WO2012161133A1 - Composé pyridazine substitué et agent bactéricide agricole ou horticole - Google Patents

Composé pyridazine substitué et agent bactéricide agricole ou horticole Download PDF

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WO2012161133A1
WO2012161133A1 PCT/JP2012/062851 JP2012062851W WO2012161133A1 WO 2012161133 A1 WO2012161133 A1 WO 2012161133A1 JP 2012062851 W JP2012062851 W JP 2012062851W WO 2012161133 A1 WO2012161133 A1 WO 2012161133A1
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group
halo
alkyl
alkyl group
optionally substituted
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PCT/JP2012/062851
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Japanese (ja)
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西尾　晃一
誠 稲田
基浩 梶
大智 下宮
陽介 中山
秀仁 桑原
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日産化学工業株式会社
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Priority to JP2013516352A priority Critical patent/JPWO2012161133A1/ja
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/58—1,2-Diazines; Hydrogenated 1,2-diazines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A61P33/12—Schistosomicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings

Definitions

  • the present invention relates to a novel substituted pyridazine compound and a salt thereof, and a fungicide containing at least one selected from the substituted pyridazine compound and a salt thereof as an active ingredient, particularly an agricultural and horticultural fungicide.
  • the agrochemical in the present invention means an insecticide / acaricide, nematicide, herbicide, fungicide, etc. in the field of agriculture and horticulture.
  • Patent Document 1 and Non-Patent Document 1 disclose certain types of substituted pyridazine compounds, but do not disclose any substituted pyridazine compounds according to the present invention. Further, its usefulness as a bactericidal agent, particularly as an agricultural or horticultural bactericidal agent, is not known at all.
  • a novel substituted pyridazine compound represented by the following general formula (1) is a fungicide, particularly an agricultural and horticultural fungicide. It has been found to be an extremely useful compound that has excellent control activity and high safety against target crops, and has almost no adverse effect on non-target organisms such as mammals, fish and beneficial insects. Completed the invention.
  • Het represents a pyridine ring represented by any of D1-1 to D1-3, R 1 and R 2 each independently represent a ring represented by any one of G-1 to G-5; R 3 represents a hydrogen atom, a hydroxy group, a mercapto group, a halogen atom, a cyano group, a formyl group, a carboxyl group, a C 1 -C 6 alkyl group, a C 2 -C 6 alkenyl group, a C 2 -C 6 alkynyl group, a halo (C 1 -C 6 ) alkyl group, halo (C 2 -C 6 ) alkenyl group, halo (C 2 -C 6 ) alkynyl group, C 1 -C 6 alkoxy group, halo (C 1 -C 6 ) alkoxy group C 2 -C
  • R d2 and R e2 are each independently a C 1 -C 4 alkyl group, a (C 1 -C 4 ) alkyl group optionally substituted with R f , a halo (C 1 -C 4 ) alkyl group, C 2 ⁇ C 5 alkenyl group, optionally substituted by R f (C 2 ⁇ C 5 ) alkenyl group, C 2 ⁇ C 5 alkynyl group, optionally substituted by R f (C 2 ⁇ C 5 ) alkynyl group, A C 1 -C 4 alkylsulfonyl group, —C (O) R i , —C (O) OR i , —CH ⁇ N—OR i , a phenyl group or a phenyl (C 1 -C 2 ) alkyl group, Alternatively, R d2 and R e2 together may represent a C 2 -C 7
  • R f is a hydroxy group, mercapto group, cyano group, nitro group, formyl group, carboxyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, C 1- C 6 alkylsulfonyl group, tri (C 1 -C 6 ) alkylsilyl group, phenyl group, —NH 2 , —NHR g , —N (R h ) R g , —C (O) R i , —C (S ) R i , —C (O) OR i , —C (O) SR i , —C (O) NH 2 , —C (S) NH 2 , —C (O) NHR g , —C (S) NHR g , -C (O) N (
  • the alkylene chain may be interrupted by an oxygen atom, a sulfur atom or NH
  • R i is a C 1 -C 4 alkyl group, C 2 -C 5 alkenyl group, C 2 -C 5 alkynyl group, halo (C 1 -C 4 ) alkyl group, phenyl group or phenyl (C 1 -C 2 )
  • m represents an integer of 1 to 4
  • n represents an integer of 0 to 1
  • p represents an integer of 0 to 5
  • q represents an integer of 0 to 4
  • r represents an integer of 0 to 3
  • s represents an integer of 0 to 2
  • each p, q, r and s may be the same or different from each other.
  • R 3 represents a hydrogen atom, a hydroxy group, a mercapto group, a halogen atom, a cyano group, C 1 ⁇ C 6 alkyl group, C 2 ⁇ C 6 alkenyl group, C 2 ⁇ C 6 alkynyl group, halo (C 1 ⁇ C 6 ) Alkyl group, C 1 -C 6 alkoxy group, halo (C 1 -C 6 ) alkoxy group, C 2 -C 6 alkenyloxy group, C 2 -C 6 alkynyloxy group, C 1 -C 6 alkylthio group, halo (C 1 -C 6 ) alkylthio group, C 1 -C 6 alkylsulfinyl group, halo (C 1 -C 6 ) alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, halo (C 1 -C 6 ) alkylsulf
  • R 3 represents a hydrogen atom, a hydroxy group, a halogen atom, a cyano group, a C 1 -C 6 alkyl group, a halo (C 1 -C 6 ) alkyl group, a C 1 -C 6 alkoxy group, a halo (C 1 -C 6 ) Represents an alkoxy group, a C 1 -C 6 alkylthio group, a C 1 -C 6 alkylsulfinyl group, a C 1 -C 6 alkylsulfonyl group, —C (O) NH 2 or —C (S) NH 2 ;
  • R a and R b are each independently a hydroxy group, a halogen atom, a nitro group, a cyano group, a C 1 -C 6 alkyl group, a (C 1 -C 6 ) alkyl group optionally substituted with R f , a halo
  • R 3 represents a hydrogen atom, a halogen atom, a cyano group, a C 1 to C 6 alkyl group, a halo (C 1 to C 6 ) alkyl group, a C 1 to C 6 alkoxy group, or a halo (C 1 to C 6 ) alkoxy group.
  • R 1 and R 2 each independently represent G-1, G-2, G-4 or G-5;
  • R 3 is a hydrogen atom, a halogen atom, a cyano group, a C 1 -C 6 alkyl group, a C 1 -C 6 alkoxy group, a C 1 -C 6 alkylthio group, a C 1 -C 6 alkylsulfinyl group, or a C 1 -C 6 represents an alkylsulfonyl group, —C (O) NH 2 or —C (S) NH 2 ;
  • R a and R b are each independently a hydroxy group, a halogen atom, a nitro group, a cyano group, a C 1 -C 6 alkyl group, a (C 1 -C 6 ) alkyl group optionally substituted with R f , a halo (C 1 -C 6 ) alkyl group, C 1 -C 6 alkoxy
  • R f is a cyano group, a C 1 -C 6 alkoxy group, a C 1 -C 6 alkylthio group, a tri (C 1 -C 6 ) alkylsilyl group, a phenyl group, —N (R h ) R g , —C ( O) R i , —C (O) OR i or oxiran-2-yl, R g and R h each independently represents a C 1 -C 4 alkyl group, R i represents a substituted pyridazine compound or a salt thereof according to the above [4], wherein R 1 represents a C 1 -C 4 alkyl group or a phenyl group.
  • R 1 represents G-1, G-2-1, G-4-1 or G-5-1
  • R 2 represents G-1 or G-4-1
  • each R b may be the same or different from each other, and the substituted pyridazine compound or a salt thereof according to the above [5].
  • Het represents D1-1, R 1 and R 2 are substituted pyridazine compounds or salts thereof according to the above [6], wherein G-1 is G-1.
  • Het represents D1-1, R 1 represents G-2-1; R 2 represents the substituted pyridazine compound or a salt thereof according to the above [6], wherein G-1 is represented.
  • An antifungal agent comprising, as an active ingredient, one or more selected from the substituted pyridazine compounds according to the above [1] to [8] and salts thereof.
  • An endoparasite control agent comprising, as an active ingredient, one or more selected from the substituted pyridazine compounds and salts thereof described in [1] to [8] above.
  • the compound of the present invention has an excellent control activity against many pathogenic bacteria, and also exhibits a sufficient control effect against pathogenic bacteria that have acquired resistance to existing fungicides. Furthermore, it does not cause phytotoxicity on the target crop, has almost no adverse effect on mammals, fish and beneficial insects, has low persistence, and has a low environmental impact. Therefore, the present invention can provide useful fungicides, particularly agricultural and horticultural fungicides.
  • the compounds encompassed by the present invention may have geometrical isomers of E-forms and Z-forms depending on the type of substituents. And a mixture containing the Z-form in an arbitrary ratio.
  • the compounds included in the present invention may exist as one or two or more rotamers due to limited bond rotation caused by steric hindrance between substituents. Or a mixture of diastereomers including any proportions.
  • the compounds included in the present invention include optically active substances resulting from the presence of one or more asymmetric carbon atoms, but the present invention includes all optically active substances or racemates.
  • the compounds included in the present invention may have tautomers depending on the type of substituent, but the present invention includes all tautomers or a mixture of tautomers included in an arbitrary ratio. Is included.
  • the general formula (1) [wherein R 3 represents a hydroxy group, and R 1 , R 2 and Het have the same meaning as described above. ], The following tautomers are included.
  • those that can be converted into acid addition salts according to a conventional method include, for example, hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, and the like.
  • Salts inorganic acid salts such as nitric acid, sulfuric acid, phosphoric acid, chloric acid, perchloric acid, sulfonic acid salts such as methanesulfonic acid, ethanesulfonic acid, trifluoromethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, Salt of carboxylic acid such as formic acid, acetic acid, propionic acid, trifluoroacetic acid, fumaric acid, tartaric acid, succinic acid, maleic acid, malic acid, succinic acid, benzoic acid, mandelic acid, ascorbic acid, lactic acid, gluconic acid, citric acid or the like
  • a salt of an amino acid such as glutamic acid or aspartic acid can be used.
  • those that can be converted into metal salts according to conventional methods include, for example, alkali metal salts such as lithium, sodium, and potassium, and alkaline earth metals such as calcium, barium, and magnesium. It can be a salt or a salt of aluminum.
  • n- means normal
  • i- means iso
  • s- means secondary and tert- means tertiary
  • Ph means phenyl
  • halogen atom in the compound of the present invention examples include fluorine atom, chlorine atom, bromine atom and iodine atom.
  • the notation “halo” also represents these halogen atoms.
  • C a -C b alkyl represents a linear or branched hydrocarbon group having a carbon number of a to b, such as a methyl group, an ethyl group, an n-propyl group, Specific examples include i-propyl group, n-butyl group, i-butyl group, s-butyl group, tert-butyl group, n-pentyl group, 1,1-dimethylpropyl group, n-hexyl group and the like. Each selected range of carbon atoms is selected.
  • C a -C b alkenyl is a linear or branched chain composed of a to b carbon atoms and has one or more double bonds in the molecule.
  • Represents a saturated hydrocarbon group for example, vinyl group, 1-propenyl group, 2-propenyl group, 1-methylethenyl group, 2-butenyl group, 2-methyl-2-propenyl group, 3-methyl-2-butenyl group, 1
  • Specific examples include 1,2-dimethyl-2-propenyl group and the like, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkynyl represents a linear or branched chain having a carbon number of a to b and an unsaturated group having one or more triple bonds in the molecule.
  • halo (C a -C b ) alkyl is linear or branched having a to b carbon atoms in which a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom
  • a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom
  • fluoromethyl group chloromethyl group, bromomethyl group, iodomethyl group, difluoromethyl group, dichloromethyl group, trifluoromethyl group, chlorodifluoromethyl group, trichloromethyl group, bromodifluoromethyl group, 2-fluoroethyl group, 2- Chloroethyl group, 2-bromoethyl group, 2,2-difluoroethyl group, 2,2,2-trifluoroethyl group, 2-chloro-2,2-difluoroethyl group, 2,2,2-trichloroethyl group, 1 , 1,2,2-tetrafluoroethyl group, 2-chloro-1,1,2-trifluoroethyl group, pentafluoroethyl group, 3,3,3-trifluoropropyl group, 2,2,3,3 , 3-pentafluoropropyl group, 1,1,2,3,3,3-hexafluoropropyl group
  • halo (C a -C b ) alkenyl in the present specification is linear or branched having a carbon number of a to b in which a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom
  • An unsaturated hydrocarbon group which is chain-like and has one or more double bonds in the molecule.
  • these halogen atoms may be the same as or different from each other.
  • halo (C a -C b ) alkynyl in the present specification is linear or branched having a carbon number of a to b, wherein a hydrogen atom bonded to a carbon atom is optionally substituted with a halogen atom
  • An unsaturated hydrocarbon group which is chain-like and has one or more triple bonds in the molecule.
  • these halogen atoms may be the same as or different from each other.
  • Specific examples include 2-chloroethynyl group, 2-bromoethynyl group, 2-iodoethynyl group, 3-chloro-2-propynyl group, 3-bromo-2-propynyl group, 3-iodo-2-propynyl group and the like. Each of which is selected for each specified number of carbon atoms.
  • C a -C b alkoxy in the present specification represents an alkyl-O— group having the above-mentioned meaning consisting of a to b carbon atoms, for example, a methoxy group, an ethoxy group, an n-propyloxy group, Specific examples include i-propyloxy group, n-butyloxy group, i-butyloxy group, s-butyloxy group, tert-butyloxy group and the like, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkenyloxy in the present specification represents an alkenyl-O— group having the above-mentioned meaning consisting of a to b carbon atoms, for example, 2-propenyloxy group, 2-butenyloxy group, Specific examples include 2-methyl-2-propenyloxy group, 3-methyl-2-butenyloxy group and the like, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkynyloxy represents an alkynyl-O— group having the above-mentioned meanings comprising a to b carbon atoms, for example, 2-propynyloxy group, 2-butynyloxy group, Specific examples include 3-butynyloxy group and the like, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkylcarbonyl in the present specification represents an alkyl-C (O) -group having the above-mentioned meaning consisting of a to b carbon atoms, for example, acetyl group, propionyl group, butyryl group. Specific examples thereof include an isobutyryl group and the like, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkoxycarbonyl represents an alkyl-O—C (O) — group having the above-mentioned meanings consisting of a to b carbon atoms, for example, methoxycarbonyl group, ethoxycarbonyl Specific examples include a group, n-propyloxycarbonyl group, i-propyloxycarbonyl group, tert-butyloxycarbonyl group and the like, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkylcarbonyloxy represents an alkyl-C (O) —O— group having the above-mentioned meaning of a to b carbon atoms, for example, acetoxy group, propionyloxy Groups and the like are listed as specific examples, and each group is selected within the range of the designated number of carbon atoms.
