbons such as methylene chloride and chloroform; esters such as ethyl acetate and ethyl propionate; aliphatic hydrocarbons such as hexane, cyclohexane and heptane; pyridines such as pyridine and picoline; alternatively, the mixed solvent is preferably an ether, an aromatic hydrocarbon or an amide, and more preferably dimethoxyethane, toluene or N, N-dimethylformamide.

(Process F)

Wherein R and A are as defined above.

This step is a step of preparing a compound (VII) by adding a base to a compound (II) in an inert solvent.

The base used in the present step is not particularly limited as long as it is a base having a pH of usually 8 or higher, and may be, for example, a hydroxide of an alkali metal such as sodium hydroxide or potassium hydroxide; hydroxides of alkaline earth metals such as calcium hydroxide and magnesium hydroxide; carbonates of alkali metals such as sodium carbonate and potassium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; metal hydrides such as sodium hydride and potassium hydride; alkoxides such as sodium methoxide, sodium ethoxide and potassium tert-butoxide; organic bases such as triethylamine, N-dimethylaniline and pyridine; or organic metals such as methyllithium, butyllithium, methylmagnesium bromide, lithium diisopropylamide, etc., preferably alkali metal hydroxides, alkali metal carbonates, alkali metal bicarbonates, metal hydrides or alkoxides, and more preferably sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride or sodium methoxide.

The amount of the base used is usually 1.0 to 10.0mol, preferably 1.0 to 5.0mol, based on 1mol of the compound (II).

The solvent to be used is not particularly limited as long as it dissolves the starting material to a certain extent without inhibiting the reaction, and examples thereof include alcohols such as methanol, ethanol, propanol and tert-butanol; ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, diethoxymethane and dioxane; aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene; nitriles such as acetonitrile; amides such as N, N-dimethylformamide, N-dimethylacetamide and N-methyl-2-pyrrolidone; sulfoxides such as dimethyl sulfoxide and sulfolane; halogenated hydrocarbons such as methylene chloride and chloroform; esters such as ethyl acetate and ethyl propionate; aliphatic hydrocarbons such as hexane, cyclohexane and heptane; pyridines such as pyridine and picoline; alternatively, the mixed solvent is preferably an alcohol, an ether, an aromatic hydrocarbon or an amide, and more preferably methanol, ethanol, toluene or N, N-dimethylformamide.

The amount of the solvent used is usually 1.0 to 20 liters, preferably 1.0 to 10 liters, based on 1mol of the compound (II).

(Process G)

Wherein R represents the same definition as above, A^aRepresents cyano or carbamoyl.

This step is a step of preparing compound (VIII) by hydrolyzing compound (VIIa) in which a is a cyano group or a carbamoyl group in compound (VII) with addition of an acid or a base to a solvent, and may be carried out under ordinary hydrolysis conditions.

The acid used in the present step is not particularly limited as long as it is an acid generally used for hydrolysis, and may be, for example, an inorganic acid such as hydrochloric acid or sulfuric acid, and preferably hydrochloric acid or sulfuric acid.

The amount of the acid used is usually in an excess amount of 1 equivalent to a large amount relative to compound (VIIa).

The alkali used in the present step is not particularly limited as long as it is an alkali generally used for hydrolysis, and may be, for example, an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide, preferably sodium hydroxide or potassium hydroxide.

The amount of the base used is usually 1 to 20 equivalents relative to compound (VIIa).

The solvent used is not particularly limited as long as it is a solvent generally used for hydrolysis, and may be, for example, water; alcohols such as methanol, ethanol, propanol, and tert-butanol; ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, diethoxymethane and dioxane; alternatively, a mixed solvent thereof is preferably water.

The reaction temperature varies depending on the raw material compound, the reaction reagent, the solvent and the like, and is usually 0 ℃ to reflux temperature.

The reaction time varies depending on the raw material compound, the reaction reagent, the solvent, the reaction temperature, and the like, and is usually 5 minutes to 48 hours.

(Process H)

Wherein R represents the same definition as above.

This step is a method for producing the compound (IX) by reacting the compound (VIII) in which A is a carboxyl group in the compound (VII) with a halogenating agent in an inert solvent.

The halogenating agent used in the present step is not particularly limited as long as it is a reagent generally used for dehydration and halogenation reaction, and examples thereof include sulfur halides such as thionyl chloride and sulfuryl chloride; phosphorus halides such as phosphorus pentachloride; alternatively, organic halides such as phosgene, dicarbonyl chloride, tricarbonyl chloride and oxalyl chloride are preferably sulfur halides or organic halides, and more preferably thionyl chloride or sulfuryl chloride.

The solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to a certain extent, and examples thereof include ethers such as dimethyl ether, tert-butyl methyl ether, dimethoxyethane, tetrahydrofuran and dioxane; aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene; nitriles such as acetonitrile; amides such as N, N-dimethylamide, N-dimethylacetamide and N-methyl-2-pyrrolidone; halogenated hydrocarbons such as methylene chloride and dichloroethane; esters such as ethyl acetate and propyl acetate; aliphatic hydrocarbons such as hexane, cyclohexane and heptane; pyridines such as pyridine and picoline; alternatively, the mixed solvent is preferably an ether, an aromatic hydrocarbon or a halogenated hydrocarbon, and more preferably toluene, xylene or dichloroethane.

The amount of the halogenating agent used in the present step is usually 1.0 to 10.0mol, preferably 1.0 to 5.0mol, based on 1mol of the compound (VIII).

The amount of the solvent used is usually 0.1 to 20.0 liters, preferably 0.5 to 10 liters, based on 1mol of the compound (VIII).

The reaction temperature varies depending on the raw material compound, the reaction reagent, the solvent, etc., and is usually-40 ℃ to 150 ℃, preferably 0 ℃ to the reflux temperature of the solvent.

After the completion of each reaction, the target compound in each step can be recovered from the reaction mixture by a conventional method. For example, it can be obtained by suitably neutralizing the reaction mixture or removing it by filtration in the presence of insoluble matter, adding a water-immiscible organic solvent, washing with water, and distilling off the solvent. The target compound obtained may be further purified by a conventional method such as recrystallization, reprecipitation or chromatography, if necessary. The target compound in each step may be used in the subsequent reaction step without purification.

When the compound of the present invention is used as an active ingredient of an agricultural chemical, the compound of the present invention may be used as it is, but may be formulated into various forms such as an emulsion, a suspension, a powder, a granule, a tablet, a wettable powder, an aqueous solvent, a liquid, a flowable agent, a wettable granule, an aerosol, a paste, an oil preparation, an emulsion, etc. by blending a carrier, a surfactant and other adjuvants which are generally used in formulation as an agricultural chemical adjuvant. The mixing ratio of the components is usually 0.1-9.0 parts by mass of the effective components and 10-99.9 parts by mass of the pesticide adjuvant.

The carrier used in the preparation may be, for example, a solid carrier such as animal or plant powder including starch, activated carbon, soybean powder, wheat flour, wood powder, fish powder and milk powder, or mineral powder including talc, kaolin, bentonite, calcium carbonate, zeolite, diatomaceous earth, silica, clay and alumina; alternatively, the carrier liquid may be a solid carrier or a liquid carrier, and is preferably a solid carrier or a liquid carrier, such as water, alcohols such as isopropyl alcohol and ethylene glycol, ketones such as cyclohexane and methyl ethyl ketone, ethers such as dioxane and tetrahydrofuran, aliphatic hydrocarbons such as kerosene and light oil, aromatic hydrocarbons such as xylene, trimethylbenzene, tetramethylbenzene, methylnaphthalene and solvent naphtha, halogenated hydrocarbons such as chlorobenzene, amides such as dimethylacetamide, esters such as glycerol esters of fatty acids, nitriles such as acetonitrile, and sulfur-containing compounds such as dimethyl sulfoxide.

The surfactant used may be, for example, a metal salt of an alkylbenzenesulfonic acid, a metal salt of dinaphthylmethane disulfonic acid, a salt of an alcohol sulfate, an alkylaryl sulfonate, a lignosulfonate, a polyoxyethylene glycol ether, a polyoxyethylene alkylaryl ether or a polyoxyethylene sorbitan monoalkylate, and is preferably a metal salt of an alkylbenzenesulfonic acid, a lignosulfonate, a polyoxyethylene alkylaryl ether or a polyoxyethylene sorbitan monoalkylate.

Examples of the other auxiliary agents include binders or tackifiers such as carboxydimethyl cellulose, gum arabic, sodium alginate, xanthan gum, guar gum, tragacanth gum, and polyvinyl alcohol; defoaming agents for metal soaps and the like; alternatively, physical property improvers and colorants such as fatty acids, alkyl phosphates, silicones, and paraffins are preferably guar gum or xanthan gum.

These preparations may be used as they are in actual use, or may be diluted with a diluent such as water to a predetermined concentration and then used. The application of the various preparations containing the compound of the present invention or the diluent thereof may be a commonly performed application method, that is, spreading (e.g., spraying, atomizing (misting), atomizing (atomizing), dusting, shot-grain, water-surface application, tank application, etc.), soil application (e.g., mixing, pouring, etc.), surface application (e.g., coating, powder coating, covering, etc.), dipping, poison bait, or the like. In addition, the effective components are mixed with feed for feeding livestock, and the occurrence and breeding of pests in excrement, especially harmful insects can be prevented. Alternatively, the application may be carried out by a so-called ultra-high concentration small amount dispersion method. In this method, 100% of the active ingredient may be contained.

The concentration of the active ingredient in the application of the agricultural chemical of the present invention is usually 0.1 to 50000ppm, preferably 1 to 10000 ppm. However, the concentration of the active ingredient may be appropriately changed depending on the form of the preparation, the method, purpose, timing, location of application, and the occurrence state of the pest, and for example, in the case of aquatic pest, since the concentration of the active ingredient in water is smaller than the above range, the control may be performed by spraying the chemical liquid at the above concentration to the occurrence location. The amount of the agricultural chemical of the present invention to be used is, for example, 0.1 to 5000g, preferably 1 to 1000g per 10 mu of the compound as an active ingredient in the case of soil mixing treatment.

Although the compound of the present invention is not sufficiently effective when used alone, it may be used in combination with a fertilizer and other agricultural chemicals, for example, insecticides, acaricides, nematocides, bactericides, antivirals, attractants, herbicides, plant regulators, etc., if necessary, and even more excellent effects are exhibited in such cases.

As other agricultural chemicals which can be used in combination with the compound of the present invention, there may be mentioned, for example, insecticides, acaricides, nematicides, bactericides, antiviral agents, attractants, herbicides and plant regulators, and preferably insecticides, acaricides, nematicides, bactericides or herbicides.

The insecticide used may be, for example, organophosphorus and carbamate insecticides, ピレスロイド series insecticides, or other insecticides.