  • C a -C b alkoxycarbonyloxy in the present specification represents an alkyl-O—C (O) —O— group having the above-mentioned meaning consisting of a to b carbon atoms, such as methoxycarbonyloxy Groups, ethoxycarbonyloxy groups, n-propyloxycarbonyloxy groups, i-propyloxycarbonyloxy groups, i-butyloxycarbonyloxy groups, tert-butyloxycarbonyloxy groups and the like. Selected in the range of the number of carbon atoms.
  • C a -C b alkylthio in the present specification represents an alkyl-S— group having the above-mentioned meaning consisting of a to b carbon atoms, for example, methylthio group, ethylthio group, n-propylthio group, i Specific examples include -propylthio group, n-butylthio group, i-butylthio group, s-butylthio group, tert-butylthio group and the like, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkenylthio in the present specification represents an alkenyl-S— group having the above-mentioned meaning consisting of a to b carbon atoms, for example, 2-propenylthio group, 2-butenylthio group Specific examples include 2-methyl-2-propenylthio group, 3-methyl-2-butenylthio group and the like, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkynylthio in the present specification represents an alkynyl-S-group having the above-mentioned meaning consisting of a to b carbon atoms, such as 2-propynylthio group, 2-butynylthio group, etc. are given as specific examples and are selected in the range of each designated number of carbon atoms.
  • C a -C b alkylsulfinyl represents an alkyl-S (O) -group having the above-mentioned meaning consisting of a to b carbon atoms, such as a methylsulfinyl group, an ethylsulfinyl group, Specific examples include n-propylsulfinyl group, i-propylsulfinyl group, n-butylsulfinyl group, i-butylsulfinyl group, s-butylsulfinyl group, tert-butylsulfinyl group and the like. The range is selected.
  • C a -C b alkenylsulfinyl represents an alkenyl-S (O) -group having the above-mentioned meaning consisting of a to b carbon atoms, such as a 2-propenylsulfinyl group, Specific examples include 2-butenylsulfinyl group, 2-methyl-2-propenylsulfinyl group, 3-methyl-2-butenylsulfinyl group and the like, each selected within the range of the designated number of carbon atoms. .
  • C a -C b alkynylsulfinyl represents an alkynyl-S (O) -group having the above-mentioned meaning consisting of a to b carbon atoms, for example, 2-propynylsulfinyl group, 2- Specific examples include a butynylsulfinyl group and the like, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkylsulfonyl in the present specification represents an alkyl-SO 2 — group having the above-mentioned meanings consisting of a to b carbon atoms, for example, methylsulfonyl group, ethylsulfonyl group, n- Specific examples include propylsulfonyl group, i-propylsulfonyl group, n-butylsulfonyl group, i-butylsulfonyl group, s-butylsulfonyl group, tert-butylsulfonyl group, etc. Selected.
  • C a -C b alkenylsulfonyl represents an alkenyl-SO 2 — group having the above-mentioned meanings consisting of a to b carbon atoms, such as a 2-propenylsulfonyl group, 2- Specific examples include a butenylsulfonyl group, a 2-methyl-2-propenylsulfonyl group, a 3-methyl-2-butenylsulfonyl group, and the like, and each is selected within the range of the designated number of carbon atoms.
  • C a -C b alkynylsulfonyl represents an alkynyl-SO 2 — group having the above-mentioned meaning consisting of a to b carbon atoms, for example, 2-propynylsulfonyl group, 2-butynyl A sulfonyl group etc. are mentioned as a specific example, It selects in the range of each designated carbon atom number.
  • halo (C a -C b ) alkoxy represents a haloalkyl-O-group having the above-mentioned meaning consisting of a to b carbon atoms, such as a difluoromethoxy group, a trifluoromethoxy group, Chlorodifluoromethoxy group, bromodifluoromethoxy group, 2-fluoroethoxy group, 2-chloroethoxy group, 2,2,2-trifluoroethoxy group, 1,1,2,2, -tetrafluoroethoxy group, 2-chloro Specific examples include -1,1,2-trifluoroethoxy group, 1,1,2,3,3,3-hexafluoropropyloxy group, and the like, each selected within the range of the designated number of carbon atoms. .
  • halo (C a -C b ) alkenyloxy represents a haloalkenyl-O— group having the above-mentioned meaning consisting of a to b carbon atoms, for example 2-fluoro-2-propenyl Oxy group, 2-chloro-2-propenyloxy group, 3,3-difluoro-2-propenyloxy group, 3,3-dichloro-2-propenyloxy group, 2,3,3-trifluoro-2-propenyloxy Specific examples include a group, 4,4-difluoro-3-butenyloxy group, 3,4,4-trifluoro-3-butenyloxy group, and the like, and each is selected within the range of the designated number of carbon atoms.
  • halo (C a -C b ) alkynyloxy represents a haloalkynyl-O— group having the above meaning consisting of a to b carbon atoms, for example 3-chloro-2-propynyl Specific examples include oxy group, 3-bromo-2-propynyloxy group, 3-iodo-2-propynyloxy, and the like, and each is selected within the range of the designated number of carbon atoms.
  • halo (C a -C b ) alkylthio represents a haloalkyl-S— group having the above-mentioned meaning consisting of a to b carbon atoms, such as a difluoromethylthio group, a trifluoromethylthio group, Chlorodifluoromethylthio group, bromodifluoromethylthio group, 2,2,2-trifluoroethylthio group, 1,1,2,2-tetrafluoroethylthio group, 2-chloro-1,1,2-trifluoroethylthio group Group, pentafluoroethylthio group, 1,1,2,3,3,3-hexafluoropropylthio group, heptafluoropropylthio group, 1,2,2,2-tetrafluoro-1- (trifluoromethyl)
  • Specific examples include an ethylthio group, a nonafluorobutyl
  • halo (C a -C b ) alkenylthio represents a haloalkenyl-S-group having the above-mentioned meaning consisting of a to b carbon atoms, for example 2-fluoro-2-propenyl Thio group, 2-chloro-2-propenylthio group, 3,3-difluoro-2-propenylthio group, 3,3-dichloro-2-propenylthio group, 2,3,3-trifluoro-2-propenylthio Specific examples include a group, 4,4-difluoro-3-butenylthio group, 3,4,4-trifluoro-3-butenylthio group, and the like, and each is selected within the range of the designated number of carbon atoms.
  • halo (C a -C b ) alkynylthio in the present specification represents a haloalkynyl-S— group having the above meaning consisting of a to b carbon atoms, for example 3-chloro-2-propynyl Specific examples include thio group, 3-bromo-2-propynylthio group, 3-iodo-2-propynylthio and the like, and each is selected within the range of the designated number of carbon atoms.
  • halo (C a -C b ) alkylsulfinyl in the present specification represents a haloalkyl-S (O) -group having the above-mentioned meaning consisting of a to b carbon atoms, such as a difluoromethylsulfinyl group, Trifluoromethylsulfinyl group, chlorodifluoromethylsulfinyl group, bromodifluoromethylsulfinyl group, 2,2,2-trifluoroethylsulfinyl group, 1,2,2,2-tetrafluoro-1- (trifluoromethyl) ethylsulfinyl
  • Specific examples include a group, a nonafluorobutylsulfinyl group, and the like, and each is selected within the range of the designated number of carbon atoms.
  • halo (C a -C b ) alkenylsulfinyl represents a haloalkenyl-S (O) — group having the above-mentioned meaning consisting of a to b carbon atoms, for example 2-fluoro- 2-propenylsulfinyl group, 2-chloro-2-propenylsulfinyl group, 3,3-difluoro-2-propenylsulfinyl group, 3,3-dichloro-2-propenylsulfinyl group, 4,4-difluoro-3-butenyl Specific examples include a sulfinyl group, a 3,4,4-trifluoro-3-butenylsulfinyl group, and the like, and each is selected within the range of the designated number of carbon atoms.
  • halo (C a -C b ) alkynylsulfinyl represents a haloalkynyl-S (O) -group having the above-mentioned meaning consisting of a to b carbon atoms, for example 3-chloro- Specific examples include 2-propynylsulfinyl group, 3-bromo-2-propynylsulfinyl group, 3-iodo-2-propynylsulfinyl group and the like, and each is selected within the range of the designated number of carbon atoms.
  • halo (C a -C b ) alkylsulfonyl in the present specification represents a haloalkyl-SO 2 — group having the above-mentioned meaning consisting of a to b carbon atoms, such as a difluoromethylsulfonyl group, trifluoro Methylsulfonyl group, chlorodifluoromethylsulfonyl group, bromodifluoromethylsulfonyl group, 2,2,2-trifluoroethylsulfonyl group, 1,1,2,2-tetrafluoroethylsulfonyl group, 2-chloro-1,1, Specific examples include 2-trifluoroethylsulfonyl group and the like, and each is selected within the range of the designated number of carbon atoms.
  • halo (C a -C b ) alkenylsulfonyl in the present specification represents a haloalkenyl-SO 2 — group having the above-mentioned meaning consisting of a to b carbon atoms, such as 2-fluoro-2- Propenylsulfonyl group, 2-chloro-2-propenylsulfonyl group, 3,3-difluoro-2-propenylsulfonyl group, 3,3-dichloro-2-propenylsulfonyl group, 4,4-difluoro-3-butenylsulfonyl group Specific examples include 3,4,4-trifluoro-3-butenylsulfonyl group and the like, and each is selected within the range of the designated number of carbon atoms.
  • halo (C a -C b ) alkynylsulfonyl represents a haloalkynyl-SO 2 — group having the above-mentioned meaning consisting of a to b carbon atoms, such as 3-chloro-2-
  • Specific examples include propynylsulfonyl group, 3-bromo-2-propynylsulfonyl group, 3-iodo-2-propynylsulfonyl, and the like, and each is selected within the specified number of carbon atoms.
  • tri (C a -C b ) alkylsilyl in the present specification represents a silicon atom in which three alkyl groups having the above-mentioned meanings consisting of a to b carbon atoms are bonded. These alkyl groups may be the same as or different from each other. For example, trimethylsilyl group, triethylsilyl group, tri (i-propyl) silyl group, i-propyldimethylsilyl group, t-butyldimethylsilyl group and the like are listed as specific examples.
  • the notation of tri (C a -C b ) alkylsilyl in the present specification represents a silicon atom in which three alkyl groups having the above-mentioned meanings consisting of a to b carbon atoms are bonded. These alkyl groups may be the same as or different from each other. For example, trimethylsilyl group, triethylsilyl group, tri (i-prop
  • the expression “3- to 6-membered saturated heterocycle optionally substituted by R i ” refers to a 3- to 6-membered saturated heterocycle in which a hydrogen atom bonded to a carbon atom is substituted by any R i . And may contain one or more heteroatoms selected from an oxygen atom and a sulfur atom as atoms constituting the ring. Specific examples include oxirane, methyloxirane, 3-methyloxetane, tetrahydrofuran, tetrahydropyran and the like. At this time, when there are two or more substituents R i on each 3- to 6-membered saturated heterocyclic ring, each R i may be the same as or different from each other.
  • phenyl (C a -C b ) alkyl is an alkyl having the above-mentioned meanings comprising a to b carbon atoms in which a hydrogen atom bonded to a carbon atom is optionally substituted with a phenyl group. Represents a group and is selected for each specified number of carbon atoms.
  • the expression “(C a -C b ) alkyl group optionally substituted with R f ” indicates that the number of carbon atoms in which a hydrogen atom bonded to a carbon atom is substituted with any R f is a to It represents an alkyl group as defined above consisting of b, and is selected within the range of the number of carbon atoms specified.
  • each R f may be the same or different.
  • (C a -C b ) alkenyl group optionally substituted with R f refers to the number of carbon atoms in which a hydrogen atom bonded to a carbon atom is substituted with an arbitrary R f It represents an alkenyl group having the above meaning consisting of b, and is selected within the range of each designated number of carbon atoms.
  • each R f may be the same as or different from each other.
  • the expression “(C a -C b ) alkynyl group optionally substituted by R f ” refers to the case where the number of carbon atoms in which a hydrogen atom bonded to a carbon atom is substituted by any R f is a to It represents an alkynyl group as defined above consisting of b, and is selected within the range of each designated number of carbon atoms. At this time, when there are two or more substituents R f on each (C a -C b ) alkynyl group, each R f may be the same or different.
  • (C a -C b ) alkoxy group optionally substituted by R f refers to the number of carbon atoms in which a hydrogen atom bonded to a carbon atom is substituted by any R f It represents an alkoxy group as defined above consisting of b, and is selected within the range of the respective designated number of carbon atoms. At this time, when there are two or more substituents R f on each (C a -C b ) alkoxy group, each R f may be the same or different.
  • the expression “(C a -C b ) alkenyloxy group optionally substituted by R f ” indicates that the number of carbon atoms in which a hydrogen atom bonded to a carbon atom is substituted by any R f is a Represents an alkenyloxy group as defined above consisting of ⁇ b, each selected within the range of the specified number of carbon atoms. At this time, when there are two or more substituents R f on each (C a -C b ) alkenyloxy group, each R f may be the same or different.
  • (C a -C b ) alkynyloxy group optionally substituted by R f refers to the number of carbon atoms in which a hydrogen atom bonded to a carbon atom is substituted by any R f being a.
  • each R f may be the same as or different from each other.
  • Specific examples of the notation include, for example, aziridine, azetidine, pyrrolidine, piperidine,
  • the compound of the present invention is generally used as a sterilizing / fungicidal agent for agricultural and horticultural use in various diseases caused by root-knot fungi, oomycetes, zygomycetes, ascomycetes, basidiomycetes, imperfect fungi, bacteria or viruses. Can be used against.
  • Rice blast Pieraria oryzae
  • sesame leaf blight Cochliobolus miyabeanus
  • blight Rhizoctonia solani
  • rice mildew Claviceps virenk
  • leaf seedling Gibberk
  • Rhizopus spp. Trichoderma viride
  • bacterial disease Disease Acidovorax avenae
  • bacterial leaf blight Xanthomonas oryzae
  • the inner ⁇ Henbyo Erwinia ananas
  • Wheat yellow mosaic virus Barley yellow mosaic virus
  • wheat powdery mildew Erysiphe graminis f. Sp. Hordei, E. graminis leaf, E. graminis leaf disease.
  • (Pyrenophora graminea) net blotch disease
  • Rhizopus spp. Trichoderma viride
  • bacterial disease Disease Acidovorax avenae
  • bacterial leaf blight Xanthomonas oryzae
  • the inner ⁇ Henbyo Erwinia ananas
  • Wheat yellow mosaic virus Barley yellow mosaic virus
  • wheat powdery mildew Erysiphe graminis f. Sp. Hordei, E. gramin
  • scab Xanthomonas campestris
  • gray mold Bt Mongolia disease of Mongolia (Monilinia mali), rot (Valsa mali), powdery mildew (Podosphaera leukotricha), spotted leaf disease (Alternaria maria), black star disease (Venturia inaequalis) Pear black spot disease (Venturia nashiicola), black spot disease (Alternaria kikuchiana), red star disease (Gymnosporium rhidium aiaticum), epidemic disease (Phytophthora certocidal, P. syringae), leaf charcoal disease.
  • Powdery mildew (Phyllactinia mary), Peach ash streak (Monilinia fracticola), black streak (Cladosporium carpophilum), pomopsis spoilage (Phomopsis crisp), pneumopathic disease (Pseudocercospora circumssis, phyllopsis) deformans), peach scab (Pseudomonas syringae pv. morsprunorum), ash scab (Monilinia frusticola), black spot (Xanthomonas campestris pv. Japanese scab (Pseudomonas syringae pv.
  • Glycines Glycines
  • purpura Cercospora kikuchii
  • black disease Groundnut black astringency Mycosphaerella personata
  • brown spot Mycosphaerella arachidis
  • pea powdery mildew Erysiphe pisi
  • Strawberry powdery mildew Sphaerotheca aphanis
  • yellowing Fusarium oxysporum
  • wilt Verticillium dacteria
  • plague Phytophthora cactorum, black spot
  • Potato disease Mycosphaerella fragaliae
  • anthracnose Coldletotrichum acutatum, C.
  • Vitians Big Bain's disease (Lettuce big-vein virus), rot disease (Pseudomonas cichoriai, P. marginalis pv. Marginalis disease, P. marginalis pv. Burdock wilt disease (Fusarium oxysporum), black bruise (Rhizoctonia solani), black stripe disease (Itersonilia perplexans), black spot bacterial disease (Xanthomomonas camphorsis disease pv.
  • the compounds of the present invention are antibacterial and antifungal agents such as medical antibacterial agents, animal antibacterial agents, wood, paper / pulp, adhesives / paints, fibers, leather, etc. It can also be used as an industrial disinfectant such as a cooling water channel in a manufacturing plant.
  • the antimicrobial agent for medical use of the compound of the present invention the pathogenic bacteria targeted as an antimicrobial agent for animals, Trichophyton rubrum, Trichophyton mentagrophytes, etc. Ringworm fungi, Candida albicans, Candida fungi, Aspergillus fumigatus fungi, E. coli, etc. Gram-negative bacteria such as Haemophilus influenzae, Gram-positive bacteria such as Staphylococcus aureus, Streptococcus pyogenes, and the like. It is not limited to only.
  • strains targeted as antibacterial and antifungal agents for wood, paper / pulp, adhesives / paints, fibers, leather, etc. Tyromyces palustris, wood-rotting fungi such as Coriolus versicolor, Aspergillus niger, Aspergillus terreus, Eurotium tonophilum, Penicillium citrinum, Penicillium funiculosum, Rhizopus oryzae, Cladosporium cladosporioides, Aureobasidium pullulans, Gliocladium virens, Chaetomium globosum, Fusarium moniliforme, of materials such as Myrothecium verrucaria Examples include degraded microorganisms.
  • strains that are targeted as industrial fungicides include slime fungi such as Sphaerotilis natans and Zoogloea ramigera, but the present invention is not limited thereto.
  • the compound of the present invention can be used not only as an agricultural and horticultural fungicide but also as an endoparasite control agent for livestock, poultry, pets and the like.
  • the endoparasite which is a target of the present invention compound as an endoparasite control agent Haemonchus, Trichostrongillus, Ostertagia, Nematodirus, Cooperia, Ascarisum, Bnost Genus (Oesophagostoumum), Chabertia (Chabertia), Trichuris (Trichuris), Strongylus (Trichonelus), Dictiocaurus (Dictyocaurus), Capriella i ), Toxocara , Asuka Lydia genus (Ascaridia), Okishiurisu genus (Oxyuris), Anne kilometers stoma genus (Ancylostoma), Unshinaria genus (Uncinaria), Tokisasukarisu genus (Toxascaris), nematodes such as Parasukarisu genus (Parascaris), Filariidae nematodes such as Wuchereria, Brugia,
  • elegans (Diphyllobothrium latum), C. elegans (Diphyllobothrium erinacei), Ecinococcus granulosus, Echinococcus multiloculus, etc. Fasciola hepatica (F. gigantica), Westermann pulmonary fluke (Paragonimus westermanii), hypertrophic fluke (Fasciolopsic brilliant), C.
  • each R a when there are a plurality of substituents R a in the compound (when m represents an integer of 2 to 4), each R a may represent the same group or a different group, and the substituent R b ( R b1 and R b2 ) (when p1 and p2 represent an integer of 2 to 4 and q1 represents an integer of 2 to 4), each R b (R b1 and R b2 ) is the same group or Different groups may be represented.
  • examples of the range of the substituent represented by R 3 include the following groups. That is, R 3 I: hydrogen atom, hydroxy group, mercapto group, halogen atom, cyano group, C 1 -C 6 alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, halo (C 1- C 6 ) alkyl group, C 1 -C 6 alkoxy group, halo (C 1 -C 6 ) alkoxy group, C 2 -C 6 alkenyloxy group, C 2 -C 6 alkynyloxy group, C 1 -C 6 alkylthio group Halo (C 1 -C 6 ) alkylthio group, C 1 -C 6 alkylsulfinyl group, halo (C 1 -C 6 ) alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, halo (C 1 -C 6 alky
  • R 3 II hydrogen atom, hydroxy group, halogen atom, cyano group, C 1 -C 6 alkyl group, halo (C 1 -C 6 ) alkyl group, C 1 -C 6 alkoxy group, halo (C 1 -C 6 ) An alkoxy group, a C 1 -C 6 alkylthio group, a C 1 -C 6 alkylsulfinyl group, a C 1 -C 6 alkylsulfonyl group, —C (O) NH 2 , —C (S) NH 2 .
  • R 3 III hydrogen atom, halogen atom, cyano group, C 1 -C 6 alkyl group, halo (C 1 -C 6 ) alkyl group, C 1 -C 6 alkoxy group, halo (C 1 -C 6 ) alkoxy group A C 1 -C 6 alkylthio group, a C 1 -C 6 alkylsulfinyl group, a C 1 -C 6 alkylsulfonyl group.
  • R 3 IV halogen atom, cyano group, C 1 -C 6 alkyl group, C 1 -C 6 alkoxy group.
  • examples of the range of the substituent represented by Ra include the following groups. That is, R a I: optionally substituted by a hydroxy group, mercapto group, halogen atom, nitro group, cyano group, formyl group, carboxyl group, C 1 -C 6 alkyl group, R f (C 1 -C 6 ) An alkyl group [wherein R f is a hydroxy group, a mercapto group, a cyano group, a nitro group, a C 1 -C 6 alkoxy group, a C 1 -C 6 alkylthio group, a C 1 -C 6 alkylsulfinyl group, a C 1 -C 6- to 6-membered optionally substituted by an alkylsulfonyl group, tri (C 1 -C 6 ) alkylsilyl group, phenyl group, —NH 2 , —NHR g , —N
  • R f is a hydroxy group, a mercapto group, a cyano group, a nitro group, C 1 ⁇ C 6 Alkoxy group, C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, tri (C 1 -C 6 ) alkylsilyl group, phenyl group, —NH 2 , —NHR g , —N (R h ) R
  • R f, R f is hydroxy group , Mercapto group, cyano group, nitro group, C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, tri (C 1 -C 6 ) represents a 3- to 6-membered saturated heterocyclic ring optionally substituted with an alkylsilyl group, a phenyl group, —NH 2 , —NHR g , —N (R h ) R g , or R i , R g , R h And R i each independently represents a C 1 -C 6 alkyl group.
  • R a II a hydroxy group, a mercapto group, a halogen atom, a nitro group, a cyano group, C 1 ⁇ C 6 alkyl group, optionally substituted by R f (C 1 ⁇ C 6 ) alkyl group [wherein, R f Is a hydroxy group, mercapto group, cyano group, nitro group, C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, tri (C 1 ⁇ C 6) alkylsilyl group, a phenyl group, -NH 2, -NHR g, -N (R h) R g, or represents 3-6 membered saturated heterocyclic ring optionally substituted by R i, R g , R h and R i each independently represents a C 1 -C 6 alky
  • R f is a hydroxy group, a mercapto group, a cyano group, a nitro group, C 1 ⁇ C 6 Alkoxy group, C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, tri (C 1 -C 6 ) alkylsilyl group, phenyl group, —NH 2 , —NHR g , —N (R h ) R
  • R a III hydroxy group, halogen atom, nitro group, cyano group, C 1 -C 6 alkyl group, halo (C 1 -C 6 ) alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group , C 1 ⁇ C 6 alkoxy group, optionally substituted by R f (C 1 ⁇ C 6 ) alkoxy group [wherein, R f is a hydroxy group, a mercapto group, a cyano group, a nitro group, C 1 ⁇ C 6 Alkoxy group, C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, tri (C 1 -C 6 ) alkylsilyl group, phenyl group, —NH 2 , —NHR g , —N (R h ) R g ,
  • R a IV hydroxy group, halogen atom, cyano group, C 1 -C 6 alkyl group, halo (C 1 -C 6 ) alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, C 1 ⁇ C 6 alkoxy group, optionally substituted by R f (C 1 ⁇ C 6 ) alkoxy group [wherein the R f C 1 ⁇ C 6 alkoxy group, a phenyl group or -N (R h) R g R g and R h each independently represents a C 1 -C 6 alkyl group.
  • Halo (C 1 -C 6 ) alkoxy group C 2 -C 6 alkenyloxy group, C 2 -C 6 alkynyloxy group, C 1 -C 6 alkylthio group, C 2 -C 6 alkenylthio group, C 2 -C 6 alkynylthio group, C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group.
  • R a V halogen atom, cyano group, C 1 -C 6 alkyl group, halo (C 1 -C 6 ) alkyl group, C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, C 1 -C 6 Alkoxy group, halo (C 1 -C 6 ) alkoxy group, C 2 -C 6 alkenyloxy group, C 2 -C 6 alkynyloxy group, C 1 -C 6 alkylthio group, halo (C 1 -C 6 ) alkylthio group A C 2 -C 6 alkenylthio group, a C 2 -C 6 alkynylthio group.
  • examples of the range of the substituent represented by R b1 include the following groups. That is, R b1 I: a hydroxy group, a mercapto group, a halogen atom, a nitro group, a cyano group, a C 1 -C 6 alkyl group, a (C 1 -C 6 ) alkyl group optionally substituted by R f [where, R f is a hydroxy group, mercapto group, cyano group, nitro group, formyl group, carboxyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, C 1- C 6 alkylsulfonyl group, a tri (C 1 ⁇ C 6) alkylsilyl group, a phenyl group, -NH 2, -NHR g, -N (R h) R g, -C
  • R g and R h each independently represent C 1 ⁇ C 6 alkyl group
  • R i is C 1 ⁇ Represents a C 6 alkyl group, a halo (C 1 -C 6 ) alkyl group or a phenyl group.
  • R f is hydroxy Group, mercapto group, cyano group, nitro group, formyl group, carboxyl group, C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group , Tri (C 1 -C 6 ) alkylsilyl group, phenyl group, —NH 2 , —NHR g , —N (R h ) R g , —C (O) R i , —C (O) OR i , — C (O) NH 2, represents a -C (O) NHR g, -C (O)
  • a halo (C 2 -C 6 ) alkynyloxy group —OC (O) R i wherein R i represents a C 1 -C 6 alkyl group, a halo (C 1 -C 6 ) alkyl group or a phenyl group.
  • R i represents a C 1 -C 6 alkyl group, a halo (C 1 -C 6 ) alkyl group or a phenyl group.
  • R d2 and R e2 are each independently a C 1 -C 4 alkyl group, a halo (C 1 -C 4 ) alkyl group, or a C 2 -C 5 alkenyl group. , C 2 -C 5 alkynyl group, C 1 -C 4 alkylsulfonyl group, —C (O) R i , —C (O) OR i or —CH ⁇ N—OR i , wherein R i represents C 1 to Represents a C 6 alkyl group or a halo (C 1 -C 6 ) alkyl group.
  • R d2 and R e2 are each independently a C 1 -C 4 alkyl group, a halo (C 1 -C 4 ) alkyl group, or —CH ⁇ N-OR i , R i represents a C 1 -C 6 alkyl group or a halo (C 1 -C 6 ) alkyl group.
  • R d2 represents a C 1 -C 6 alkyl group.