Organophosphorus and carbamate insecticides, for example, fenthion, fenitrothion, diazinon, chlorpyrifos, オキシデプホス, aphidicol, フエントエ - ト, dimethoate, nor, malasone, trichlorfon, fosetyl methyl, ホスメツト, dichlorvos [ ジクロルホス ], acephate, EPBP, methyl-hexa-penta, オキシジメトン methyl, ethion, ジオキサベンゾホス, cyanophos, isoxazolide, phosmet, vozaphos, methidathion, スルプロホス, chlorfenvinphos, テトラクロルビンホス, dimethyl ビンホス, propaphos [ プロパホス ], イソフエンホス, fosetyl, プロフエノホス, ピラクロホス, モノクロトホス, glutethion, アルジカルブ, methomyl, チオジカルブ, carbofuran, カルボスルフアン, ベンフラカルブ, フラチオカルブ, プロポキスル, フエノブカルブ, メトルカルブ, イソプロカルブ, carbaryl, ピリミカ - ブ, エチオフエンカルブ, fenamiphos, ピリミホス methyl, キナルホス, methyl chlorfenapyr, プロチオホス, ナレツド, EPN, XMC, ベンダイオカルブ, オキサミル, アラニカルブ or クロル ethoxy ホス.

ピレスロイド series of insecticides, can be, for example, ペルメトリン, シペルメトリン, デルタメトリン, フエンバレレ - ト, フエンプロパトリン, pyrethrin, pyrethrum, テトラメトリン, レスメトリン, ジメスリン, プロパスリン, フエノトリン, プロトリン, フルバリネ - ト, シフルトリン, シ halo トリン, フルシトリネ - ト, エトフエンプロツクス, ring プロトリン, トラロメトリン, シラフルオフエン, テフルトリン, ビフエントリン or アクリナトリン.

Other insecticides, which may be, for example, ジフルベンズロン, クロルフルアズロン, ヘキサフルムロン, トリフルムロン, テフルベンズロン, フルフエノクスロン, フル ring クスロン, ブプロフエジン, ピリプロキシフエン, ルフエヌロン, シロマジン, メトプレン, endosulfan, ジアフエンチウロン, イミダクロプリド, フイプロニル, phenoxy カルブ, badan, thiocyclam, monosultap, テブフエノジド, クロルフエナピル, エマメクチンベンゾエ - ト, アセタミプリド, ニテンピラム, ピメトロジン, sodium oleate, sulfuric acid ニコチン, ロテノン, メタアルデヒド, マシン oil, なたね oil, BT agents, insect pathogen ウイルス, and the like.

The acaricide can be, for example, dicofol, bromopropylate, Kalopanax, アミトラズ, プロパルギツト, ベンゾメ - トヘキシチアゾツクス, フエンブタチンオキシド, ポリナクチン, chlorfenapyr, miticide, テトラジホン, アバメクチン, ミルベメクチン, クロフエンテジン, ピリダベン, フエンピロキシメ - ト, テブフエンピラド, ピリミジフエン, フエノチオカルブ, ジエノクロル, エトキサブ - ルハルフエンプロツクス。

The nematicide used may be, for example, フエナミホス, ホスチアゼ - ト, エトプロホス, methyl イソチオシアネ - ト, 1, 3-dichloropropene or DCIP.

The bactericide to be used may be, for example, チオフアネ - ト methyl group, benomyl, carbendazim, チアベンダゾ - ル, folpet [ フオルベツト ], チウラム, ziram, zineb, マンネブ, マンゼブ, ポリ carbamate, イプロベンホス, エジフエンフオス, tetrachlorophthalide, thiabendazole (thiabendazole), isoprothiolane, chlorine タロニル, captan (Kepton), ポリオキシン, blasticidin, kasugamycin, streptomycin, バリダマイシン, triazolothiazine, pyroquinone, cumin, Basidion, flutolamide, ペン ring ン, iprodione, ヒメキサゾ - ル, metalaxyl, トリフルミゾ - ル, トリホリン, トリアジメホン, ビテルタノ - ル, フエナリモル, プロピコナゾ - ル, シモキサニル, ポロクロラズ, ペフラゾエ - ト, ヘキサコナゾ - ル, ミクロブタニル, ジクロメジン, テクロフタラム, propineb, dithianon, ホセチル, ビンクロゾリン, プロシミドン, オキサジキシル, グアザチン, プロパモカルブ hydrochloride, フルアジナム, オキソリニツク acid, ヒドロキシイソキサゾ - ル, イミベンコナゾ - ル or メパニピリム.

The herbicide to be used may be, for example, ジフルフエニカン, propanil, dichloro ピコ phosphoric acid, dicamba, ピコロラム, 2, 4-D, 2, 4-DB, 2, 4-DP, フルロキシピル, MCPA, MCPP, トリクロピル, ジクロホツプ -methyl, フエノキサプロツプ -ethyl, フルアジホツプ -butyl, halogeno キシホツプ -methyl, キザロホツプ -ethyl, ノルフルラゾン, chlorpropham [ クロルブロフアム ], デスメジフアム, dipheny, プロフアム, oxabetel, アセトクロル, norfluramine, メタザクロル, メトラクロル, プレチラクロル, プロパクロル, オリザリン, トリフルラリン, アシフルオルフエン, diclofop, benfop, benazolin, etc, ビフエノツクス, fluorine グリゴフエン, ホメサフエン, halogeno サフエン, ラクトフエン, オキシフルオルフエン, クロルトルロン, ジウロン, フルオメツロン, イソプロツロン, リヌロン, メタベンズチアズロン, アロキシジム, クレトジム, シクロキシジム, セトキシジム, トラコキシジム, イマゼタピル, イマザメタベンズ, イマザピル, イマザキン, ブロモキシニル, dichlobenil, イオキシニル, メフエナセツト, amide スルフロン, ベンスルフロン -methyl, クロリムロン -ethyl, クロルスルフロン, シノスルフロン, メトスルフロン -methyl, ニコスルフロン, ピリミスルフロン, ピラゾスルフロン -ethyl, チフエンスルフロン -methyl, トリアスルフロン, トリベヌロン -methyl, ブチレ - ト, シクロエ - ト, molinate, EPTC, エスプロカルプ, chum, プロスルホカルプ, ベンチオカルプ, トリアレ - ト, atrazine, シアナジン, simazine, simetryn, タ - ブトリン, タ - ブチラジン, ヘキサジノン, メタミトロン, メトリブジン, アミトリアゾ - ル, ベンフレセ - ト, ベンタゾン, シンメチリン, クロマゾン, クロピラリド, ジフエンゾクアツト, ジチオピル, エトフメセ - ト, フルオロクロリドン, グルホシネ - ト, グリホセ - ト, イソキサベン, ピリデ - ト, キンクロラツク, キンメタツク, スルホセ - ト or トリジフアン.

The compounds of the present invention exhibit excellent controlling effects against, for example, hemiptera pests, lepidopteran pests, coleopteran pests, dipteran pests, hymenopteran pests, orthopteran pests, isopteran pests, thysanopteran pests, spider mites, and plant-parasitic nematodes. Moreover, the compounds of the present invention also exhibit excellent controlling effects on other harmful animals, unpleasant animals, sanitary pests and parasites.

Examples of hemipteran pests include, for example, ホソヘリカメムシ (Riptortus clavatus), ミナミアオカメムシ (Nezara viridula), メクラカメムシ (Lygus sp.), アメリカコバネナガカメムシ (Blissus leucopterus), カメムシ (Heteroptera) such as ナシグンバイ (Stephaniae nashi), ツマグロヨコバイ (Nephora), ヒメヨコバイ (Emposaca, Erythroneura sp., Circifier sp.) and ヨコバイ (Nilaparatolugens), セジロウンカ (Sogatella furcifera), ヒメトビウンカ (Laodelphax striatellus) and ウンカ (Laodelphax striatellus), キジラミ (Psyllia sp.and タバココナジラミ (Beysia tabaci), シツコナジラミ (Triperoraluronium), Myzuria (Mycelius) such as Mycelius, Myceliac), and Mycelius 2 (Myceliac) リンゴアブラムシ (Aphis pomi), ワタアブラムシ (Aphis gossypii), Aphis fabae, ニセダイコンアブラムシ (Liparis erysimi), ジヤガイモヒゲナガアブラムシ (Austorhum solani), アブラムシ types of ムギミドリアブラムシ (Schizaphis graminum), クワコナカイガラムシ (Pseudococcus comstocki), ルビ - ロウムシ (Ceroplastrubes), サンホ - ゼカイガラムシ (Comstockaspens), ヤノエカイガラムシ (Unnaspys yanoensis), カイガラムシ and サシガメ (Rhodnius sp.).

Examples of lepidopteran pests include, for example, チヤハマキ (Homoniagnina), コカクモンハマキ (Adoxophyesonana), テングハマキ (Sparganothris pileriana), ナシヒメシンクイ (Grapholitha molesta), マメシンクイガ (Leguivora), コドリンガ (Laspeyresia pomonella), ハマキガ (Eucosa sp., Lobesiabotrana, etc.), ブドウホソハマキ (Euporium biguella), ホソハマキガ (such as, for example, Bambalinia sp., ミノガ (Bambalinia sp., etc.), コクガ (Nemapnogen grandis), イガ (Tineapoliella), etc., ヒロズコガ (ギンモンハモグリガ (Lyetiporium biguella), etc., ハモグリガ (Phenylone sp), 6324 (Synechocystinella), etc., Synloniella, ミカンハモグリガ (Lysionella), etc. (Protozoa, etc.), コナガ (Protozoa, コナガ, etc.), 6324 (Plutozoa, etc., Plutozoa, P コナガ, etc.), 4624 (Plutozoa, コナガ, etc., of Nodysboli, No. by Novosylvestris, No. 5, No. コナガ, No. 5, No., ワタアカミムシ (Pentinophora gossypiella), ジヤガイモガ (Phermatoepercocculla), キバガ class of Stomophoryx sp. et al, シンクイガ class of モモシンクイガ (Carposina nipponensis) et al, イラガ class of イラガ (Monema flavscens) et al, ニカメイガ (Chilo supressalis), コブノメイガ (Cnaphalocrasis medinalis), Ostrinia nubilalis, アワノメイガ (Ostrinia furnacalis), ハイマダラノメイガ (Hellula undalis) ハチミツガ (Galleria mellonella), Elasmopalsus lignosporaneus, Loxoge sticalis et al, メイガ class of モンシロチヨウ (Pieri rapae) et al, シロチヨウ class of Manyle ヨモギエダシヤク (Ascotiella シヤクガ, 6862 (Lipocalia) et al, 368653 class of Hypopha, 3655 (Hypericum, 3655 family of Hypocrypsinaria), 368653 class of Euschistospora 8653 et al, 3655 class of Hypocrypsinaria, 368653, 3655 class of Hypocrea, 3655, 8653, and so on, タバコバツドワ - ム (Heliothis virescens), ボ - ルワ - ム (Helicoverpa zea), シロイチモジヨトウ (Spodoptera exigua), オオタバコガ (Helicoverpa armigera), ハスモンヨトウ (Spodoptera litura), ヨトウガ (Mamestra fibre), タマナヤガ (Agrotis ipsilon), アワヨトウ (pseudo fatia separatata) and イラクサキンウワバ (Trichoplusia ni), etc. of ヤガ type.