  • R b1 II hydroxy groups, halogen atom, nitro group, cyano group, C 1 ⁇ C 6 alkyl group, have been (C 1 ⁇ C 6) alkyl group [wherein optionally substituted by R f, R f is cyano Group, nitro group, C 1 -C 6 alkoxy group, C 1 -C 6 alkylthio group, tri (C 1 -C 6 ) alkylsilyl group, phenyl group, —NH 2 , —NHR g , —N (R h ) R g , —C (O) R i , —C (O) OR i , or R i represents a 3- to 6-membered saturated heterocycle optionally substituted by R i , and R g and R h are each independently C 1 Represents a C 6 alkyl group, and R i represents a C 1 -C 6 alkyl group, a halo (C 1 -C 6 al
  • R g and R h each independently represents a C 1 -C 6 alkyl group
  • R i represents a C 1 -C 6 alkyl group, a halo (C 1 -C 6 ) alkyl group or a phenyl group.
  • R f is cyano group
  • R f C 2 ⁇ C 6 alkynyloxy group, optionally substituted by R f (C 2 ⁇ C 6 ) alkynyloxy group
  • R f is cyano group, nitro group, C 1 ⁇ C 6 alkoxy group , C 1 -C 6 alkylthio group, tri (C 1 -C 6 ) alkylsilyl group, phenyl group, —NH 2 , —NHR g , —N (R h ) R g , —C (O) R i , — C (O) OR i or a 3- to 6-membered saturated heterocyclic ring optionally substituted by R i , R g and R h each independently represent a C 1 -C 6 alkyl group, and R i represents C It represents a 1 to C 6 alkyl group, a halo (C 1 to C 6 ) alkyl group or a phenyl group.
  • R i represents a C 1 -C 6 alkyl group, a halo (C 1 -C 6 ) alkyl group or a phenyl group.
  • OR i represents a C 1 -C 6 alkyl group, a halo (C 1 -C 6 ) alkyl group or a phenyl group.
  • R d2 and R e2 are each independently a C 1 -C 4 alkyl group, a halo (C 1 -C 4 ) alkyl group, or a C 2 -C 5 alkenyl group. , C 2 -C 5 alkynyl group, C 1 -C 4 alkylsulfonyl group, —C (O) R i , —C (O) OR i or —CH ⁇ N—OR i , wherein R i represents C 1 to Represents a C 6 alkyl group or a halo (C 1 -C 6 ) alkyl group.
  • R b1 III hydroxy groups, halogen atoms, cyano groups, C 1 ⁇ C 6 alkyl group, optionally been (C 1 ⁇ C 6) alkyl group [wherein substituted by R f, is R f, cyano groups, C 1 to C 6 alkoxy group, C 1 to C 6 alkylthio group, tri (C 1 to C 6 ) alkylsilyl group, phenyl group, —C (O) R i , —C (O) OR i , or R i R 3 represents an optionally substituted 3- to 6-membered saturated heterocyclic ring, and R i represents a C 1 -C 6 alkyl group, a halo (C 1 -C 6 ) alkyl group, or
  • R f is cyano groups, C 1 to C 6 alkoxy group, C 1 to C 6 alkylthio group, tri (C 1 to C 6 ) alkylsilyl group, phenyl group, —C (O) R i , —C (O) OR i , or R i R 3 represents an optionally substituted 3- to 6-membered saturated heterocyclic ring
  • R i represents a C 1 -C 6 alkyl group, a halo (C 1 -C 6 ) alkyl group, or a phenyl group.
  • C 1 -C 6 alkylthio group C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group, —NH 2 , —NHR d2
  • R d2 represents a C 1 -C 4 alkyl group, C 1 -C 4 alkylsulfonyl group, —C (O) R i , —C (O) OR i or —CH ⁇ N—OR i , where R i is a C 1 -C 6 alkyl group or halo (C 1 To C 6 ) represents an alkyl group.
  • R d2 and R e2 are each independently a C 1 -C 4 alkyl group, a C 1 -C 4 alkylsulfonyl group, -C (O) R i ,- C (O) OR i or —CH ⁇ N—OR i , where R i represents a C 1 -C 6 alkyl group or a halo (C 1 -C 6 ) alkyl group.
  • - N CH-N (R h) R g [ wherein, each independently is R g and R h represents a C 1 ⁇ C 6 alkyl group.
  • R b1 IV halogen atom, cyano group, C 1 -C 6 alkyl group, halo (C 1 -C 6 ) alkyl group, C 1 -C 6 alkoxy group, optionally substituted by R f (C 1 -C 6 ) an alkoxy group [wherein R f is optionally substituted by a cyano group, a C 1 -C 6 alkoxy group, a C 1 -C 6 alkylthio group, a tri (C 1 -C 6 ) alkylsilyl group, or R i Represents a 3- to 6-membered saturated heterocyclic ring, and R i represents a C 1 -C 6 alkyl group.
  • Halo (C 1 -C 6 ) alkoxy group C 2 -C 6 alkenyloxy group, C 2 -C 6 alkynyloxy group, C 1 -C 6 alkylthio group, C 1 -C 6 alkylsulfinyl group, C 1 -C 6 alkylsulfonyl group.
  • R b1 V halogen atom, cyano group, C 1 ⁇ C 6 alkyl group, optionally substituted (C 1 ⁇ C 6) alkoxy group
  • R f, R f is cyano group
  • C 1 ⁇ C 6 represents an alkoxy group, a C 1 -C 6 alkylthio group, a tri (C 1 -C 6 ) alkylsilyl group, or oxiran-2-yl.
  • Halo (C 1 -C 6 ) alkyl group C 2 -C 6 alkenyl group, C 2 -C 6 alkynyl group, C 1 -C 6 alkoxy group, halo (C 1 -C 6 ) alkoxy group, C 2 -C 6 alkenyloxy group, C 2 -C 6 alkynyloxy group, C 1 -C 6 alkylthio group, halo (C 1 -C 6 ) alkylthio group, C 2 -C 6 alkenylthio group, C 2 -C 6 alkynyl Thio group.
  • examples of the range of the substituent represented by R b2 include the following groups.
  • R b2 I halogen atom, nitro group, cyano group, C 1 -C 6 alkyl group, halo (C 1 -C 6 ) alkyl group, C 1 -C 6 alkoxy group, halo (C 1 -C 6 ) alkoxy group
  • R b2 II halogen atom, nitro group, cyano group, C 1 -C 6 alkyl group, hal
  • R 31 represents a chlorine atom or a bromine atom
  • R 1 , R 2 and Het have the same meaning as described above.
  • the compound of the present invention represented by the general formula (1-1) is prepared by reacting the compound represented by the general formula (2) or a salt thereof with a halogenating agent in a solvent or without a solvent, and optionally in the presence of a base. Can be obtained.
  • the solvent used may be inert to the reaction, and examples thereof include hydrocarbons such as toluene, nitriles such as acetonitrile, halogenated hydrocarbons such as 1,2-dichloroethane, and the like.
  • Preferable examples include toluene and 1,2-dichloroethane.
  • the halogenating agent include phosphorus oxychloride and phosphorus oxybromide.
  • phosphorus oxychloride can also be used as a solvent.
  • a halogenating agent it can be used in 0.1-100 equivalent with respect to compound (2), and the range of 1-50 equivalent is preferable.
  • examples of the base used include N, N-diethylaniline, N, N-dimethylaniline, triethylamine, diisopropylethylamine, pyridine, 5-ethyl-2-picoline, tributylamine, N, N-dimethylaniline.
  • the reaction temperature can be from room temperature to the reflux temperature of the reaction mixture, and preferably from 50 ° C. to the reflux temperature of the reaction mixture.
  • the reaction time can be 5 minutes to 100 hours, and preferably 1 hour to 48 hours. After completion of the reaction, the compound represented by the general formula (1-1) can be obtained from the reaction solution by ordinary post-treatment.
  • the compound represented by the general formula (1-1) can be obtained by adding the reaction mixture to water and collecting the precipitated solid by filtration.
  • water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform are added to the reaction mixture for extraction, and then the organic layer is dried and concentrated to obtain compound (1-1).
  • an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform
  • the organic layer is dried and concentrated to obtain compound (1-1).
  • it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • the compound represented by the general formula (1-2) in which R 3 is a C 1 -C 6 alkoxy group or a C 1 -C 6 alkylthio group includes, for example, the general formula (1-1) It can manufacture by making the compound represented and the compound represented by General formula (21) react.
  • the compound of the present invention represented by the general formula (1-2) is a compound represented by the general formula (1-1) and the compound represented by the general formula (21) in a solvent or without a solvent. Can be obtained by reacting in the presence of a base. When a solvent is used, the solvent used may be inert to the reaction.
  • lower alcohols such as methanol and ethanol
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane and 1,2-dimethoxyethane
  • Aromatic hydrocarbons such as benzene, xylene, toluene, aliphatic hydrocarbons such as pentane, hexane, cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane, acetonitrile, propionitrile, etc.
  • Nitriles N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone and other amides, dimethyl sulfoxide or a mixed solvent thereof.
  • Preferable examples include alcohols corresponding to R 32 , tetrahydrofuran, N, N-dimethylformamide, N-methylpyrrolidone, and mixtures thereof.
  • the reaction can be performed in the presence of a base.
  • Examples of the base that can be used include pyridine, 2,6-lutidine, 4-dimethylaminopyridine, triethylamine, diisopropylethylamine, tributylamine, N, N-dimethylaniline, 1,4-diazabicyclo [2.2.2].
  • Organic bases such as octane (DABCO), 1,8-diazabicyclo [5.4.0] -7-undecene (DBU) or 1,5-diazabicyclo [4.3.0] -5-nonene (DBN);
  • Inorganic bases such as sodium hydride, sodium hydrogen carbonate, potassium carbonate, cesium carbonate and the like can be mentioned.
  • the equivalent of the base it can be used in the range of 0.1 to 100 equivalents relative to the compound represented by the general formula (1-1), and the range of 1 to 40 equivalents is preferable.
  • the reaction temperature can be arbitrarily set from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of 0 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours.
  • compound (21) can be used in the range of 0.5 to 50 equivalents relative to compound (1-1), and preferably in the range of 1 to 20 equivalents.
  • the compound represented by the general formula (1-2) can be obtained from the reaction solution by ordinary post-treatment.
  • water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform are added to the reaction mixture for extraction, and then the organic layer is dried and concentrated to give compound (1-2).
  • an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform
  • the compound represented by the general formula (1-3) in which R 3 is a fluorine atom is obtained by reacting, for example, a compound represented by the general formula (1-1) with a fluorinating agent.
  • a fluorinating agent for example, a compound represented by the general formula (1-1) with a fluorinating agent.
  • R 31 represents a chlorine atom or a bromine atom
  • R 1 , R 2 and Het have the same meaning as described above.
  • the compound of the present invention represented by the general formula (1-3) is obtained by reacting the compound represented by the general formula (1-1) with a fluorinating agent in a solvent or without a solvent, and optionally in the presence of a base. Can be obtained.
  • the solvent used may be inert to the reaction.
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, and aromatics such as benzene, xylene, and toluene.
  • Hydrocarbons aliphatic hydrocarbons such as pentane, hexane and cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane, nitriles such as acetonitrile and propionitrile, N, N-dimethyl
  • amides such as formamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone, dimethyl sulfoxide or a mixed solvent thereof.
  • Preferred examples include tetrahydrofuran, N, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and mixtures thereof.
  • Examples of the fluorinating agent include potassium fluoride and tetrabutylphosphonium hydrogen difluoride.
  • the equivalent amount of the fluorinating agent can be used in the range of 0.5 to 50 equivalents relative to the compound (1-1), and preferably in the range of 1 to 20 equivalents.
  • the reaction can be performed in the presence of a base.
  • Examples of the base that can be used include pyridine, 2,6-lutidine, 4-dimethylaminopyridine, triethylamine, diisopropylethylamine, tributylamine, N, N-dimethylaniline, 1,4-diazabicyclo [2.2.2].
  • Organic bases such as octane (DABCO), 1,8-diazabicyclo [5.4.0] -7-undecene (DBU) or 1,5-diazabicyclo [4.3.0] -5-nonene (DBN);
  • Inorganic bases such as sodium hydride, sodium hydrogen carbonate, potassium carbonate, cesium carbonate and the like can be mentioned.
  • the equivalent of the base it can be used in the range of 0.1 to 100 equivalents relative to the compound represented by the general formula (1-1), and the range of 1 to 40 equivalents is preferable.
  • the reaction temperature can be arbitrarily set from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of 0 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours.
  • the compound represented by the general formula (1-3) can be obtained from the reaction solution by ordinary post-treatment. For example, water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform are added to the reaction mixture for extraction, and then the organic layer is dried and concentrated to obtain the compound represented by the general formula (1-3). . When it becomes necessary to purify the compound, it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • the compound represented by the general formula (1-4) in which R 3 is a hydrogen atom is obtained by, for example, reacting a compound represented by the general formula (1-1) with a palladium catalyst.
  • a palladium catalyst in which R 31 is a hydrogen atom.
  • R 31 represents a chlorine atom or a bromine atom, and R 1 , R 2 and Het have the same meaning as described above.
  • the compound of the present invention represented by the general formula (1-4) can be obtained by reacting the compound represented by the general formula (1-1) with a palladium catalyst in a solvent or without a solvent in the presence of a base. it can.
  • the solvent used may be inert to the reaction, such as water, lower alcohols such as methanol and ethanol, diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like.
  • Ethers aromatic hydrocarbons such as benzene, xylene and toluene, aliphatic hydrocarbons such as pentane, hexane and cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane, acetonitrile and propio Nitriles such as nitrile, amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone, dimethyl sulfoxide or a mixed solvent thereof .
  • aromatic hydrocarbons such as benzene, xylene and toluene
  • aliphatic hydrocarbons such as pentane, hexane and cyclohexane
  • halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane
  • Preferable examples include water, methanol, butanol, tetrahydrofuran, N, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and mixtures thereof.
  • the palladium catalyst include tetrakis (triphenylphosphine) palladium (0), [1,3-bis (diphenylphosphino) propane] palladium diacetate (II), and the like.
  • the equivalent amount of the palladium catalyst can be used in the range of 0.005 to 20 equivalents relative to the compound (1-1), and preferably in the range of 0.01 to 5 equivalents.
  • Examples of the base include pyridine, 2,6-lutidine, 4-dimethylaminopyridine, triethylamine, diisopropylethylamine, tributylamine, N, N-dimethylaniline, 1,4-diazabicyclo [2.2.2] octane (DABCO).