Examples of the coleopteran pests include ドウガネブイブイ (Anamalacia cupra), マメコガネ (Popillia japonica), ヒメコガネ (Anamalala rufocera), コガネムシ types of Eutheoruduces and the like, ワイヤ - ワ - ム (Agricotes sp), コメツキムシ types of Conodeus sp.and the like, ニジユウヤホシテントウ (Epilachnologicotinctorontata), テントウムシ types of インゲンテントウムシ (Epilachnologicovia varivestis) and the like, ゴミムシダマシ types of コクヌストモドキ (Tribolium castaneum) and the like, ゴマダラカミキリ (Anaplastic), カミキリムシ types of Monochamus alternatus and the like, インゲンマメゾウムシ (Acanthoscelides 695s), マメゾウムシ types of Dianthus chinensis and the like, 8253 types of Lenticular 8653, 368672 (Oczaema 8672), 368672 (Oczama castaneta) and the like, 368672 (Ocular castalema castaneta) and the like, テンサイトビハムシ (Chaetocnema connna), Phaedon cochlearia, Oulema melanopus, Dicladispa armigera et al, Apion godmani et al, ホソクチゾウムシ, イネミズゾウムシ (Lissophorus oryzae), ゾウムシ, ワタミゾウムシ (Anthonomonus grandis), オサゾウムシ, キクイムシ, カツオブシムシ, and シバンムシ, for example, コクゾウムシ (Sitophilus zeamais).

As the dipteran pests, for example, キリウジガガンボ (Tipula aino), イネユスリカ (chironomy oryzae), イネシントメタマバエ (Orseolia oryzae), チチユウカイミバエ (Ceratitis capitata), イネミギワバエ (Hydrellia griseola), オウトウシヨウジヨウバエ (Drosophila suzukii), フリツツフライ (Oscinella front), イネカラバエ (Chlorops oryzae), インゲンモグリバエ (Ophiomyia phaseoli), マメハモグリバエ (Liriomyza trifolii), アカザモグリハナバエ (Pegomya hysocyami), タネバエ (Delia platura), ソルガムフライ (Atherona society), イエバエ (Musca domastica), ウマバエ (Gastrophilus sp.), サシバエ (Stomoxys sp., Aedes 356 (Aegea gpague), Cuilex (Cuilex), Anemophilus (シナハマダラカ) and Cureophys コガタアカイエカ (Curie).

As membranous pests, there are, for example, クキバチ (Cephus sp.), カタビロコバチ (Harmolita sp.), カブラハバチ (Athalia rosae), スズメバチ (Vespa mandarina) and フアイア - アント.

As orthoptera pests, there can be mentioned, for example, チヤバネゴキブリ (Blattella germanica), ワモンゴキブリ (Periplaneta americana), ケラ (Gryllotalpaaflora), バツタ (Loustamitororia), and Melanoplus sanguinipes.

Examples of the isopteran pests include ヤマトシロアリ (Reticulitermes speratus), イエシロアリ (coptottermes formosanus) and ダイコクシロアリ (Cryptotermes domestius).

Examples of pests from the order of the Thysanoptera include チヤノキイロアザミウマ (Scithotrips dorsalis), ミナミキイロアザミウマ (Thrips palmi), クロトンアザミウマ (Heliothrips haloid), ミカンキイロアザミウマ (Frankliniella occidentalis), and イネクダアザミウマ (Haplothrips aculeatus).

Examples of the spider mites include ナミハダニ (Tetranychus urticae), カンザワハダニ (Tetranychus urticae), ミカンハダニ (Pannychus citri), リンゴハダニ (Pannychus ulmi), イエロ - マイト (Eotetranychus carpini), テキサスシトラスマイト (Eotetranychus banksi), ミカンサビダニ (Aculops pelekassi), チヤノホコリダニ (polyphagorsemus latus), ヒメハダニ (Brevipus sp.), ロビンネダニ (Rhizosaccharomyces robini) and ケナガコナダニ (Typhagus putrescentiae).

Examples of plant-parasitic nematodes include サツマイモネコブセンチユウ (Meloidogyne incognita), ネグサレセンチユウ (Pratlenylchus sp.) ダイズシストセンチユウ (Heterodera glycines), イネシンガレセンチユウ (Aphelenchoides besseyi) and マツノザイセンチユウ (Bursereenchus lignicolus).

Examples of other harmful animals, unpleasant animals, sanitary pests and parasites include animals 4642 such as Pomacea canadensita, ナメクジ (Incilaria sp.), アフリカマイマイ (Achatina furica), gastropodia (Gastropoda), ダンゴムシ (Armadillidium sp.), Isopoda (Isopoda) such as ワラジムシ and ムカデ, チヤタテムシ such as Liposophilus sp, シミ such as Ctenotrepisa sp, ノミ such as Pulex sp and Ctenocepha sp, ハジラミ such as Trichoderma sp, トコジラミ such as Cimex sp, オウシマダニ (Boophilus micropulus), and parasitic ダニ such as Haemaphysaliensis, and parasitic 3884.

Further, the compound of the present invention is also effective against pests resistant to organophosphorus compounds, carbamate compounds, synthetic ピレスロイド compounds, アミドウレア compounds, or conventional insecticides.

Detailed Description

The compounds of the present invention will be specifically described below by way of examples, reference examples, formulation examples and test examples, but the present invention is not limited thereto.

(example 1)

N- (3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-2, Process A-1)

5-amino-3-methylisoxazole (147mg, 1.5mmol) was dissolved in dimethylformamide (5ml), and sodium hydride (60% in mineral oil, 72mg, 1.8mmol) was added under ice-cooling, followed by addition of 4-trifluoromethylnicotinoyl chloride (314mg, 1.5mmol), and heating and stirring were carried out at 80 ℃ for 2 hours. The reaction solution was poured into ice water, and extracted with ethyl acetate. The organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by thin layer chromatography (developing solvent: ethyl acetate/hexane: 1/1) to give the title compound (181mg, yield 44%).

¹H-NMR(CDCl₃)δ(ppm)：10.35(1H，brd.s)，8.91(1H，s)，8.88(1H，d，J＝5.1Hz)，7.66(1H，d，J＝5.1Hz)，6.41(1H，s)，2.27(3H，s)。

Melting point: 53-55 ℃.

(example 2)

N-ethoxymethyl-N- (3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-51, Process A-2)

N- (3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (compound No. 1-2, 107.1mg, 0.39mmol) obtained in example 1 was dissolved in dimethylformamide (2ml), and potassium carbonate (81.4mg, 0.59mmol) and bromoacetonitrile (30 μ L, 0.43mmol) were added to the solution, followed by stirring at room temperature for 2 hours. The reaction solution was poured into water, extracted with ethyl acetate, and the extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by thin layer chromatography (developing solvent: hexane/ethyl acetate 1/1) to give the title compound (91.3mg, yield 75%).

¹H-NMR(DMSO-d₆)δ(ppm)：8.93(1H，d，J＝5.1Hz)，8.85(1H，s)，7.90(1H，d，J＝5.1Hz)，6.28(1H，s)，5.22(2H，s)，3.59(2H，q，J＝7.0Hz)，2.12(3H，s)，1.11(3H，t，J＝7.0Hz)。

Physical properties: an oil.

(example 3)

N- (4-chloro-3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-21, Process B)

To N- (3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (compound No. 1-2, 101.7mg, 0.37mmol) obtained in example 1 were added carbon tetrachloride (2ml) and N-chlorosuccinimide (64.6mg, 0.48mmol), and the mixture was refluxed for 1.5 hours. The reaction solution was poured into water, extracted with ethyl acetate, and the extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by thin layer chromatography (developing solvent: hexane/ethyl acetate 1/1) to give the title compound (69.3mg, yield 61%).

¹H-NMR(CDCl₃)δ(ppm)：8.94(1H，s)，8.92(1H，d，J＝5.1Hz)，8.41(1H，brd.s)，7.67(1H，d，J＝5.1Hz)，2.29(3H，s)。

Melting point: 153-156 ℃.

Further, the following compounds were prepared based on any of examples 1 to 3.

(example 4)

N- (5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-1)

¹H-NMR(CDCl₃)δ(ppm)：10.07(1H，brd.s)，8.94(1H，s)，8.91(1H，d，J＝5.1Hz)，8.19(1H，d，J＝1.8Hz)，7.56(1H，d，J＝5.1Hz)，6.56(1H，d，J＝1.8Hz)。

Physical properties: is amorphous.

(example 5)

N- (3-Ethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-3)

¹H-NMR(CDCl₃)δ(ppm)：10.01(1H，brd.s)，8.92(1H，s)，8.90(1H，d，J＝5.1Hz)，7.68(1H，d，J＝5.1Hz)，6.45(1H，s)，2.66(2H，q，J＝7.7Hz)，1.28(3H，t，J＝7.7Hz)。

Physical properties: an oil.

(example 6)

N- (3-isopropyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-5)

¹H-NMR(CDCl₃)δ(ppm)：10.31(1H，brd.s)，8.91(1H，s)，8.89(1H，d，J＝5.1Hz)，7.67(1H，d，J＝5.1Hz)，6.46(1H，s)，3.01(1H，m)，1.29(6H，d，J＝7.0Hz)。

Physical properties: an oil.

(example 7)

N- (3-formyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-16)

¹H-NMR(CDCl₃)δ(ppm)：10.10(1H，s)，8.98(1H，d，J＝5.1Hz)，8.97(1H，s)，7.71(1H，d，J＝5.1Hz)，6.93(1H，s)。

Physical properties: is amorphous.

(example 8)

N- (3-Oximethylmethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-17)

¹H-NMR(CDCl₃)δ(ppm)：8.97(1H，d，J＝5.1Hz)，8.96(1H，s)，8.08(1H，s)，7.86(1H，d，J＝5.1Hz)，6.72(1H，s)。

Physical properties: is amorphous.

(example 9)

N- (3-cyano-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-18)

¹H-NMR(CDCl₃)δ(ppm)：8.94(1H，d，J＝5.1Hz)，8.91(1H，s)，7.73(1H，d，J＝5.1Hz)，6.90(1H，s)。

Melting point: 135 ℃ and 139 ℃.

(example 10)

N- (3-methoxymethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-19)

¹H-NMR(CDCl₃)δ(ppm)：9.90(1H，brd.s)，8.93(1H，s)，8.92(1H，d，J＝5.1Hz)，7.69(1H，d，J＝5.1Hz)，6.60(1H，s)，4.50(2H，s)，3.42(3H，s)。

Physical properties: is amorphous.

(example 11)

N- (4-chloro-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-20)

¹H-NMR(CDCl₃)δ(ppm)：8.94(1H，s)，8.91(1H，d，J＝5.1Hz)，8.27(1H，s)，7.67(1H，d，J＝5.1Hz)。

Physical properties: an oil.

(example 12)

N- (4-chloro-3-cyclopropyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-25)

¹H-NMR(CDCl₃) δ (ppm): 8.96(1H, brd.s), 8.90-8.84(2H, m), 7.65(1H, d, J ═ 5.1Hz), 1.94-1.80(1H, m), 1.08-1.04(4H, m). Physical properties: is amorphous.

(example 13)

N- (4-chloro-3-methoxymethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-37)

¹H-NMR(CDCl₃)δ(ppm)：8.92(1H，s)，8.91(1H，d，J＝5.1hz)，7.67(1H，d，J＝5.1Hz)，4.51(2H，s)，3.42(3H，s)。

Melting point: 69-72 ℃.

(example 14)

N- (4-bromo-3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-41)

¹H-NMR(CDCl₃)δ(ppm)：8.92(1H，s)，8.90(1H，d，J＝5.1Hz)，7.66(1H，d，J＝5.1Hz)，2.29(3H，s)。

Melting point: 165-166 ℃.

(example 15)

N- (4-iodo-3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-43)

¹H-NMR(CDCl₃)δ(ppm)：8.97(1H，s)，8.95(1H，d，J＝5.1Hz)，7.68(1H，d，J＝5.1Hz)，2.30(3H，s)。

Melting point: 198 ℃ and 201 ℃.

(example 16)

N-methyl-N- (3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-47)

¹H-NMR(DMSO-d₆)δ(ppm)：8.92(1H，d，J＝5.2Hz)，8.85(1H，s)，7.83(1H，d，J＝5.2Hz)，6.06(1H，brd.s)，3.36(3H，s)，2.12(3H，s)。

Physical properties: an oil.

(example 17)

N-allyl-N- (5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-48)

¹H-NMR(DMSO-d₆)δ(ppm)：8.89(1H，d，J＝5.2Hz)，8.78(1H，s)，7.81(1H，d，J＝5.2Hz)，6.05(1H，s)，5.95-5.80(1H，m)，5.29-5.19(2H，m)，4.44(2H，d，J＝5.8Hz)，2.08(3H，s)。

Physical properties: an oil.

(example 18)

N-allyl-N- (3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-49)

Physical properties: an oil.

(example 19)

N-cyanomethyl-N- (3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-53)

¹H-NMR(DMSO-d₆)δ(ppm)：8.96(1H，d，J＝5.1Hz)，8.91(1H，s)，7.92(1H，d，J＝5.1Hz)，6.24(1H，s)，5.09(2H，s)，2.11(3H，s)。

Physical properties: an oil.

(example 20)

N- (3-methyl-5-isoxazolyl) -N-methylthiomethyl-4- (trifluoromethyl) nicotinamide (Compound No. 1-55)

¹H-NMR(CDCl₃)δ(ppm)：8.82(1H，d，J＝5.1Hz)，8.63(1H，s)，7.58(1H，d，J＝5.1Hz)，5.68(1H，s)，5.05(2H，s)，2.29(3H，s)，2.16(3H，s)。

Physical properties: an oil.

(example 21)

N- (3-methyl- [1, 2, 4] oxadiazol-5-yl) -4- (trifluoromethyl) nicotinamide (Compound No. 2-2)

¹H-NMR(DMSO-d₆)δ(ppm)：8.70-9.10(2H，brd.s)，7.72(1H，brd.s)，2.16(3H，brd.s)。

Physical properties: an oil.

(example 22)

N- (4-chloro-3-cyano-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-36)

¹H-NMR(CDCl₃)δ(ppm)：9.05-8.95(2H，m)，7.71(1H，d，J＝5.1Hz)。

Physical properties: is amorphous.

(example 23)

N- (4-fluoro-3-cyano-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-38)

¹H-NMR(DMSO-d₆)δ(ppm)：11.98(1H，s)，9.10-9.03(3H，m)，7.95(1H，d，J＝5.2Hz)。

Melting point: 122 ℃ and 123 ℃.

(example 24)

N- (4-bromo-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-40)

¹H-NMR(CDCl₃)δ(ppm)：8.96(1H，s)，8.94(1H，d，J＝5.1Hz)，8.26(1H，s)，8.16(1H，s)，7.68(1H，d，J＝5.1Hz)。

Melting point: 98-100 ℃.

(example 25)

N- (4-iodo-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-42)

¹H-NMR(CDCl₃)δ(ppm)：8.99-8.96(2H，m)，8.24(1H，s)，7.91(1H，brd.s)，7.69(1H，d，J＝5.5Hz)。

Melting point: 176 ℃ and 178 ℃.

(example 26)

N- (3-diethoxymethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-56)

¹H-NMR(CDCl₃)δ(ppm)：9.80(1H，brd.s)，8.91(1H，s)，8.90(1H，d，J＝5.1Hz)，7.68(1H，d，J＝5.1Hz)，6.64(1H，s)，5.55(1H，s)，3.80-3.55(4H，m)，1.25(6H，t，J＝7.0Hz)。

Physical properties: is amorphous.

(example 27)

N-acetyl-N- (3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-57)

¹H-NMR(CDCl₃)δ(ppm)：8.85(1H，d，J＝5.1Hz)，8.75(1H，s)，7.57(1H，d，J＝5.1Hz)，6.17(1H，s)，2.35(3H，s)，2.31(3H，s)。

Physical properties: an oil.

(example 28)

N- (3-Methoxyiminomethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-58)

¹H-NMR(CDCl₃)δ(ppm)：8.84(1H，s)，8.79(1H，d，J＝5.1Hz)，7.94(1H，s)，7.66(1H，d，J＝5.1Hz)，6.81(1H，s)，4.02(3H，s)。

Melting point: 140 ℃ and 144 ℃.

(example 29)

N- (3-ethoxycarbonyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-59)

¹H-NMR(CDCl₃)δ(ppm)：8.94(1H，s)，8.90(1H，d，J＝5.1Hz)，7.67(1H，d，J＝5.1Hz)，6.92(1H，s)，4.43(2H，q，J＝7.3Hz)，1.41(3H，t，J＝7.3Hz)。

Physical properties: is amorphous.

(example 30)

5- [ N, N-bis (4-trifluoromethylnicotinoyl) ] aminoisoxazoles (Compound No. 1-60)

¹H-NMR(DMSO-d₆)δ(ppm)：9.30(1H，s)，9.14(1H，d，J＝4.9Hz)，9.01(2H，m)，7.98(1H，d，J＝5.2Hz)，7.91(1H，d，J＝5.2Hz)，7.78(1H，d，J＝10.2Hz)，5.09(1H，t，J＝9.9Hz)。

Physical properties: is amorphous.

(example 31)

N-ethoxymethyl-N- (4-iodo-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-61)

¹H-NMR(CDCl₃)δ(ppm)：8.79(1H，d，J＝4.8Hz)，8.66(1H，s)，8.11(1H，s)，7.57(1H，d，J＝5.1Hz)，5.38(2H，brd.s)，3.79(2H，d，J＝7.0Hz)，1.24(3H，t，J＝7.1Hz)。

Melting point: 114 ℃ and 116 ℃.

(example 32)

N- (4-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-62)

¹H-NMR(CDCl₃)δ(ppm)：11.52(1H，s)，9.09(1H，s)，9.02(1H，d，J＝5.1Hz)，8.49(1H，s)，7.94(1H，d，J＝5.1Hz)，1.95(3H，s)。

Melting point: 115 ℃ and 116 ℃.

(example 33)

N- (3, 4-dimethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-63)

¹H-NMR(CDCl₃)δ(ppm)：9.43(1H，brd.s)，8.88-8.79(2H，m)，7.63(1H，d，J＝5.1Hz)，2.17(3H，s)，1.95(3H，s)。

Melting point: 141 ℃ and 143 ℃.

(example 34)

N- (4-Ethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-64)

¹H-NMR(CDCl₃)δ(ppm)：8.91(1H，s)，8.90(1H，d，J＝5.1Hz)，8.65(1H，brd.s)，8.14(1H，s)，7.66(1H，d，J＝5.1Hz)，2.50(2H，q，J＝7.7Hz)，1.21(3H，t，J＝7.7Hz)。

Melting point: 136 and 137 ℃.

(example 35)

N- (4-propyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-65)

¹H-NMR(CDCl₃)δ(ppm)：8.90(1H，s)，8.88(1H，d，J＝5.1Hz)，8.11(1H，s)，7.65(1H，d，J＝5.1Hz)，2.51-2.31(2H，m)，1.65-1.54(2H，m)，0.96(3H，t，J＝7.3Hz)。

Melting point: 120 ℃ and 123 ℃.

(example 36)

N- (4-isopropyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-66)

¹H-NMR(CDCl₃)δ(ppm)：8.87(1H，s)，8.85(1H，d，J＝5.1)，8.13(1H，s)，7.64(1H，d，J＝5.1Hz)，3.00-2.93(1H，m)，1.21(6H，d，J＝7.0Hz)。

Physical properties: an oil.

(example 37)

N- (4-cyclopropyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-67)

¹H-NMR(CDCl₃)δ(ppm)：8.93(1H，s)，8.92(1H，d，J＝5.1Hz)，8.40(1H，brd.s)，7.94(1H，s)，7.67(1H，d，J＝5.1Hz)，1.88-1.55(1H，m)，1.05-0.80(2H，m)，0.65-0.45(2H，m)。

Melting point: 140 ℃ and 141 ℃.

(example 38)

N- (4-allyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-68)

¹H-NMR(CDCl₃)δ(ppm)：8.93(1H，s)，8.92(1H，d，J＝5.1Hz)，8.12(1H，s)，7.67(1H，d，J＝5.1Hz)，6.05-5.75(1H，m)，5.20-5.00(2H，m)，3.26(2H，d，J＝5.9Hz)。

Melting point: 93-97 ℃.

(example 39)

N- (4-butyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-69)

¹H-NMR(CDCl₃)δ(ppm)：9.02(1H，brd.s)，8.89(1H，s)，8.87(1H，d，J＝5.1Hz)，8.10(1H，s)，7.65(1H，d，J＝5.1Hz)，2.45(2H，t，J＝7.0Hz)，1.65-1.20(4H，m)，0.93(3H，t，J＝7.0Hz)。

Melting point: 86-88 ℃.

(example 40)

N- (4-isobutyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-70)

¹H-NMR(CDCl₃)δ(ppm)：8.91(1H，s)，8.90(1H，d，J＝5.1Hz)，8.71(1H，brd.s)，8.10(1H，s)，7.66(1H，d，J＝5.1Hz)，2.36(2H，d，J＝7.0Hz)，1.95-1.70(1H，m)，0.93(6H，d，J＝7.0Hz)。

Melting point: 81-84 ℃.

(example 41)

N- (4-cyclobutyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-71)

¹H-NMR(CDCl₃)δ(ppm)：9.10-8.60(3H，m)，8.21(1H，s)，7.65(1H，d，J＝5.1Hz)，3.60-3.30(1H，m)，2.45-1.60(6H，m)。

Melting point: 132 ℃ and 135 ℃.