  • Organic bases such as 1,8-diazabicyclo [5.4.0] -7-undecene (DBU) or 1,5-diazabicyclo [4.3.0] -5-nonene (DBN), sodium hydride
  • Examples include inorganic bases such as sodium hydrogen carbonate, potassium carbonate, cesium carbonate.
  • the equivalent of the base can be used in the range of 0.1 to 100 equivalents relative to the compound (1-1), and preferably in the range of 1 to 40 equivalents.
  • the reaction temperature can be arbitrarily set from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of 0 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours. After completion of the reaction, the compound represented by the general formula (1-4) can be obtained from the reaction solution by ordinary post-treatment.
  • the compound represented by the general formula (1-5) in which R 3 is a C 1 -C 6 alkyl group includes, for example, a compound represented by the general formula (1-1) and an alkylation It can manufacture by making an agent react.
  • R 31 represents a chlorine atom or a bromine atom
  • R 33 represents a C 1 -C 6 alkyl group
  • R 1 , R 2, and Het have the same meaning as described above.
  • the compound of the present invention represented by the general formula (1-5) comprises the compound represented by the general formula (1-1) and an alkylating agent in the presence of a catalyst in a solvent or in the absence of a solvent. It can be obtained by the following reaction.
  • the solvent used may be inert to the reaction, such as water, lower alcohols such as methanol and ethanol, diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like.
  • Ethers aromatic hydrocarbons such as benzene, xylene and toluene, aliphatic hydrocarbons such as pentane, hexane and cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane, acetonitrile and propio Nitriles such as nitrile, amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone, dimethyl sulfoxide or a mixed solvent thereof .
  • aromatic hydrocarbons such as benzene, xylene and toluene
  • aliphatic hydrocarbons such as pentane, hexane and cyclohexane
  • halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane
  • Preferred examples include tetrahydrofuran, N, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and mixtures thereof.
  • examples of the alkylating agent include 2,4,6-trimethylboroxine and methylmagnesium chloride.
  • the equivalent of the alkylating agent can be used in the range of 0.5 to 50 equivalents relative to compound (1-1), and preferably in the range of 1 to 20 equivalents.
  • the catalyst examples include tetrakis (triphenylphosphine) palladium (0), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane adduct, tetrakis (triphenylphosphine) nickel (0), etc. Is mentioned.
  • the equivalent of the catalyst it can be used in the range of 0.005 to 20 equivalents, preferably 0.01 to 5 equivalents, relative to compound (1-1).
  • the reaction can be performed in the presence of a base.
  • Examples of the base that can be used include pyridine, 2,6-lutidine, 4-dimethylaminopyridine, triethylamine, diisopropylethylamine, tributylamine, N, N-dimethylaniline, 1,4-diazabicyclo [2.2.2].
  • Organic bases such as octane (DABCO), 1,8-diazabicyclo [5.4.0] -7-undecene (DBU) or 1,5-diazabicyclo [4.3.0] -5-nonene (DBN);
  • Inorganic bases such as sodium hydride, sodium hydrogen carbonate, potassium carbonate, cesium carbonate and the like can be mentioned.
  • the equivalent of the base can be used in the range of 0.1 to 100 equivalents relative to the compound (1-1), and preferably in the range of 1 to 40 equivalents.
  • the reaction temperature can be arbitrarily set from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of 0 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours. After completion of the reaction, the compound represented by the general formula (1-5) can be obtained from the reaction solution by ordinary post-treatment.
  • the compound represented by the general formula (1-6) in which R 3 is a cyano group is obtained by, for example, reacting a compound represented by the general formula (1-1) with a cyanating agent.
  • a compound represented by the general formula (1-1) with a cyanating agent.
  • R 31 represents a chlorine atom or a bromine atom
  • R 1 , R 2 and Het have the same meaning as described above.
  • the compound of the present invention represented by the general formula (1-6) is obtained by mixing the compound represented by the general formula (1-1) and the cyanating agent in a solvent or without a solvent, optionally in the presence of a base.
  • the solvent used may be inert to the reaction, such as water, lower alcohols such as methanol and ethanol, diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like.
  • Ethers aromatic hydrocarbons such as benzene, xylene and toluene, aliphatic hydrocarbons such as pentane, hexane and cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane, acetonitrile and propio Nitriles such as nitrile, amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone, dimethyl sulfoxide or a mixed solvent thereof .
  • aromatic hydrocarbons such as benzene, xylene and toluene
  • aliphatic hydrocarbons such as pentane, hexane and cyclohexane
  • halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane
  • Preferred examples include tetrahydrofuran, N, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and mixtures thereof.
  • examples of the cyanating agent include potassium cyanide, sodium cyanide, copper cyanide, zinc cyanide and the like.
  • the equivalent of the cyanating agent can be used in the range of 0.5 to 50 equivalents relative to compound (1-1), and preferably in the range of 1 to 20 equivalents.
  • the reaction can be performed in the presence of a base.
  • Examples of the base that can be used include pyridine, 2,6-lutidine, 4-dimethylaminopyridine, triethylamine, diisopropylethylamine, tributylamine, N, N-dimethylaniline, 1,4-diazabicyclo [2.2.2].
  • Organic bases such as octane (DABCO), 1,8-diazabicyclo [5.4.0] -7-undecene (DBU) or 1,5-diazabicyclo [4.3.0] -5-nonene (DBN);
  • Inorganic bases such as sodium hydride, sodium hydrogen carbonate, potassium carbonate, cesium carbonate and the like can be mentioned.
  • the equivalent of the base can be used in the range of 0.1 to 100 equivalents relative to the compound (1-1), and preferably in the range of 1 to 40 equivalents.
  • the reaction can be carried out in the presence of a palladium catalyst.
  • the palladium catalyst examples include tetrakis (triphenylphosphine) palladium (0), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride, dichloromethane adduct, and the like.
  • the equivalent amount of the palladium catalyst can be used in the range of 0.005 to 20 equivalents relative to the compound (1-1), and preferably in the range of 0.01 to 5 equivalents.
  • the reaction temperature can be arbitrarily set from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of 0 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours.
  • the compound represented by the general formula (1-6) can be obtained from the reaction solution by ordinary post-treatment. For example, water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform are added to the reaction mixture for extraction, and then the organic layer is dried and concentrated to obtain the compound represented by the general formula (1-6). . When it becomes necessary to purify the compound, it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • the compound represented by the general formula (1-8) in which R 3 is a C 1 -C 6 alkylsulfinyl group or a C 1 -C 6 alkylsulfonyl group is prepared by, for example, the method of Production Method 2. It can be produced by reacting a compound represented by the general formula (1-7) that can be produced with an oxidizing agent.
  • R 34 represents a C 1 -C 6 alkylthio group
  • R 35 represents a C 1 -C 6 alkylsulfinyl group or a C 1 -C 4 alkylsulfonyl group
  • R 1 , R 2 and Het are as defined above.
  • the compound of the present invention represented by the general formula (1-8) can be produced by the method of Production Method 2 with the compound represented by the general formula (1-7) and the oxidizing agent in a solvent or without solvent.
  • the reaction can be carried out in the presence of a catalyst.
  • the solvent used may be inert to the reaction.
  • lower carboxylic acids such as acetic acid
  • lower alcohols such as methanol and ethanol, diethyl ether, tetrahydrofuran, 1,4-dioxane, 1
  • Ethers such as 2-dimethoxyethane
  • aromatic hydrocarbons such as benzene, xylene and toluene
  • aliphatic hydrocarbons such as pentane, hexane and cyclohexane
  • halogenated carbonization such as dichloromethane, chloroform and 1,2-dichloroethane
  • Nitriles such as hydrogen, acetonitrile, propionitrile, amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone, dimethyl sulfoxide or these And the like.
  • Preferable examples include water, acetic acid, tetrahydrofuran, dichloromethane, chloroform, N-methylpyrrolidone, and mixtures thereof.
  • the oxidizing agent include aqueous hydrogen peroxide, sodium hypochlorite, 3-chloroperbenzoic acid and the like.
  • the equivalent of the oxidizing agent can be used in the range of 0.5 to 50 equivalents relative to compound (1-7), and preferably in the range of 1 to 20 equivalents.
  • the reaction can be carried out in the presence of a catalyst.
  • the catalyst that can be used include sodium tungstate dihydrate.
  • the catalyst can be used in an amount of 0.005 to 20 equivalents, preferably 0.01 to 5 equivalents, relative to compound (1-7).
  • the reaction temperature can be arbitrarily set from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of 0 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours.
  • the compound represented by the general formula (1-8) can be obtained from the reaction solution by ordinary post-treatment. For example, water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform are added to the reaction mixture for extraction, and then the organic layer is dried and concentrated to obtain the compound represented by the general formula (1-8). . When it becomes necessary to purify the compound, it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • a compound represented by the general formula (1-9) wherein Het is a pyridine ring and R a is a C 1 -C 6 alkoxy group or a C 1 -C 6 alkylthio group includes, for example, the following reaction formula It can be manufactured according to the route indicated by (Wherein R a1 represents a chlorine atom, a fluorine atom or a bromine atom, R a2 represents a C 1 to C 6 alkoxy group or a C 1 to C 6 alkylthio group, and A 1 represents a hydrogen atom, a sodium atom or a potassium atom.
  • R 31 represents a chlorine atom or a bromine atom
  • R 1 , R 2 , R a and n represent the same meaning as described above
  • m represents an integer of 0 to 3 only in this case.
  • the compound represented by the general formula (2-1) is a compound represented by the general formula (2) and the compound represented by the general formula (22) in a solvent or without solvent, and in some cases in the presence of a base. It can be obtained by reacting. When a solvent is used, the solvent used may be inert to the reaction.
  • lower alcohols such as methanol and ethanol
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane and 1,2-dimethoxyethane
  • Aromatic hydrocarbons such as benzene, xylene, toluene, aliphatic hydrocarbons such as pentane, hexane, cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane, acetonitrile, propionitrile, etc.
  • Nitriles N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone and other amides, dimethyl sulfoxide or a mixed solvent thereof.
  • Preferred examples include alcohols corresponding to R a2 , tetrahydrofuran, N, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and mixtures thereof.
  • the reaction can be performed in the presence of a base.
  • Examples of the base that can be used include pyridine, 2,6-lutidine, 4-dimethylaminopyridine, triethylamine, diisopropylethylamine, tributylamine, N, N-dimethylaniline, 1,4-diazabicyclo [2.2.2].
  • Organic bases such as octane (DABCO), 1,8-diazabicyclo [5.4.0] -7-undecene (DBU) or 1,5-diazabicyclo [4.3.0] -5-nonene (DBN);
  • Inorganic bases such as sodium hydride, sodium hydrogen carbonate, potassium carbonate, cesium carbonate and the like can be mentioned.
  • the equivalent of the base it can be used in the range of 0.1 to 100 equivalents relative to the compound (2), and the range of 1 to 40 equivalents is preferable.
  • compound (22) can be used in the range of 0.5 to 50 equivalents relative to compound (2), and preferably in the range of 1 to 20 equivalents.
  • the reaction temperature can be arbitrarily set from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of 0 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours.
  • the compound represented by the general formula (2-1) can be obtained from the reaction solution by ordinary post-treatment.
  • compound (2-1) can be obtained by adding water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform to the reaction mixture and extracting the organic layer after drying.
  • an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform
  • it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • the compound of the present invention represented by the general formula (1-9) can be produced by reacting the compound represented by the general formula (2-1) or a salt thereof according to the method described in Production Method 1. Can do.
  • a compound represented by the general formula (1-10) in which Het is a pyridine ring and R a is a cyano group can be produced, for example, according to the route represented by the following reaction formula.
  • R a1 represents a chlorine atom, a fluorine atom or a bromine atom
  • R 31 represents a chlorine atom or a bromine atom
  • R 1 , R 2 , R a and n represent the same meaning as described above.
  • m represents an integer of 0 to 3.
  • the compound represented by the general formula (2-2) is a compound represented by the general formula (2) and a cyanating agent in a solvent or without a solvent, optionally in the presence of a palladium catalyst, and optionally a base. It can be obtained by reacting in the presence. When a solvent is used, the solvent used may be inert to the reaction.
  • lower alcohols such as methanol and ethanol
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane and 1,2-dimethoxyethane
  • Aromatic hydrocarbons such as benzene, xylene, toluene, aliphatic hydrocarbons such as pentane, hexane, cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane, acetonitrile, propionitrile, etc.
  • Nitriles N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone and other amides, dimethyl sulfoxide or a mixed solvent thereof.
  • Preferred examples include tetrahydrofuran, N, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and mixtures thereof.
  • the cyanating agent include potassium cyanide, sodium cyanide, copper cyanide, zinc cyanide and the like. The equivalent of the cyanating agent can be used in the range of 0.5 to 50 equivalents relative to the compound (2), and preferably in the range of 1 to 20 equivalents.
  • the reaction can be carried out in the presence of a palladium catalyst.
  • a palladium catalyst examples include tetrakis (triphenylphosphine) palladium (0), [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride, dichloromethane adduct, and the like.
  • a palladium catalyst it can be used in 0.005 to 20 equivalent with respect to compound (2), and 0.01 to 5 equivalent is preferable.
  • the reaction can be performed in the presence of a base.
  • Examples of the base that can be used include pyridine, 2,6-lutidine, 4-dimethylaminopyridine, triethylamine, diisopropylethylamine, tributylamine, N, N-dimethylaniline, 1,4-diazabicyclo [2.2.2].
  • Organic bases such as octane (DABCO), 1,8-diazabicyclo [5.4.0] -7-undecene (DBU) or 1,5-diazabicyclo [4.3.0] -5-nonene (DBN);
  • Inorganic bases such as sodium hydride, sodium hydrogen carbonate, potassium carbonate, cesium carbonate and the like can be mentioned.
  • the equivalent of the base it can be used in the range of 0.1 to 100 equivalents relative to the compound (2), and the range of 1 to 40 equivalents is preferable.
  • the reaction temperature can be arbitrarily set from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of 0 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours. After completion of the reaction, the compound represented by the general formula (2-2) can be obtained from the reaction solution by ordinary post-treatment.