(example 42)

N- (4-cyclopentyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-72)

¹H-NMR(CDCl₃)δ(ppm)：8.93(1H，s)，8.92(1H，d，J＝5.1)，8.39(1H，brd.s)，8.16(1H，s)，7.68(1H，d，J＝5.1Hz)，3.10-2.80(1H，m)，2.20-1.30(8H，m)。

Melting point: 132 ℃ and 133 ℃.

(example 43)

N- (4-hexyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-73)

¹H-NMR(CDCl₃)δ(ppm)：8.91(1H，s)，8.89(1H，d，J＝5.1Hz)，8.12(1H，s)，7.66(1H，d，J＝5.1Hz)，2.45(2H，brd.t，J＝7.0Hz)，1.70-1.15(8H，m)，0.89(3H，t，J＝7.0Hz)。

Melting point: 38-40 ℃.

(example 44)

5- [ N, N-bis (4-trifluoromethylnicotinoyl) ] amino-4-hexylisoxazole (Compound No. 1-74)

¹H-NMR(CDCl₃)δ(ppm)：9.20-8.70(4H，m)，7.95-7.50(3H，m)，2.40-2.00(2H，m)，1.70-1.10(8H，m)，1.00-0.70(3H，m)。

Melting point: 71-74 ℃.

(example 45)

N- (4-benzyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-75)

¹H-NMR(CDCl₃)δ(ppm)：8.77(1H，d，J＝5.1Hz)，8.56(1H，s)，7.95(1H，s)，7.59(1H，d，J＝5.1Hz)，7.40-7.05(5H，m)，3.83(2H，s)。

Physical properties: an oil.

(example 46)

N- (4-phenylethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-76)

¹H-NMR(CDCl₃)δ(ppm)：8.85(1H，d，J＝5.1Hz)，8.76(1H，s)，8.64(1H，brd.s)，7.94(1H，s)，7.63(1H，d，J＝5.1Hz)，7.35-7.05(5H，m)，2.95-2.65(4H，m)。

Physical properties: is amorphous.

(example 47)

N- (4-methoxy-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-77)

¹H-NMR(DMSO-d₆)δ(ppm)：11.32(1H，s)，9.04-9.00(2H，m)，8.85(1H，s)，7.94(1H，d，J＝4.6Hz)，3.82(3H，s)。

Melting point: 123 ℃ and 125 ℃.

(example 48)

N- (4-methoxy-3-methoxymethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-78)

¹H-NMR(CDCl₃)δ(ppm)：8.96-8.94(2H，m)，7.84(1H，brd.s)，7.67(1H，d，J＝4.6Hz)，4.50(2H，s)，3.92(3H，s)，3.41(3H，s)。

Melting point: 144 ℃ and 146 ℃.

(example 49)

N- (4-methylthio-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-79)

¹H-NMR(CDCl₃)δ(ppm)：8.97-8.94(2H，m)，8.25(1H，s)，7.68(1H，d，J＝5.5Hz)，2.32(3H，s)。

Melting point: 127 ℃ and 129 ℃.

(example 50)

5- [ N, N-bis (4-trifluoromethylnicotinoyl) ] amino-4-methylthioisoxazole (Compound No. 1-80)

¹H-NMR(CDCl₃)δ(ppm)：8.93-8.89(4H，m)，8.22(1H，s)，7.65-7.62(2H，m)，2.41(3H，s)。

Physical properties: is amorphous.

(example 51)

N- (4-phenoxy-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-81)

¹H-NMR(CDCl₃)δ(ppm)：8.84(1H，d，J＝5.5Hz)，8.71(1H，s)，8.26(1H，s)，7.59(1H，d，J＝5.5Hz)，7.37-7.26(3H，m)，7.15-7.08(2H，m)，6.99(1H，brd.s)。

Physical properties: an oil.

(example 52)

5- [ N, N-bis (4-trifluoromethylnicotinoyl) ] amino-4-phenoxyisoxazole (Compound No. 1-82)

¹H-NMR(CDCl₃)δ(ppm)：8.91-8.84(4H，m)，8.10(1H，s)，7.62-7.60(2H，m)，7.39-7.31(3H，m)，7.21-7.14(1H，m)，6.99-6.93(2H，m)。

Physical properties: an oil.

(example 53)

N- (4-phenyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-83)

¹H-NMR(CDCl₃)δ(ppm)：8.90-8.87(2H，m)，8.41(1H，s)，8.21(1H，brd.s)，7.63(1H，d，J＝5.1Hz)，7.48-7.36(5H，m)。

Melting point: 152 ℃ and 155 ℃.

(example 54)

N- [4- (4-methylphenyl) -5-isoxazolyl ] -4- (trifluoromethyl) nicotinamide (Compound No. 1-84)

¹H-NMR(CDCl₃)δ(ppm)：8.90-8.88(2H，m)，8.39(1H，s)，7.63(1H，d，J＝4.9Hz)，7.32-7.21(4H，m)，2.37(3H，s)。

Melting point: 155 ℃ and 157 ℃.

(example 55)

N- [4- (4-methoxyphenyl) -5-isoxazolyl ] -4- (trifluoromethyl) nicotinamide (Compound No. 1-85)

¹H-NMR(CDCl₃)δ(ppm)：8.90-8.89(2H，m)，8.44(1H，brd.s)，8.38(1H，s)，7.64(1H，d，J＝5.1Hz)，7.36-7.31(2H，m)，6.99-6.93(2H，m)，3.83(3H，s)。

Melting point: 77-79 ℃.

(example 56)

N- [4- (4-chlorophenyl) -5-isoxazolyl ] -4- (trifluoromethyl) nicotinamide (Compound No. 1-86)

¹H-NMR(CDCl₃)δ(ppm)：8.93-8.91(2H，m)，8.63(1H，brd.s)，8.42(1H，s)，7.65(1H，d，J＝4.9Hz)，7.42-7.26(4H，m)。

Melting point: 166 ℃ and 168 ℃.

Example 57

N- [4- (4-trifluoromethylphenyl) -5-isoxazolyl ] -4- (trifluoromethyl) nicotinamide (Compound No. 1-87)

¹H-NMR(CDCl₃)δ(ppm)：8.95-8.92(2H，m)，8.48(1H，s)，7.71-7.65(3H，m)，7.53(2H，d，J＝8.4Hz)。

Melting point: 128 ℃ and 130 ℃.

(example 58)

N- [4- (4-trifluoromethoxyphenyl) -5-isoxazolyl ] -4- (trifluoromethyl) nicotinamide (Compound No. 1-88)

¹H-NMR(CDCl₃)δ(ppm)：8.93-8.91(2H，m)，8.42(1H，s)，8.27(1H，brd.s)，7.66(1H，d，J＝5.5Hz)，7.46-7.42(2H，m)，7.30-7.26(2H，m)。

Melting point: 161-163 ℃.

(example 59)

N- [4- (3-pyridyl) -5-isoxazolyl ] -4- (trifluoromethyl) nicotinamide (compound No. 1-89)

¹H-NMR(CDCl₃)δ(ppm)：8.93-8.84(2H，m)，8.57-8.56(1H，brd.s)，8.43-8.39(2H，m)，7.76-7.71(1H，m)，7.62-7.60(1H，d，J＝5.2Hz)，7.36-7.31(1H，m)。

Physical properties: is amorphous.

(example 60)

N- (4-chloro-3-methoxyiminomethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-90)

¹H-NMR(CDCl₃)δ(ppm)：8.94-8.88(2H，m)，8.05(1H，s)，7.65(1H，d，J＝5.1Hz)，4.05(3H，s)。

Physical properties: is amorphous.

(example 61)

N- (3-methyl-4-phenyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-91)

¹H-NMR(CDCl₃)δ(ppm)：8.87(1H，d，J＝5.3Hz)，8.78(1H，brds)，8.04(1H，s)，7.60(1H，d，J＝5.3Hz)，7.48-7.30(5H，m)，2.29(3H，s)。

Melting point: 155 ℃ and 157 ℃.

(example 62)

N- [4- (cyclohex-1-en-1-yl) -5-isoxazolyl ] -4- (trifluoromethyl) nicotinamide (Compound No. 1-92)

¹H-NMR(CDCl₃)δ(ppm)：8.92(2H，brd m)，8.20(2H，brd m)，7.65(1H，d，J＝4.6Hz)，5.97-5.94(1H，m)，2.24-2.16(4H，m)，1.76-1.62(4H，m)。

Melting point: 161-163 ℃.

(example 63)

N- (4-methoxymethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-93)

¹H-NMR(CDCl₃)δ(ppm)：8.99-8.95(2H，m)，8.60(1H，s)，8.22(1H，s)，7.68(1H，d，J＝4.9Hz)，4.44(2H，s)，3.40(3H，s)。

Physical properties: is amorphous.

(example 64)

N- [4- (1H-pyrazol-1-yl) -5-isoxazolyl ] -4- (trifluoromethyl) nicotinamide (Compound No. 1-94)

¹H-NMR(CDCl₃)δ(ppm)：10.55(1H，brd s)，9.06-8.06(2H，m)，8.51(1H，s)，7.74-7.65(3H，m)6.48-6.45(1H，m)。

Physical properties: is amorphous.

(example 65)

N- (4-cyclohexyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-95)

¹H-NMR(CDCl₃)δ(ppm)：8.93-8.91(2H，m)，8.22(1H，brd.s)，8.17(1H，s)，7.66(1H，d，J＝5.2Hz)，2.66-2.52(1H，m)，1.91-1.68(4H，m)，1.43-1.22(6H，m)。

Melting point: 125 ℃ and 127 ℃.

(example 66)

N- (4-fluoro-3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide (Compound No. 1-39)

¹H-NMR(DMSO-d₆)δ(ppm)：11.90(1H，s)，9.09(1H，s)，9.03(1H，d，J＝5.1Hz)，7.95(1H，d，J＝5.1Hz)，2.30(3H，s)。

Melting point: 122-124 ℃.

(reference example 1)

3- [ (4, 4, 4-trifluoro-3-oxo-1-butenyl) amino ] -2-propenenitrile (Compounds IIa and IIb, Process D)

Sodium hydride (60% in mineral oil, 400mg, 10mmol) was added to the flask, which was washed 2 times with hexane. N, N-dimethylformamide (10ml) was added to the flask, and a solution of 4-amino-1, 1, 1-trifluoro-3-buten-2-one (1.4g, 10mmol) and 3-methoxyacrylonitrile (830mg, 10mmol) dissolved in N, N-dimethylformamide (5ml) was added dropwise under ice cooling. After stirring at room temperature for 3 hours, the reaction mixture was poured into water (50 ml). The mixture was acidified with concentrated hydrochloric acid under ice cooling, and then extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate 3/1 to 1/1), whereby 993mg (yield 52.3%) of the title compound (IIa) with low polarity and 457mg (yield 24.0%) of the title compound (IIb) with high polarity were obtained.

Low polarity compound (IIa, mixture of 2 geometric isomers) (Rf 0.38; developing solvent: hexane/ethyl acetate 2/1)

¹H-NMR Spectroscopy (200MHz, CD)₃OD)δ(ppm)

Ha：5.90(0.65H，d，J＝13.2Hz)；5.68(0.35H，d，J＝8.1Hz)

Hb：7.93(0.65H，d，J＝13.2Hz)；7.43(0.35H，d，J＝8.1Hz)

Hc：7.53(0.65H，d，J＝13.9Hz)；7.42(0.35H，d，J＝13.9Hz)

Hd：5.44(0.35H，d，J＝13.9Hz)；5.00(0.65H，d，J＝13.9Hz)

MS(EI)：M/Z：190(M⁺)，162，147，133，121。

Highly polar compounds (IIb, mixture of 2 geometric isomers) (Rf 0.16; developing solvent: hexane/ethyl acetate 2/1)

¹H-NMR Spectroscopy (200MHz, CD)₃OD)δ(ppm)

Ha：6.11(0.5H，d，J＝13.2Hz)；5.78(0.5H，d，J＝7.7Hz)

Hb：7.94(0.5H，d，J＝13.2Hz)；7.59(0.5H，d，J＝7.7Hz)

Hc：7.32(0.5H，d，J＝8.4Hz)；7.24(0.5H，d，J＝8.8Hz)

Hd：4.95(0.5H，d，J＝8.4Hz)；4.75(0.5H，d，J＝8.8Hz)

MS(EI)：M/Z：190(M⁺)，151，129，121。

(reference example 2)

Sodium hydride (60% in mineral oil, 400mg, 10mmol) was added to the flask, which was washed 2 times with hexane. To the flask was added 1, 2-dimethoxyethane (20ml), and a solution prepared by dissolving 4-amino-1, 1, 1-trifluoro-3-buten-2-one (1.4g, 10mmol) and 3-methoxyacrylonitrile (830mg, 10mmol) in 1, 2-dimethoxyethane (5ml) was added dropwise under ice-cooling. After stirring at room temperature for 4 hours, the reaction mixture was poured into water (50 ml). The mixture was acidified with concentrated hydrochloric acid under ice cooling, and then extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate 3/1 to 1/1), whereby 593mg (yield 31.2%) of the title compound (IIa) with low polarity and 680mg (yield 35.8%) of the title compound (IIb) with high polarity were obtained.

(reference example 3)

Sodium hydride (60% in mineral oil, 4.00g, 100mmol) was added to the flask and washed 2 times with hexane. N, N-dimethylformamide (100ml) was added thereto, and a solution prepared by dissolving 4-amino-1, 1, 1-trifluoro-3-buten-2-one (13.9g, 100mmol) and 3-methoxyacrylonitrile (8.30g, 100mmol) in N, N-dimethylformamide (50ml) was added dropwise under ice cooling. After stirring at room temperature for 3 hours, the reaction mixture was poured into water (500 ml). The mixture was acidified with concentrated hydrochloric acid under ice cooling, and then the precipitate was filtered off and washed with cold water, and the resulting crystals were dried under reduced pressure to obtain 8.20g (yield 43.1%) of compounds (IIa) and (IIb) as a mixture.

(reference example 4)

3- [ (4, 4, 4-trifluoro-3-oxo-1-butenyl) amino ] -2-propenenitrile (Compounds IIa and IIb, procedure E)

Sodium hydride (60% in mineral oil, 400mg, 10mmol) was added to the flask, which was washed 2 times with hexane. N, N-dimethylformamide (15ml) was added thereto, and a solution prepared by dissolving 4-amino-1, 1, 1-trifluoro-3-buten-2-one (1.4g, 10mmol) and 3, 3-dimethoxypropionitrile (1.15g, 10mmol) in N, N-dimethylformamide (5ml) was added dropwise under ice cooling. After stirring at room temperature for 4 hours, the reaction mixture was poured into water (50 ml). The mixture was acidified with concentrated hydrochloric acid and extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate 3/1 to 1/1), whereby 251mg (yield 13.2%) of the title compound (IIa) with low polarity and 372mg (yield 19.8%) of the title compound (IIb) with high polarity were obtained.

(reference example 5)

3-cyano-4-trifluoromethylpyridine (Compound VIIb, Process F)

To 28% sodium methoxide (580mg, 3.0mmol) was added a solution of 3- [ (4, 4, 4-trifluoro-3-oxo-1-butenyl) amino ] -2-acrylonitrile (mixture of IIa and IIb; 380mg, 2.0mmol) dissolved in methanol (5ml) at room temperature, followed by reflux for 2 hours. The reaction solution was poured into water, and extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over magnesium sulfate, and concentrated. The obtained residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate 3/1) to obtain the title compound (195 mg, 56.5% yield).

¹H-NMR Spectroscopy (200MHz, CD)₃OD)δ(ppm)9.11(1H，s)，9.03(1H，d，J＝5.1Hz)，7.72(1H，d，J＝5.1Hz)。

(reference example 6)

3-cyano-4-trifluoromethylpyridine (Compound VIIb, Process F)

To 28% sodium methoxide (290mg, 1.5mmol) was added a solution of 3- [ (4, 4, 4-trifluoro-3-oxo-1-butenyl) amino ] -2-acrylonitrile (less polar compound IIa; 190mg, 1.0mmol) dissolved in methanol (2ml) at room temperature, followed by reflux for 2 hours. The reaction solution was poured into water, and extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over magnesium sulfate, and concentrated. The obtained residue was purified by thin layer chromatography (developing solvent: hexane/ethyl acetate 3/1) to obtain the title compound 71.0mg (yield 41.5%).

(reference example 7)

3-cyano-4-trifluoromethylpyridine (Compound VIIb, Process F)

To 28% sodium methoxide (290mg, 1.5mmol) was added a solution of 3- [ (4, 4, 4-trifluoro-3-oxo-1-butenyl) amino ] -2-acrylonitrile (highly polar compound IIb; 190mg, 1.0mmol) dissolved in methanol (2ml) at room temperature, followed by reflux for 2 hours. The reaction solution was poured into water, and extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over magnesium sulfate, and concentrated. The obtained residue was purified by thin layer chromatography (developing solvent: hexane/ethyl acetate 3/1) to obtain the title compound 81.0mg (yield 47.2%).

(reference example 8)

4-Trifluoromethylnicotinamide (Compound VIIc, Process F)

3- [ (4, 4, 4-trifluoro-3-oxo-1-butenyl) amino ] -2-acrylonitrile (a mixture of IIa and IIb; 1.90g, 10mmol) was dissolved in methanol (15ml), and sodium hydroxide (600mg, 15mmol) was added thereto, followed by heating and refluxing for 6 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (developing solvent: hexane/acetone-1/1) to obtain 1.25g of the title compound (yield 65.6%).

¹H-NMR spectra (200MHz, DMSO-d)₆)δ(ppm)8.89(1H，d，J＝5.1Hz)，8.82(1H，s)，8.18(1H，brs)，7.85(1H，brs)，7.81(1H，d，J＝5.1Hz)。

(reference example 9)

4-Trifluoromethylnicotinamide (Compound VIIc, Process F)

3- [ (4, 4, 4-trifluoro-3-oxo-1-butenyl) amino ] -2-acrylonitrile (low-polarity compound IIa; 1.90g, 10mmol) was dissolved in methanol (15ml), and sodium hydroxide (600mg, 15mmol) was added thereto, followed by heating and refluxing for 6 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (developing solvent: hexane/acetone-1/1) to obtain 1.25g of the title compound (yield 65.6%).

(reference example 10)

4-Trifluoromethylnicotinamide (Compound VIIc, Process F)

3- [ (4, 4, 4-trifluoro-3-oxo-1-butenyl) amino ] -2-acrylonitrile (highly polar compound IIb; 2.10g, 11mmol) was dissolved in methanol (15ml), and sodium hydroxide (680mg, 17mmol) was added thereto, followed by heating and refluxing for 6 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (developing solvent: hexane/acetone-1/1) to obtain 1.26g of the title compound (yield 60.1%).

(reference example 11)

4-Trifluoromethylnicotinamide (Compound VIIc, Process F)

3- [ (4, 4, 4-trifluoro-3-oxo-1-butenyl) amino ] -2-acrylonitrile (a mixture of IIa and IIb; 1.90g, 10mmol) was dissolved in ethanol (15ml), and sodium hydroxide (600mg, 17mmol) was added thereto, followed by heating and refluxing for 8 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (developing solvent: hexane/acetone-1/1) to obtain 0.53g of the title compound (yield 26.5%).

(reference example 12)

4-Trifluoromethylnicotinamide (Compound VIIc, Process F)

3- [ (4, 4, 4-trifluoro-3-oxo-1-butenyl) amino ] -2-acrylonitrile (a mixture of IIa and IIb; 1.90g, 10mmol) was dissolved in methanol (15ml), and potassium hydroxide (990mg, 15mmol) was added thereto, followed by heating and refluxing for 6 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (developing solvent: hexane/acetone-1/1) to obtain 1.03g of the title compound (yield 52.6%).

(reference example 13)

3-cyano-4-trifluoromethylpyridine (Compound VIIb, Process F)

3- [ (4, 4, 4-trifluoro-3-oxo-1-butenyl) amino ] -2-acrylonitrile (a mixture of IIa and IIb; 1.90g, 10mmol) was dissolved in methanol (20ml), potassium carbonate (2.10g, 15mmol) was added, and the mixture was refluxed for 2 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate 3/1) to give the title compound 653mg (yield 32.7%).

(reference example 14)

4-Trifluoromethylnicotinic acid (Compound VIII)

To 4-trifluoromethylnicotinamide (90g, 10mmol), 5ml of 35% concentrated hydrochloric acid (10ml, 57mmol) was added, and the mixture was refluxed for 5 hours. Water (50ml) was added to the reaction solution, which was adjusted to pH 3 with sodium carbonate, and then extracted with ethyl acetate 2 times. The organic layers were combined, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 1.71g of the title compound (yield 89.7%).

¹H-NMR spectra (500MHz, DMSO-d)₆)δ(ppm)14.07(1H，brd.s)，9.08(1H，s)，9.00(1H，d，J＝5.2Hz)，7.89(1H，d，J＝5.2Hz)。

(reference example 15)

4-Trifluoromethylnicotinic acid (Compound VIII)

3-cyano-4-trifluoromethylpyridine (11.47g, 66.64mmol) was suspended in ethylene glycol (76ml), 85% potassium hydroxide (13.20g, 200mol) was added, and the mixture was stirred with heating at 20 ℃ for 4 hours. After the reaction mixture was allowed to cool to room temperature, water (50ml) and 4N hydrochloric acid (60ml) were added, and the mixture was extracted 4 times with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 10.70g of the title compound (yield 84.0%).