  • compound (2-2) can be obtained by adding water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform to the reaction mixture, followed by extraction, drying and concentration of the organic layer.
  • an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform
  • it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • the compound of the present invention represented by general formula (1-10) can be produced by reacting the compound represented by general formula (2-2) or a salt thereof according to the method described in Production Method 1. Can do.
  • a compound represented by the general formula (1-12) wherein Het is a pyridine ring and R a is a C 1 -C 4 alkylsulfinyl group or a C 1 -C 4 alkylsulfonyl group is, for example, produced It can be produced by reacting a compound represented by the general formula (1-11), which can be produced by the method of Method 8, with an oxidizing agent.
  • R a1 represents a C 1 -C 6 alkylthio group
  • R a2 represents a C 1 -C 6 alkylsulfinyl group or a C 1 -C 4 alkylsulfonyl group
  • R 1 , R 2 , R 3 , R a and n represent the same meaning as described above, and only m represents an integer of 0 to 3
  • the compound of the present invention represented by the general formula (1-12) can be produced by the method of Production Method 8 with the compound represented by the general formula (1-11) and the oxidizing agent in a solvent or without solvent. In some cases, the reaction can be carried out in the presence of a catalyst. When a solvent is used, the solvent used may be inert to the reaction.
  • lower carboxylic acids such as acetic acid
  • lower alcohols such as methanol and ethanol, diethyl ether, tetrahydrofuran, 1,4-dioxane, 1
  • Ethers such as 2-dimethoxyethane
  • aromatic hydrocarbons such as benzene, xylene and toluene
  • aliphatic hydrocarbons such as pentane, hexane and cyclohexane
  • halogenated carbonization such as dichloromethane, chloroform and 1,2-dichloroethane
  • Nitriles such as hydrogen, acetonitrile, propionitrile, amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone, dimethyl sulfoxide or these And the like.
  • Preferable examples include water, acetic acid, tetrahydrofuran, dichloromethane, chloroform, N-methylpyrrolidone, and mixtures thereof.
  • the oxidizing agent include aqueous hydrogen peroxide, sodium hypochlorite, 3-chloroperbenzoic acid and the like.
  • the equivalent of the oxidizing agent can be used in the range of 0.5 to 50 equivalents relative to compound (1-11), and preferably in the range of 1 to 20 equivalents.
  • the reaction can be carried out in the presence of a catalyst.
  • the catalyst that can be used include sodium tungstate dihydrate.
  • the catalyst can be used in the range of 0.005 to 20 equivalents, preferably 0.01 to 5 equivalents, relative to compound (1-11).
  • the reaction temperature can be arbitrarily set from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of 0 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours.
  • the compound represented by the general formula (1-12) can be obtained from the reaction solution by ordinary post-treatment. For example, water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform are added to the reaction mixture for extraction, and then the organic layer is dried and concentrated to obtain the compound represented by the general formula (1-12). . When it becomes necessary to purify the compound, it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • the compound represented by the general formula (1-14) in which R 1 is a benzene ring and R b is a C 1 -C 6 alkylsulfinyl group or a C 1 -C 6 alkylsulfonyl group is, for example, It can be produced by reacting a compound represented by the general formula (1-13), which can be produced by the above production method, with an oxidizing agent.
  • the compound of the present invention represented by the general formula (1-14) is a compound represented by the general formula (1-13) that can be produced by the above production method and an oxidizing agent in a solvent or without solvent. In some cases, it can be obtained by reacting in the presence of a catalyst.
  • the solvent used may be inert to the reaction.
  • the solvent used may be inert to the reaction.
  • water lower carboxylic acids such as acetic acid, lower alcohols such as methanol and ethanol, diethyl ether, tetrahydrofuran, 1,4-dioxane, 1
  • Ethers such as 2-dimethoxyethane
  • aromatic hydrocarbons such as benzene, xylene and toluene
  • aliphatic hydrocarbons such as pentane, hexane and cyclohexane
  • halogenated carbonization such as dichloromethane, chloroform and 1,2-dichloroethane
  • Nitriles such as hydrogen, acetonitrile, propionitrile, amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone, dimethyl sulfoxide
  • Preferable examples include water, acetic acid, tetrahydrofuran, dichloromethane, chloroform, N-methylpyrrolidone, and mixtures thereof.
  • the oxidizing agent include aqueous hydrogen peroxide, sodium hypochlorite, 3-chloroperbenzoic acid and the like.
  • the equivalent of the oxidizing agent can be used in the range of 0.5 to 50 equivalents relative to compound (1-13), and preferably in the range of 1 to 20 equivalents.
  • the reaction can be carried out in the presence of a catalyst.
  • the catalyst that can be used include sodium tungstate dihydrate.
  • the catalyst can be used in an amount of 0.005 to 20 equivalents, preferably 0.01 to 5 equivalents, relative to compound (1-13).
  • the reaction temperature can be arbitrarily set from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of 0 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours.
  • the compound represented by the general formula (1-14) can be obtained from the reaction solution by ordinary post-treatment. For example, water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform are added to the reaction mixture for extraction, and then the organic layer is dried and concentrated to obtain the compound represented by the general formula (1-14). . When it becomes necessary to purify the compound, it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • the compound represented by the general formula (1-16) in which R 1 is a benzene ring and R b is a hydroxy group is, for example, a compound represented by the general formula (1- It can be produced by reacting the compound represented by 15) with boron tribromide.
  • the compound of the present invention represented by the general formula (1-16) is a compound represented by the general formula (1-15) that can be produced by the above production method and boron tribromide in a solvent or without solvent. And can be obtained by reacting.
  • the solvent used may be inert to the reaction, for example, aromatic hydrocarbons such as benzene, xylene and toluene, aliphatic hydrocarbons such as pentane, hexane and cyclohexane, dichloromethane, chloroform, Halogenated hydrocarbons such as 1,2-dichloroethane or a mixed solvent thereof may be mentioned.
  • aromatic hydrocarbons such as benzene, xylene and toluene
  • aliphatic hydrocarbons such as pentane, hexane and cyclohexane
  • dichloromethane chloroform
  • Halogenated hydrocarbons such as 1,2-dichloroethane or a mixed solvent thereof
  • Preferable examples include toluene, dichloromethane, chloroform, 1,2-dichloroethane, and mixtures thereof.
  • boron tribromide it can be used in the range of 0.5 to 50 equivalents relative to compound (1
  • the reaction temperature can be set at an arbitrary temperature from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of ⁇ 20 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours. After completion of the reaction, the compound represented by the general formula (1-16) can be obtained from the reaction solution by ordinary post-treatment.
  • the compound represented by the general formula (1-17) in which R 3 is —C (O) NH 2 is, for example, a compound represented by the general formula (1- It can be produced by reacting the compound represented by 6) with the compound represented by the general formula (23).
  • a 1 represents a lithium atom, a sodium atom or a potassium atom, and R 1 , R 2 and Het have the same meaning as described above.
  • the compound of the present invention represented by the general formula (1-17) is a compound represented by the general formula (1-6) and a compound represented by the general formula (23) that can be produced by the production method 6.
  • a solvent such as water, lower alcohols such as methanol and ethanol, diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like.
  • Ethers aromatic hydrocarbons such as benzene, xylene and toluene, aliphatic hydrocarbons such as pentane, hexane and cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane, N, N—
  • amides such as dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone, dimethyl sulfoxide or a mixed solvent thereof.
  • Preferable examples include water, methanol, ethanol, tetrahydrofuran, N, N-dimethylformamide, N-methylpyrrolidone, dimethyl sulfoxide, and mixtures thereof.
  • compound (23) can be used in the range of 0.5 to 50 equivalents relative to compound (1-6), and preferably in the range of 1 to 20 equivalents.
  • the reaction can be performed in the presence of an oxidizing agent.
  • the oxidizing agent examples include hydrogen peroxide water.
  • it can be used in the range of 0.005 to 20 equivalents relative to compound (1-6), and preferably in the range of 0.01 to 10 equivalents.
  • the reaction temperature can be arbitrarily set from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of 0 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours.
  • the compound represented by the general formula (1-17) can be obtained from the reaction solution by ordinary post-treatment. For example, water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform are added to the reaction mixture for extraction, and then the organic layer is dried and concentrated to obtain the compound represented by the general formula (1-17). . When it becomes necessary to purify the compound, it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • the compound represented by the general formula (1-18) in which R 3 is —C (S) NH 2 is, for example, a compound represented by the general formula (1- It can be produced by reacting the compound represented by 6) with sodium hydrosulfide.
  • R 1 , R 2 and Het have the same meaning as described above.
  • the compound of the present invention represented by the general formula (1-18) is prepared by reacting the compound represented by the general formula (1-6) and sodium hydrosulfide, which can be produced by the production method 6, in a solvent or without solvent. In some cases, the reaction can be carried out in the presence of a catalyst.
  • the solvent used may be inert to the reaction, such as water, lower alcohols such as methanol and ethanol, diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane and the like.
  • Ethers aromatic hydrocarbons such as benzene, xylene and toluene, aliphatic hydrocarbons such as pentane, hexane and cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane, N, N—
  • amides such as dimethylformamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone, dimethyl sulfoxide or a mixed solvent thereof.
  • Preferred examples include tetrahydrofuran, N, N-dimethylformamide, N-methylpyrrolidone, and mixtures thereof.
  • the equivalent of sodium hydrosulfide can be used in the range of 0.5 to 50 equivalents relative to compound (1-6), and preferably in the range of 1 to 20 equivalents.
  • the reaction can be carried out in the presence of a catalyst.
  • the catalyst examples include magnesium chloride.
  • the equivalent of the catalyst can be used in the range of 0.005 to 20 equivalents relative to compound (1-6), and preferably in the range of 0.01 to 5 equivalents.
  • the reaction temperature can be arbitrarily set from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and the range of 0 ° C. to the reflux temperature of the reaction mixture is preferable.
  • the reaction time varies depending on the concentration of the reaction substrate and the reaction temperature, but can usually be arbitrarily set in the range of 5 minutes to 100 hours, and preferably in the range of 1 hour to 48 hours.
  • the compound represented by the general formula (1-18) can be obtained from the reaction solution by ordinary post-treatment. For example, water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform are added to the reaction mixture for extraction, and then the organic layer is dried and concentrated to obtain the compound represented by the general formula (1-18). . When it becomes necessary to purify the compound, it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • reaction Formula 1 (In the formula, L 1 represents a good leaving group such as a chlorine atom, a bromine atom, and an iodine atom, and R 1 , R 2 and Het have the same meaning as described above.)
  • the compound represented by the general formula (5) is obtained by, for example, reacting the compound represented by the general formula (6) with the compound represented by the general formula (7) in a solvent or without a solvent in the presence of a base. Can be obtained.
  • the solvent used may be inert to the reaction.
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, and aromatics such as benzene, xylene, and toluene.
  • Hydrocarbons aliphatic hydrocarbons such as pentane, hexane and cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane, nitriles such as acetonitrile and propionitrile, N, N-dimethyl
  • amides such as formamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone, dimethyl sulfoxide or a mixed solvent thereof.
  • acetonitrile, propionitrile, tetrahydrofuran, and a mixture thereof can be used.
  • Examples of the base that can be used include triethylamine, diisopropylethylamine, tributylamine, 4-dimethylaminopyridine, pyridine, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-diazabicyclo [5. 4.0] -7-undecene (DBU) or 1,5-diazabicyclo [4.3.0] -5-nonene (DBN) and other organic bases, sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.
  • DABCO 1,4-diazabicyclo [2.2.2] octane
  • DBU 1,8-diazabicyclo [5. 4.0] -7-undecene
  • DBN 1,5-diazabicyclo [4.3.0] -5-nonene
  • other organic bases sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc
  • Inorganic bases such as alkali metal alcoholates, sodium hydride, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium hydroxide or potassium hydroxide.
  • triethylamine, diisopropylethylamine, pyridine and the like are mentioned.
  • As an equivalent of a base it can use in the range of 1-20 equivalent with respect to a compound (7), and the range of 1-5 equivalent is preferable.
  • the reaction temperature can be from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and preferably from 0 ° C. to the reflux temperature of the reaction mixture.
  • the reaction time can be 5 minutes to 100 hours, and preferably 1 hour to 48 hours.
  • compound (7) can be used in the range of 0.5 to 20 equivalents relative to compound (6), and preferably in the range of 0.5 to 5 equivalents.
  • the compound represented by the general formula (5) can be obtained from the reaction solution by ordinary post-treatment. For example, water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform are added to the reaction mixture for extraction, and then the organic layer is dried and concentrated to give compound (5). When it becomes necessary to purify the compound, it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • a reaction mixture can also be used for the manufacturing process 2 as it is, without post-processing.
  • Some of the compounds represented by the general formula (6) in Production Process 1 are known compounds, and some of them are available as commercial products. Others can also be easily produced according to known methods described in the literature, for example, methods described in International Publication No. 2010/036553.
  • the compound represented by the general formula (4) can be obtained, for example, by reacting the compound represented by the general formula (5) with a base in a solvent or without a solvent.
  • the solvent used may be inert to the reaction.
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, and aromatics such as benzene, xylene, and toluene.
  • Hydrocarbons aliphatic hydrocarbons such as pentane, hexane and cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane, nitriles such as acetonitrile and propionitrile, N, N-dimethyl
  • amides such as formamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone, dimethyl sulfoxide or a mixed solvent thereof.
  • acetonitrile, propionitrile, tetrahydrofuran, and a mixture thereof can be used.
  • Examples of the base that can be used include triethylamine, diisopropylethylamine, tributylamine, 4-dimethylaminopyridine, pyridine, 1,4-diazabicyclo [2.2.2] octane (DABCO), 1,8-diazabicyclo [5. 4.0] -7-undecene (DBU) or 1,5-diazabicyclo [4.3.0] -5-nonene (DBN) and other organic bases, sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc.
  • DABCO 1,4-diazabicyclo [2.2.2] octane
  • DBU 1,8-diazabicyclo [5. 4.0] -7-undecene
  • DBN 1,5-diazabicyclo [4.3.0] -5-nonene
  • other organic bases sodium methoxide, sodium ethoxide, potassium tert-butoxide, etc
  • Inorganic bases such as alkali metal alcoholates, sodium hydride, sodium hydrogen carbonate, potassium carbonate, cesium carbonate, sodium hydroxide or potassium hydroxide.