(reference example 16)

4-Trifluoromethylnicotinic acid (Compound VIII)

To a suspension of sodium hydride (60% in mineral oil, 0.40g, 10mmol) in tetrahydrofuran 10ml was slowly added a solution of 4-amino-1, 1, 1-trifluoromethyl-3-buten-2-one (1.39g, 10mmol) and 3-methoxyacrylonitrile (0.83g, 10mmol) in tetrahydrofuran (2ml) under ice-cooling. After stirring at the same temperature for 20 minutes, further stirring was carried out at room temperature for 3 hours. After concentrated hydrochloric acid (1.2ml) was added to the reaction mixture, the solvent was distilled off under reduced pressure. To the obtained residue was added ethyl acetate, and the organic layer was washed with saturated brine 2 times, dried over magnesium sulfate, and concentrated. The residue was dissolved in methanol (20ml), and 28% sodium methoxide (1.93g, 10.0mmol) was added thereto, followed by refluxing for 3 hours. After methanol was distilled off from the reaction mixture under reduced pressure, 8 equivalents of an aqueous sodium hydroxide solution (5ml, 40.0mmol) was added, and the mixture was refluxed for 5 hours. The reaction mixture was poured into water, and the aqueous layer was washed with diethyl ether. The aqueous layer was acidified with concentrated hydrochloric acid and extracted 2 times with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 866mg of the title compound (yield 45.3%).

(reference example 17)

4- (trifluoromethyl) nicotinoyl chloride (Compound VIII)

4- (trifluoromethyl) nicotinic acid (50.09G, 0.262mol) was suspended in benzene (250ml), and thionyl chloride (38.2ml, 0.524mol) and N, N-dimethylformamide (0.1ml) were added to the suspension and refluxed for 3 hours. The reaction solution was concentrated, and the residue was distilled under reduced pressure to give 49.45g of the title compound (yield 90.1%).

¹H-NMR Spectroscopy (270MHz, CDCl)₃)δ(ppm)9.32(1H，s)，9.03(1H，d，J＝5.2Hz)，7.71(1H，d，J＝5.2Hz)。

(reference example 18)

Sodium hydride (60% in mineral oil, 0.6g, 15mmol) was added to the flask and washed 2 times with hexane. 1, 3-dimethyl-2-imidazolidinone (20ml) was added thereto, and a solution prepared by dissolving 4-amino-1, 1, 1-trifluoro-3-buten-2-one (2.1g, 15mmol) and 3-methoxyacrylonitrile (1.2g, 15mmol) in 1, 3-dimethyl-2-imidazolidinone (5ml) was added dropwise under ice cooling. After stirring at room temperature for 3 hours, the reaction mixture was poured into water (200 ml). The mixture was acidified with concentrated hydrochloric acid under ice cooling, and then extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate 3/1 to 2/1) to obtain the title compounds (IIa) and (IIb)2.60G as a mixture (yield 92.0%).

(reference example 19)

4-Trifluoromethylnicotinic acid (Compound VIII)

To a 28% solution of sodium methoxide (193.0g, 1.00mol) in methanol (1.0L) was added 4-amino-1, 1, 1-trifluoro-3-buten-2-one (159.6g, 0.84mmol), and the mixture was refluxed for 3 hours. After methanol was distilled off from the reaction mixture under reduced pressure, 8mol/L aqueous sodium hydroxide solution (420ml, 3.36mol) was added thereto and refluxed for 4 hours. The reaction mixture was poured into water, and the aqueous layer was washed with diethyl ether. The aqueous layer was acidified with concentrated hydrochloric acid and extracted 2 times with ethyl acetate. The obtained organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to obtain 112.8g of the title compound (yield 70.4%).

In the following formulation examples, the kinds and the blending ratio of the compound and the auxiliary are not limited and can be changed in a wide range. In the following description,% represents a mass percentage.

(preparation example 1) emulsion

To the compound (5%) of example 6, xylene (42.5%) and dimethyl sulfoxide (42.5%) were added and dissolved, and then a mixture of polyoxyethylene castor oil ether and calcium alkylbenzenesulfonate (mixing ratio: 8/2.10%) was mixed to prepare an emulsion. The present agent was diluted with water and used as a dispersion.

(formulation example 2) wettable powder

To the compound (5%) of example 6, kaolin (79%) and diatomaceous earth (10%) were mixed, and sodium lauryl sulfate (3%) and sodium lignosulfonate (3%) were further mixed, followed by micro-pulverization to obtain a wettable powder. The present agent was diluted with water and used as a dispersion.

(formulation example 3) powder preparation

A mixture of talc and calcium carbonate (mixing ratio: 1/1.99%) was added to the compound (1%) of example 6, and after mixing, the mixture was pulverized to prepare a powder. The agent is directly spread and used.

(preparation example 4) granules

The compound (2%) of example 6 was mixed with fine bentonite powder (30%), talc (66%) and sodium lignosulfonate (2%), and then water was added thereto and kneaded until uniform. Then, the granules are granulated by a granulator, and then passed through a granulator, a dryer and a screen to prepare granules having a particle size of 0.6 to 1.0 mm. The agent is directly spread on the soil surface for use.

(preparation example 5) oil preparation

The compound (0.1%) of example 6 was dissolved in white kerosene to make the total amount 100%, to obtain an oil agent.

Test example 1 insecticidal test for Myzus persicae (100ppm)

Water (30ml) was added to the beaker, and 1 piece of rape leaves was stood in the beaker so that the petioles were immersed in the water. 5 myzus persicae were bred on the back of the leaf of rape to make the myzus persicae fart. After 2 days of stocking, adult insects were removed and the number of larvae was counted.

Surfactant ニユ - コ - ル N E-710F (registered trademark, manufactured by Nippon emulsifier Co., Ltd.; 2%) was dissolved in aqueous acetone (aqueous 95%. 98%) to obtain solution 1. Next, dispersant ゴ - セノ - ル GLO5-S (registered trademark, 0.2% aqueous solution, 0.2%) was dissolved in water (99.8%) to obtain solution 2.

To a compound of the present invention (8mg) were added the above-mentioned solution 1(0.4ml), the above-mentioned solution 2(0.4ml) and water (8ml), and further, the compound of the present invention was diluted with water to 100ppm { 0.01% of グラミン S (registered trademark, manufactured by Sanko Co., Ltd.) as a developing solvent was added }.

The above chemical solution (8ml) was spread on the rape leaves using a rotary spreading tower. Rape leaves were placed back in the beaker and placed at 25 ℃ for 16 hours: bright, 8 hours: in a dark thermostated chamber. And (5) inspecting the number of dead insects after 5 days of spreading, and calculating the dead insect rate.

As a result, examples 1 (Compound No. 1-2), 2 (Compound No. 1-51), 3 (Compound No. 1-21), 4 (Compound No. 1-1), 5 (Compound No. 1-3), 6 (Compound No. 1-5), 7 (Compound No. 1-16), 8 (Compound No. 1-17), 9 (Compound No. 1-18), 10 (Compound No. 1-19), 11 (Compound No. 1-20), 12 (Compound No. 1-25), 13 (Compound No. 1-37), 14 (Compound No. 1-41), 15 (Compound No. 1-43), Example 16 (Compound Nos. 1 to 47), example 18 (Compound Nos. 1 to 49), example 19 (Compound Nos. 1 to 53), example 20 (Compound Nos. 1 to 55), example 21 (Compound No. 2 to 2), example 22 (Compound Nos. 1 to 36), example 23 (Compound Nos. 1 to 38), example 24 (Compound Nos. 1 to 40), example 25 (Compound Nos. 1 to 42), example 26 (Compound Nos. 1 to 56), example 27 (Compound Nos. 1 to 57), example 28 (Compound Nos. 1 to 58), example 29 (Compound Nos. 1 to 59), example 30 (Compound Nos. 1 to 60), example 31 (Compound Nos. 1 to 61), example 32 (Compound Nos. 1 to 62), Example 33 (Compound Nos. 1 to 63), example 34 (Compound Nos. 1 to 64), example 35 (Compound Nos. 1 to 65), example 36 (Compound Nos. 1 to 66), example 37 (Compound Nos. 1 to 67), example 38 (Compound Nos. 1 to 68), example 39 (Compound Nos. 1 to 69), example 40 (Compound Nos. 1 to 70), example 41 (Compound Nos. 1 to 71), example 42 (Compound Nos. 1 to 72), example 43 (Compound Nos. 1 to 73), example 44 (Compound Nos. 1 to 74), example 45 (Compound Nos. 1 to 75), example 46 (Compound Nos. 1 to 76), example 47 (Compound Nos. 1 to 77), example 48 (Compound Nos. 1 to 78), Example 49 (Compound Nos. 1 to 79), example 50 (Compound Nos. 1 to 80), example 51 (Compound Nos. 1 to 81), example 52 (Compound Nos. 1 to 82), example 53 (Compound Nos. 1 to 83), example 54 (Compound Nos. 1 to 84), example 55 (Compound Nos. 1 to 85), example 56 (Compound Nos. 1 to 86), example 57 (Compound Nos. 1 to 87), example 58 (Compound Nos. 1 to 88), example 59 (Compound Nos. 1 to 89), example 60 (Compound Nos. 1 to 90), example 61 (Compound Nos. 1 to 91), example 62 (Compound Nos. 1 to 92), example 63 (Compound Nos. 1 to 93), example 64 (Compound Nos. 1 to 94), The compounds of example 65 (compound numbers 1 to 95) and example 66 (compound numbers 1 to 39) showed a mortality of 95% or more.

(test example 2) insecticidal test on Myzus persicae (10ppm and 3ppm)

The test was carried out in the same manner as in test example 1 except that the diluted concentrations were 10ppm and 3 ppm. For comparison, the comparative compound a and the comparative compound b (Compound No. 6) described in Table 1 of JP-A-10-195072 were used.

Comparative Compound a comparative Compound b

Example 1 example 4

Compound No. 1-2 Compound No. 1-1

The results are shown in Table 3.

(Table 3)

Insecticidal test for myzus persicae

Industrial applicability

The N-heteroaryl-4- (haloalkyl) nicotinamide derivatives of the present invention exhibit excellent control effects against a wide range of pests such as hemiptera pests, lepidoptera pests, coleopteran pests, dipteran pests, hymenopteran pests, orthopteran pests, isopteran pests, thysanopteran pests, phyllodes pests, plant-parasitic nematodes and the like.

Further, according to the present invention, the compound (II) which is a production intermediate useful as a compound which can be used as a raw material for producing an agricultural chemical or a pharmaceutical can be produced at a high yield and at low cost and easily.