  • DABCO 1,4-diazabicyclo [2.2.2] octane
  • DBU 1,8-diazabicyclo [5.4.0] -7-undecene
  • DBN 1,5-diazabicyclo [4.3.0] ] -5-nonene
  • the reaction temperature can be from ⁇ 80 ° C.
  • the reaction mixture can be used as it is in the production step 3 without post-treatment.
  • the compound represented by the general formula (3) can be obtained, for example, by reacting the compound represented by the general formula (4) with an oxidizing agent in a solvent or without a solvent.
  • the solvent used may be inert to the reaction.
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, and aromatics such as benzene, xylene, and toluene.
  • Hydrocarbons aliphatic hydrocarbons such as pentane, hexane and cyclohexane, halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane, nitriles such as acetonitrile and propionitrile, N, N-dimethyl
  • amides such as formamide, N, N-dimethylacetamide, N-methylpyrrolidone, N, N′-dimethylimidazolidinone, dimethyl sulfoxide or a mixed solvent thereof.
  • acetonitrile, propionitrile, tetrahydrofuran, and a mixture thereof can be used.
  • the oxidizing agent examples include a mixed gas containing oxygen or oxygen gas.
  • the reaction temperature can be from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and preferably from 0 ° C. to the reflux temperature of the reaction mixture.
  • the reaction time can be 5 minutes to 100 hours, and preferably 1 hour to 48 hours.
  • the compound represented by the general formula (3) can be obtained from the reaction solution by ordinary post-treatment. For example, water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform are added to the reaction mixture for extraction, and then the organic layer is dried and concentrated to give compound (3). When it becomes necessary to purify the compound, it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • the compound represented by the general formula (2) can be obtained, for example, by reacting the compound represented by the general formula (3) with hydrazine in a solvent or without a solvent.
  • the solvent used may be inert to the reaction, such as methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, s-butyl alcohol or tert-butyl alcohol.
  • ethers such as diethyl ether, tetrahydrofuran, 1,4-dioxane and 1,2-dimethoxyethane
  • aromatic hydrocarbons such as benzene, xylene and toluene
  • aliphatic carbonization such as pentane, hexane and cyclohexane
  • halogenated hydrocarbons such as dichloromethane, chloroform and 1,2-dichloroethane
  • nitriles such as acetonitrile and propionitrile, N, N-dimethylformamide, N, N-dimethylacetamide, N-methyl Pyrrolidone, N, N'-dimethyl imidazolidinone amides, dimethyl sulfoxide or a mixed solvent thereof.
  • Preferable examples include methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, s-butyl alcohol, 1,2-dimethoxyethane, tetrahydrofuran, and mixtures thereof.
  • Examples of hydrazine that can be used include hydrazine monohydrate. As an equivalent of a hydrazine, it can use in the range of 1-20 equivalent with respect to a compound (3), and the range of 1-5 equivalent is preferable.
  • the reaction temperature can be from ⁇ 80 ° C. to the reflux temperature of the reaction mixture, and preferably from 0 ° C. to the reflux temperature of the reaction mixture.
  • the reaction time can be 5 minutes to 100 hours, and preferably 1 hour to 48 hours.
  • the compound represented by the general formula (2) can be obtained from the reaction solution by ordinary post-treatment.
  • the compound (2) can be obtained by concentrating the reaction mixture.
  • a compound (2) can be obtained by adding a solvent such as n-hexane, diisopropyl ether or chloroform to the reaction mixture as necessary, and collecting the precipitated solid by filtration. Further, for example, water and an extraction solvent such as toluene, ethyl acetate, diethyl ether or chloroform are added to the reaction mixture for extraction, and then the organic layer is dried and concentrated to obtain compound (2).
  • it becomes necessary to purify the compound it can be separated and purified by any purification method such as recrystallization or column chromatography.
  • the compound represented by the general formula (7) used in the production step 1 can be produced, for example, according to the route represented by the following reaction formula.
  • reaction Formula 2 (Wherein L 2 represents a good leaving group such as a fluorine atom, chlorine atom, bromine atom, etc., R 4 represents a C 1 -C 4 alkyl group such as methyl, ethyl, etc., and Het is the same as above. Represents meaning.)
  • the compound represented by the general formula (9) is represented by the general formula (8) by reacting the compound represented by the general formula (9) with a malonic acid diester (22) according to a known method described in the literature, for example, a method described in International Publication No. 2007/066661. Can be produced.
  • the compound represented by the general formula (7) can be manufactured.
  • Some of the compounds represented by the general formula (9) used here are known compounds, and some of them are available as commercial products. Others can also be easily produced according to the synthesis methods of general known compounds described in the literature.
  • the compound represented by the general formula (7) used in the production step 1 can be produced, for example, according to the route represented by the following reaction formula.
  • reaction Formula 3 (Wherein R 4 represents a C 1 -C 4 alkyl group such as methyl, ethyl, etc., and Het has the same meaning as described above.)
  • R 4 represents a C 1 -C 4 alkyl group such as methyl, ethyl, etc., and Het has the same meaning as described above.
  • a compound represented by the general formula (7) is produced by reacting the compound represented by the general formula (10) according to a known method described in the literature, for example, a method described in US Patent Application Publication No. 2007/0015752. be able to.
  • a substituent described as Me represents a methyl group
  • Et represents an ethyl group
  • n-Pr and Pr-n represent normal propyl groups
  • i-Pr and Pr-i Is an isopropyl group
  • s-Bu and Bu-s are secondary butyl groups
  • i-Bu and Bu-i are isobutyl groups
  • t-Bu and Bu-t are A tertiary butyl group
  • CN and NC each represent a cyano group
  • Ph represents a phenyl group
  • Bn represents a benzyl group
  • Ac represents an acetyl group
  • represents a double bond
  • ⁇ represents a triple bond.
  • “-” means unsubstituted.
  • the compound of the present invention When the compound of the present invention is applied as a plant disease or plant pest control agent, it is usually mixed with a suitable solid carrier or liquid carrier, and if desired, a surfactant, penetrant, spreading agent, thickener, antifreeze agent. , Binders, anti-caking agents, disintegrants, anti-decomposition agents, etc., added, liquid concentrate (emulsifiable concentrate), emulsion (emulsible concentrate), wettable powder (wettable powder), water solvent (water soluble powder), granule Water dispersible granule, water soluble granule, suspension concentrate, emulsion (suspension concentrate), suspension Marujon (suspoemulsion), microemulsion (microemulsion), dusts (dustable powder), can be put into practical use in granules (granule) and gels (gel) like any dosage form of the formulation.
  • a surfactant penetrant
  • thickener thickener
  • antifreeze agent Bin
  • solid carriers examples include quartz, kaolinite, pyrophyllite, sericite, talc, bentonite, acid clay, attapulgite, zeolite, and diatomaceous earth, and other minerals such as calcium carbonate, ammonium sulfate, sodium sulfate, and potassium chloride.
  • examples include salts, synthetic silicic acid and synthetic silicates.
  • liquid carrier examples include alcohols such as ethylene glycol, propylene glycol and isopropanol, aromatic hydrocarbons such as xylene, alkylbenzene and alkylnaphthalene, ethers such as butyl cellosolve, ketones such as cyclohexanone, and esters such as ⁇ -butyrolactone. And acid amides such as N-methylpyrrolidone and N-octylpyrrolidone, vegetable oils such as soybean oil, rapeseed oil, cottonseed oil and castor oil, and water. These solid and liquid carriers may be used alone or in combination of two or more.
  • surfactant examples include polyoxyethylene alkyl ether, polyoxyethylene alkyl aryl ether, polyoxyethylene styryl phenyl ether, polyoxyethylene polyoxypropylene block copolymer, polyoxyethylene fatty acid ester, sorbitan fatty acid ester and polyoxyethylene sorbitan Nonionic surfactant such as fatty acid ester, alkyl sulfate, alkylbenzene sulfonate, lignin sulfonate, alkyl sulfosuccinate, naphthalene sulfonate, alkyl naphthalene sulfonate, salt of formalin condensate of naphthalene sulfonate, Salt of formalin condensate of alkyl naphthalene sulfonic acid, polyoxyethylene alkylaryl ether sulfate and phosphate, polyoxyethylene polystyrene Anionic surfactants such as
  • the compound of the present invention when used as an agrochemical, other types of herbicides, various insecticides, acaricides, nematicides, fungicides, plant growth regulators, co-agents, and the like can be used at the time of formulation or spraying. You may mix and apply it with a power agent, a fertilizer, a soil conditioner, etc. In particular, by applying it in combination with other agricultural chemicals or plant hormones, it can be expected to reduce costs by reducing the amount of applied medicine, expand the bactericidal insecticidal spectrum due to the synergistic action of the mixed drugs, and higher pest control effects. At this time, a combination with a plurality of known agricultural chemicals is also possible. Examples of the type of agrochemical used in combination with the compound of the present invention include compounds described in the 1999 edition of Farm Chemicals Handbook (Farm Chemicals Handbook). Specific examples of common names are as follows, but the general names are not necessarily limited to these.
  • the dosage of the compound of the present invention varies depending on the application scene, application timing, application method, cultivated crops, etc., but generally the amount of the active ingredient is suitably about 0.005 to 50 kg per hectare (ha).
  • [Wettable powder] Compound of the present invention 0.1 to 80 parts Solid carrier 5 to 98.9 parts Surfactant 1 to 10 parts Others 0 to 5 parts Others include, for example, anti-caking agent, decomposition inhibitor and the like.
  • Liquid Compound of the present invention 0.01 to 70 parts Liquid carrier 20 to 99.99 parts Others 0 to 10 parts Others include, for example, antifreezing agents and spreading agents.
  • the above preparation is sprayed with water diluted 1 to 10,000 times or without dilution.
  • Emulsion Compound No. 1 of the present invention A-1 20 parts Methylnaphthalene 55 parts Cyclohexanone 20 parts Solpol 2680 5 parts (Mixture of nonionic surfactant and anionic surfactant: Toho Chemical Co., Ltd. trade name) The above is uniformly mixed to obtain an emulsion. In use, the emulsion is diluted 50 to 20000 times and sprayed so that the amount of the active ingredient is 0.005 to 50 kg per hectare.
  • the above ingredients except the active ingredient are uniformly dissolved, and then the compound of the present invention is added and stirred well, followed by wet grinding with a sand mill to obtain a flowable agent.
  • the flowable agent is diluted 50 to 20000 times and sprayed so that the amount of the active ingredient is 0.005 to 50 kg per hectare.
  • the application method of the compound of the present invention includes foliage spraying, soil treatment, seed disinfection and the like, but it is also effective in general methods usually used by those skilled in the art.
  • the reaction solution was extracted with ethyl acetate (50 ml ⁇ 1 time).
  • the obtained organic layer was washed with water, dried over sodium sulfate, and the solvent was distilled off under reduced pressure.
  • reaction solution was extracted with ethyl acetate (50 ml ⁇ 1 time).
  • the obtained organic layer was washed with water, dried over sodium sulfate, and the solvent was distilled off under reduced pressure.
  • reaction solution was extracted with ethyl acetate (50 ml ⁇ 1 time).
  • the obtained organic layer was washed with water, dried over sodium sulfate, and the solvent was distilled off under reduced pressure.
  • reaction mixture was cooled to room temperature and 0.03 g (0.22 mmol) of N-chlorosuccinimide was added.
  • the reaction solution was stirred at room temperature for 2 days, and then stirred at 50 ° C. for 3 hours. After the completion of the reaction, the reaction mixture was allowed to cool, and succinimide precipitated in the reaction mixture was filtered off. The solvent of the obtained filtrate was distilled off under reduced pressure.
  • Step 2 3-chloro-4- (3-chloro-5-methoxypyridin-2-yl) -5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazine (Compound No. A- Synthesis of 75)
  • 0.31 g of the target product was obtained as white crystals from 0.42 g (0.90 mmol) of the target product in Step 1. Melting point: 171-172 ° C
  • the obtained organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution, dehydrated and dried in the order of saturated brine and then anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.
  • the obtained organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution, dehydrated and dried in the order of saturated brine and then anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.
  • the reaction mixture was allowed to cool, and then iron powder in the reaction mixture and salts generated by the reaction were separated by filtration.
  • the obtained filtrate was diluted with 50 ml of ethyl acetate, washed with water, dried over magnesium sulfate, and the solvent was distilled off under reduced pressure.
  • Step 1 Synthesis of 4- (5-butoxy-3-chloropyridin-2-yl) -5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazin-3 (2H) -one n -0.31 g (4.23 mmol) of butanol, 0.16 g of 63 wt% sodium hydride (4.23 mmol, dispersed in mineral oil) and 5 ml of tetrahydrofuran were mixed under ice cooling and then stirred at room temperature for 30 minutes. . After completion of the stirring, the solvent of the reaction mixture was distilled off under reduced pressure to obtain crude sodium n-butoxide.
  • the obtained organic layer was washed with water, dehydrated and dried in the order of saturated brine and anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.
  • Step 2 Synthesis of 4- (5-butoxy-3-chloropyridin-2-yl) -3-chloro-5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazine
  • Step 1 of 4- (3-Chloro-5- (methylthio) pyridin-2-yl) -5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazin-3 (2H) -one Synthesis 4- (3,5-dichloropyridin-2-yl) -5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazin-3 (2H) -one 1.50 g (3.18 mmol) ), 0.67 g (9.53 mmol) of sodium thiomethoxide and 5 ml of dimethyl sulfoxide were mixed under ice-cooling, followed by stirring at 0 ° C.