Claims

1. An N-heteroaryl-4- (haloalkyl) nicotinamide derivative represented by the following general formula (I) or a salt thereof

Wherein R represents C which is substituted or unsubstituted with a halogen atom₁～C₆An alkyl group;

R¹represents a hydrogen atom, is substituted by a substituent selected from the following substituent group A orUnsubstituted C₁～C₆Alkyl radical, C₂～C₆Alkenyl or 4-trifluoromethyl nicotinoyl;

R²and R³Each independently represents a hydrogen atom, a halogen atom,

Is driven from C₁～C₆C substituted or unsubstituted by a substituent selected from alkoxy and phenyl₁～C₆Alkyl radical, C₃～C₇Cycloalkyl radical, C₂～C₆An alkenyl group,

Formyl, methyl,

By the formula CH-NOR⁴A group represented by (I), wherein R⁴Is a hydrogen atom or C₁～C₆An alkyl group, a carboxyl group,

a cyano group,

Phenyl, pyrazolyl, pyridyl, C substituted or unsubstituted by a substituent selected from the following substituent group B₁～C₆Alkoxy radical, C₁～C₆Alkylthio or phenoxy;

substituent group A is represented by C₁～C₆Alkoxy radical, C₁～C₆Alkylthio and cyano; and

substituent group B is C substituted or unsubstituted with halogen atom₁～C₆Alkyl, C substituted or unsubstituted by halogen atoms₁～C₆Alkoxy and cyano.

2. The N-heteroaryl-4- (haloalkyl) nicotinamide derivative or salt thereof as claimed in claim 1, wherein R¹Is a hydrogen atom.

3. The N-heteroaryl-4- (haloalkyl) nicotinamide derivative of claim 1, or a salt thereof, wherein X is represented by the formula C-R²The group shown.

4. The N-heteroaryl-4- (haloalkyl) nicotinamide derivative as claimed in claim 3An organism or a salt thereof, wherein R²Is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, an iodine atom,

Is driven from C₁～C₄C unsubstituted or substituted by a substituent selected from the group consisting of alkoxy and phenyl₁～C₄Alkyl radical, C₃～C₆Cycloalkyl radical, C₂～C₄An alkenyl group,

C substituted or unsubstituted by fluorine, chlorine, fluorine or chlorine atoms₁～C₄Alkyl, C substituted or unsubstituted by fluorine or chlorine atoms₁～C₄Phenyl which is substituted or unsubstituted with a substituent selected from the group consisting of alkoxy and cyano,

C substituted or unsubstituted by fluorine, chlorine, fluorine or chlorine atoms₁～C₄Alkyl, C substituted or unsubstituted by fluorine or chlorine atoms₁～C₄Pyrazolyl, pyridyl, unsubstituted or substituted by a substituent selected from the group consisting of alkoxy and cyano,

Is selected from fluorine atom, chlorine atom and C₁～C₄C unsubstituted or substituted by a substituent selected from the group consisting of alkoxy₁～C₄Alkoxy radical, C₁～C₄Alkylthio, or

C substituted or unsubstituted by fluorine, chlorine, fluorine or chlorine atoms₁～C₄Alkyl, C substituted or unsubstituted by fluorine or chlorine atoms₁～C₄A substituted phenoxy group selected from the group consisting of alkoxy and cyano.

5. The N-heteroaryl-4- (haloalkyl) nicotinamide derivative or salt thereof as claimed in claim 1, wherein R²Is hydrogen atom, fluorine atom, chlorine atom, bromine atom, iodine atom, or C₁～C₃Alkoxy substituted or unsubstituted C₁～C₃Alkyl radical, C₃～C₅Cycloalkyl radical, C₃～C₄An alkenyl group,

C substituted or unsubstituted by fluorine atom, chlorine atom, or by fluorine atom₁～C₃Alkyl, C substituted or unsubstituted by fluorine atoms₁～C₃Phenyl which is substituted or unsubstituted with a substituent selected from the group consisting of alkoxy and cyano,

Is selected from fluorine atom, chlorine atom and C₁～C₃A pyridyl group substituted or unsubstituted with a substituent selected from the group consisting of alkyl groups,

Is selected from fluorine atom, chlorine atom and C₁～C₃A pyrazolyl group which is substituted or unsubstituted with a substituent selected from the group consisting of alkyl groups,

C substituted or unsubstituted by fluorine atoms₁～C₃Alkoxy radical, C₁～C₃Alkylthio, or

C substituted or unsubstituted by fluorine atom, chlorine atom, or by fluorine atom₁～C₃Alkyl, C substituted or unsubstituted by fluorine atoms₁～C₃A substituted or unsubstituted phenoxy group with a substituent selected from the group consisting of alkoxy and cyano.

6. The N-heteroaryl-4- (haloalkyl) nicotinamide derivative or salt thereof as claimed in claim 3, wherein R²Is hydrogen atom, fluorine atom, chlorine atom, bromine atom, C₁～C₃Alkyl, cyclopropyl, allyl, phenyl, pyridyl, pyrazolyl, C₁～C₂Alkoxy radical, C₁～C₂Alkylthio or phenoxy.

7. The N-heteroaryl-4- (haloalkyl) nicotinamide derivative or salt thereof as claimed in claim 3, wherein R²Is hydrogen atom, chlorine atom, bromine atom, methyl, ethyl or methoxyl.

8. The N-heteroaryl-4- (haloalkyl) nicotinamide derivative or a salt thereof according to any one of claims 1 to 7, wherein R³Is hydrogen atom, fluorine atom, chlorine atom, bromine atom, or C₁～C₄Alkoxy substituted or unsubstituted C₁～C₄Alkyl radical, C₃～C₆Cycloalkyl, formyl, and,

By the formula CH-NOR^4aA group represented by (I), wherein R^4aIs a hydrogen atom or C₁～C₄An alkyl group, a carboxyl group,

cyano radicals, or

C substituted or unsubstituted by fluorine, chlorine, bromine, fluorine or chlorine₁～C₄Alkyl radical, C₁～C₄And phenyl which is substituted or unsubstituted with 1 to 3 substituents which are the same or different and are selected from the group consisting of alkoxy and cyano.

9. The N-heteroaryl-4- (haloalkyl) nicotinamide derivative or a salt thereof according to any one of claims 1 to 7, wherein R³Is a hydrogen atom, a fluorine atom, a chlorine atom,

Quilt C₁～C₂Alkoxy substituted or unsubstituted C₁～C₂Alkyl radical, C₃～C₅Cycloalkyl, or

C substituted or unsubstituted by fluorine atom, chlorine atom, or by fluorine atom₁～C₂Alkyl radical, C₁～C₂And a phenyl group which is unsubstituted or substituted by 1 to 3 substituents which are the same or different and selected from the group consisting of an alkoxy group and a cyano group.

10. The N-heteroaryl-4- (haloalkyl) nicotinamide derivative or a salt thereof according to any one of claims 1 to 7, wherein R³Hydrogen atom, chlorine atom, methyl, methoxymethyl, cyclopropyl or phenyl.

11. The N-heteroaryl-4- (haloalkyl) nicotinamide derivative or a salt thereof according to any one of claims 1 to 7, wherein R³Is a hydrogen atom or a methyl group.

12. An N-heteroaryl-4- (haloalkyl) nicotinamide derivative or salt thereof as claimed in any of claims 1 to 7, selected from the group consisting of:

n- (5-isoxazolyl) -4- (trifluoromethyl) nicotinamide,

N- (3-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide,

N- (4-chloro-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide,

N- (4-bromo-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide,

N- (4-methyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide,

N- (4-ethyl-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide, and

n- (4-methoxy-5-isoxazolyl) -4- (trifluoromethyl) nicotinamide.

13. A pesticide comprising the N-heteroaryl-4- (haloalkyl) nicotinamide derivative or a salt thereof according to any one of claims 1 to 12 as an active ingredient.

14. A process for producing an N-heteroaryl-4- (haloalkyl) nicotinamide derivative or a salt thereof according to claim 1, which comprises reacting a compound represented by the general formula (IV)

Wherein R represents C which is substituted or unsubstituted with a halogen atom₁～C₆An amine compound represented by an alkyl group and a compound represented by the general formula (V)

X^a-CH＝CH-CN (V)

In the formula, X^aRepresents a leaving group

An acrylonitrile compound represented by the general formula (VI)

(R^aO)₂CH-CH₂-CN (VI)

In the formula, R^aRepresents a hydrogen atom or C₁～C₆Alkyl radical

Reaction of a propionitrile compound represented by the general formula (II)

Wherein R represents the same definition as above

Wherein R represents the same definition as above, A represents a cyano group, a carbamoyl group or a 4-substituted pyridine compound having a cyano group, a carbamoyl group or a carboxyl group at the 3-position represented by a carboxyl group, and if necessary, an acid or a base may be added to the 4-substituted pyridine compound to conduct hydrolysis, thereby preparing a compound represented by the general formula (VIII)

Wherein R represents the same definition as above

Wherein R represents the same definition as above, and X^bAn acid halide compound represented by a chlorine atom or a bromine atom, and then reacting the acid halide compound with a compound represented by the general formula (III)

In the formula (I), the compound is shown in the specification,R¹c represents a hydrogen atom, substituted or unsubstituted with a substituent selected from the following substituent group A₁～C₆Alkyl radical, C₂～C₆Alkenyl or 4-trifluoromethyl nicotinoyl;

R²and R³Each independently represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl group₁～C₆C substituted or unsubstituted by a substituent selected from alkoxy and phenyl₁～C₆Alkyl radical, C₃～C₇Cycloalkyl radical, C₂～C₆Alkenyl, formyl, and,

cyano, phenyl which is substituted or unsubstituted by a substituent selected from the following substituent group B, pyrazolyl, pyridyl, C₁～C₆Alkoxy radical, C₁～C₆Alkylthio or phenoxy;

substituent group B is C substituted or unsubstituted with halogen atom₁～C₆Alkyl, C substituted or unsubstituted by halogen atoms₁～C₆Alkoxy and cyano; the N-heteroaryl-4- (haloalkyl) nicotinamide derivative represented by the general formula (I) or a salt thereof can be produced by reacting the amino compound represented by the general formula (I) with an optionally alkylated, alkenylated or acylated compound

In the formula, R, X, R¹And R³The same definitions as above are indicated.

15. A process for producing an N-heteroaryl-4- (haloalkyl) nicotinamide derivative or a salt thereof according to claim 1, which comprises reacting a compound represented by the general formula (IX)

Wherein R represents the same definition as above, and X^bAn acid halide compound represented by a chlorine atom or a bromine atom and a compound represented by the general formula (III)

In the formula, R¹C represents a hydrogen atom, substituted or unsubstituted with a substituent selected from the following substituent group A₁～C₆Alkyl radical, C₂～C₆Alkenyl or 4-trifluoromethyl nicotinoyl;

substituent group B is C substituted or unsubstituted with halogen atom₁～C₆Alkyl radicals, taken by halogen atomsSubstituted or unsubstituted C₁～C₆Alkoxy and cyano; the N-heteroaryl-4- (haloalkyl) nicotinamide derivative represented by the general formula (I) or a salt thereof can be produced by reacting the amino compound represented by the general formula (I) with an optionally alkylated, alkenylated or acylated compound

In the formula, R, X, R¹And R³The same definitions as above are indicated.