  • Step 2 Synthesis of 3-chloro-4- (3-chloro-5- (methylthio) pyridin-2-yl) -5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazine Synthesis Example 4- (3-Chloro-5- (methylthio) pyridin-2-yl) -5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazine-3 (2H ) -On 1.41 g (2.92 mmol), 1.33 g of the desired product was obtained as white crystals. Melting point: 149-151 ° C
  • Step 1 Synthesis of 2- (2-fluorophenyl) -N-methoxy-N-methylacetamide 5.00 g (32.4 mmol) of 2- (2-fluorophenyl) acetic acid, 4.11 g (32.4 mmol) of oxalyl chloride , N, N-dimethylformamide (0.022 g, 0.30 mmol) and methylene chloride (50 ml) were mixed under ice-cooling, followed by stirring at room temperature for 17 hours. After completion of the reaction, the solvent in the reaction mixture was distilled off under reduced pressure to obtain crude chloride 2- (2-fluorophenyl) acetic acid.
  • Step 2 Synthesis of 2- (2-fluorophenyl) -1- (5-methoxythiophen-2-yl) ethanone
  • a mixed solution of 1.00 g (8.76 mmol) of 2-methoxythiophene and 10 ml of tetrahydrofuran was cooled to 0 ° C.
  • 5.4 ml (8.76 mmol) of a tetrahydrofuran solution (1.63 mol / L) of n-butyllithium was added dropwise, followed by stirring for 1 hour.
  • Step 3 Synthesis of 2-bromo-2- (2-fluorophenyl) -1- (5-methoxythiophen-2-yl) ethanone 2- (2-fluorophenyl) -1- (5-methoxythiophene-2- Yl)
  • a mixed solution of 0.67 g (2.68 mmol) of ethanone, 1.32 g (5.90 mmol) of cupric bromide, 10 ml of ethyl acetate and 10 ml of chloroform was stirred with heating under reflux for 2 hours. After completion of the stirring, the reaction mixture was allowed to cool, and cupric bromide and the salt produced by the reaction in the reaction mixture were separated by filtration. The obtained filtrate was washed with water and dried over sodium sulfate, and then the solvent was distilled off under reduced pressure to obtain 0.88 g of the desired product as a brown oil.
  • Step 4 Synthesis of 4- (3,5-dichloropyridin-2-yl) -6- (2-fluorophenyl) -5- (5-methoxythiophen-2-yl) pyridazin-3 (2H) -one Reference
  • Step 5 Synthesis of 3-chloro-4- (3,5-dichloropyridin-2-yl) -6- (2-fluorophenyl) -5- (5-methoxythiophen-2-yl) pyridazine
  • Step 2 Synthesis of 4- (3-chloro-5-hydroxypyridin-2-yl) -5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazin-3 (2H) -one 4 -(5- (benzyloxy) -3-chloropyridin-2-yl) -5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazin-3 (2H) -one 3.0 g ( (5.52 mmol) A mixed solution of 1.2 g of 10% by weight palladium carbon (containing about 50% by weight of water), 5 ml of acetic acid and 100 ml of methanol was stirred at room temperature for 21 hours in a hydrogen atmosphere. After completion of the stirring, palladium carbon in the reaction mixture was filtered off. From the obtained filtrate, the solvent was distilled off under reduced pressure to obtain 2.0 g of the desired product as crystals.
  • Step 3 Synthesis of 5-chloro-6- (3-chloro-5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazin-4-yl) pyridin-3-ol
  • Step 4 Synthesis of 3-chloro-4- (3-chloro-5- (methoxymethoxy) pyridin-2-yl) -5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazine 5 -Chloro-6- (3-chloro-5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazin-4-yl) pyridin-3-ol 0.35 g (0.74 mmol), chloro A mixed solution of 0.18 g (2.22 mmol) of (methoxy) methane, 0.72 g (2.22 mmol) of cesium carbonate and 6 ml of acetonitrile was stirred with heating under reflux for 6 hours.
  • A-261) 4- (3,5-dichloropyridin-2-yl) -5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazine-3-carbonitrile 0.05 g (0.10 mmol), 30 A mixed solution of 0.02 g (0.11 mmol) of a weight% aqueous sodium hydroxide solution, 0.02 g (0.20 mmol) of 30 wt% aqueous hydrogen peroxide, 0.2 ml of dimethyl sulfoxide and 2 ml of methanol was stirred at room temperature for 3 hours. did. After completion of the stirring, 20 ml of water was added to stop the reaction, and then crystals precipitated in the reaction solution were collected by filtration to obtain 0.04 g of the objective product as white crystals. Melting point: 197-200 ° C
  • Step 1 Synthesis of 2- (3,5-dichloropyridin-2-yl) acetic acid 57.8 g (0.36 mol) of diethyl malonate, 30.0 g (0.16 mol) of 2,3,5-trichloropyridine, carbonic acid A mixed solution of 117.6 g (0.36 mol) of cesium and 200 ml of dimethyl sulfoxide was heated and stirred at 110 ° C. for 9 hours. After completion of the stirring, the reaction mixture was allowed to cool, water was added, and the mixture was extracted with ethyl acetate (400 ml ⁇ 1).
  • the obtained organic layer was washed with water, dehydrated and dried in the order of saturated brine and then anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure.
  • the resulting mixed solution of crude diethyl (3,5-dichloropyridin-2-yl) malonate, sodium hydroxide 32.8 g (0.82 mol), ethanol 200 ml and water 100 ml was heated and stirred at 60 ° C. for 2 hours. did.
  • the reaction mixture was cooled to 10 ° C. and concentrated hydrochloric acid was added to adjust the pH to 3-4. After stirring at room temperature for 2 hours, crystals precipitated in the reaction solution were collected by filtration to obtain 17.9 g of the desired product as white crystals.
  • Step 2 Synthesis of 5- (4-chlorophenyl) -4- (3,5-dichloropyridin-2-yl) -6- (2-fluorophenyl) pyridazin-3 (2H) -one 2- (3,5 -Dichloropyridin-2-yl) acetic acid 0.76 g (3.69 mmol), 2-bromo-1- (4-chlorophenyl) -2- (2-fluorophenyl) ethanone 1.21 g (3.69 mmol), triethylamine 0 A mixed solution of .63 g (6.27 mmol) and 10 ml of acetonitrile was stirred at room temperature for 3 hours.
  • Step 1 Synthesis of 2- (2-chloropyridin-3-yl) acetic acid 1.91 g (13.5 mmol) of 2-chloro-nicotinaldehyde, 1.68 g (13.5 mmol) of methyl (methylsulfinyl) methyl sulfide (FAMSO) ), A mixed solution of 1.7 ml of a 40 wt% methanol solution of benzyltrimethylammonium hydroxide and 10 ml of tetrahydrofuran was stirred with heating at 60 ° C. for 2 hours.
  • 2- (2-chloropyridin-3-yl) acetic acid 1.91 g (13.5 mmol) of 2-chloro-nicotinaldehyde, 1.68 g (13.5 mmol) of methyl (methylsulfinyl) methyl sulfide (FAMSO) ), A mixed solution of 1.7 ml of a 40 wt% methanol solution of benzyl
  • the obtained aqueous layer was washed with chloroform (120 ml ⁇ 1). Further, concentrated hydrochloric acid was added to adjust the pH to 3 to 4, and the crystals precipitated in the aqueous layer were collected by filtration to obtain 0.56 g of the desired product as white crystals.
  • Step 2 Synthesis of 4- (2-chloropyridin-3-yl) -5- (3,5-dimethoxyphenyl) -6- (2-fluorophenyl) pyridazin-3 (2H) -one Step of Reference Example 1 By the method according to 2, 1.00 g of the desired product was obtained as white crystals.
  • the compound of the present invention can be synthesized according to the above synthesis examples.
  • or the synthesis example 36 is shown in Table 10 thru
  • “Me” represents a methyl group
  • Et represents an ethyl group
  • n-Pr represents a normal propyl group
  • i-Pr represents an isopropyl group
  • n-Bu represents a normal butyl group
  • NC represents a cyano group
  • Ph represents a phenyl group
  • Bn represents a benzyl group
  • Ac represents an acetyl group
  • represents a double bond
  • ⁇ represents a triple bond.
  • * 1 means “resinous”.
  • * 2 means a mixture of two or more diastereomers generated by limited bond rotation due to steric hindrance between substituents.
  • “-” means unsubstituted.
  • test Example Next, the usefulness of the fungicide of the present invention will be specifically described in the following test examples, but the present invention is not limited to these.
  • Test Example 1 Wheat Fusarium Control Effect Test 1.3 In a 90 cm 3 plastic pot planted with wheat (variety: Haruyutaka) at the leaf stage, 5 ml of a drug solution prepared by diluting the compound emulsion of the present invention with water and adjusting to 500 ppm Scattered. One day after spraying, a conidial spore suspension of wheat blight fungus (Septoria nodorum) was spray-inoculated on wheat and placed in an inoculation box at a temperature of 20 ° C. and a humidity of 100% for 2 days. Thereafter, it was placed in an air-conditioned greenhouse (20 ° C.) and held for 6 days. The ratio of the formed lesions to the inoculated leaves was measured, and the control value was calculated according to the following formula.
  • Control value [1- (treatment area lesion area ratio / untreated area lesion area ratio)] x 100
  • Test Example 2 Wheat Red Rust Control Effect Test 1.3 A chemical solution prepared by diluting the compound emulsion of the present invention with water in a 90 cm 3 plastic pot planted with wheat (variety: Norin 61) at 500 leaves was prepared. 5 ml sprayed. One day after spraying, a spore suspension of wheat red rust fungus (Puccinia recondita) was spray-inoculated into wheat and placed in an inoculation box at a temperature of 20 ° C. and a humidity of 100% for 1 day. Thereafter, it was placed in an air-conditioned greenhouse (20 ° C.) and held for 8 days. The ratio of the formed lesions to the inoculated leaves was measured, and the control value was calculated from the same calculation formula as in Test Example 1.
  • Test Example 3 Wheat powdery mildew control effect test 1.3 Chemical solution prepared by diluting the compound emulsion of the present invention with water in a 90 cm 3 plastic pot planted with wheat (variety: Norin 61) at the leaf stage 5 ml was sprayed. One day after spraying, wheat was placed in an air-conditioned greenhouse (20 ° C.), and wheat was inoculated with conidia of wheat powdery mildew (Blumeria graminis). Thereafter, it was held for 7 days, the ratio of the formed lesions to the inoculated leaves was measured, and the control value was calculated from the same formula as in Test 1.
  • Test Example 4 Cucumber Gray Mold Control Effect Test
  • Cucumber (variety: Sagamihanjiro) was planted in a 90 cm 3 plastic pot, the compound emulsion of the present invention was diluted with water at the cotyledon stage, and 5 ml of chemical solution prepared to 500 ppm was sprayed. After air drying, the treated leaves were cut and placed in a plastic container.
  • a conidial spore suspension of cucumber gray mold fungus (Botrytis cinerea) and a dissolved PDA medium were mixed at a ratio of 1: 1, and 30 ⁇ l of the treated leaves were inoculated dropwise. After inoculation, after placing it at 20 ° C. under high humidity for 3 days, the ratio of the formed lesions to the inoculated leaves was measured, and the control value was calculated from the same formula as in Test 1.
  • Test Example 5 Cucumber powdery mildew control effect test Cucumber (variety: Sagamihanjiro) was planted in a 90 cm 3 plastic pot, the compound emulsion of the present invention was diluted with water at the cotyledon stage, and 5 ml of chemical solution prepared to 500 ppm was sprayed. did. After air drying, the cucumber was placed in an air-conditioned greenhouse (20 ° C.) and sprayed with a conidial spore suspension of cucumber powdery mildew (Erysiphe polygoni). After 9 days, the ratio of the formed lesions to the inoculated leaves was measured, and the control value was calculated from the same formula as in Test 1.
  • Test Example 6 Antifungal activity measurement test Add 1 ml of sterilized water to a sterilized test tube, drop a part of the water into a petri dish with black koji mold, and place the upper part on a flat surface of a bent Pasteur pipette. Aspergillus niger spores were collected by mixing with rubbing water. Water containing spore of black koji mold was returned to the test tube and mixed well to prepare a black koji mold spore solution, and the number of spores was counted under a microscope.
  • Test Example 7 Anti-Internal Parasite Measurement Test Eggs of torsion stomachworms (Haemonchus contourtus) were collected and sterilized by the following method from goat feces by sucrose density gradient centrifugation. 100 g of goat feces was stirred in 100 ml of distilled water and filtered with gauze. The filtrate was centrifuged at 1500 g for 5 minutes, 100 ml of a 50 wt% sucrose aqueous solution was added to the resulting precipitate and stirred for 30 minutes, and then again centrifuged at 1500 g for 5 minutes. The supernatant was filtered through a 30 ⁇ m stainless steel net and collected.
  • the obtained egg was sterilized by immersing it in a 7% by weight aqueous sodium hypochlorite solution for 5 minutes, and washed with sterilized water to obtain a disinfected egg of a torsion stomachworm.
  • a potato dextrose agar medium (containing 1% agar) dissolved in a 96-well plate was dispensed at 60 ⁇ l per well, and then 30 ⁇ l of sterilized water containing eggs was added per well. The number of eggs was 100 per well. From this, 10 ⁇ l of a chemical solution prepared by dissolving the compound of the present invention in dimethyl sulfoxide (DMSO) to a final concentration of 100 ppm was added. It was allowed to stand at 25 ° C. for 7 days under dark conditions. The number of torsional stomach worms alive after hatching (number of surviving worms after hatching) was measured, and the inactivity rate for the untreated area was calculated according to the following formula.
  • Inactivity rate (%) [1-(number of live worms after hatching / number of live worms after hatching in untreated area)] x 100
  • the substituted pyridazine compound of the present invention is a novel compound, exhibits an excellent agricultural and horticultural bactericidal action, and does not show any phytotoxicity against useful crops.

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Abstract

La présente invention a pour but de proposer un composé représenté par la formule (1), lequel est utile comme agent bactéricide, en particulier un agent bactéricide agricole ou horticole. (Dans la formule, Het représente n'importe quel groupe choisi parmi D1-1 à D1-3 ; R1 et R2 représentent indépendamment n'importe quel groupe choisi parmi G-1 à G-5 ; et R3 représente un atome d'hydrogène, un atome d'halogène, un groupe alkyle en C1-C6 ou similaires).
PCT/JP2012/062851 2011-05-20 2012-05-18 Composé pyridazine substitué et agent bactéricide agricole ou horticole WO2012161133A1 (fr)

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Cited By (7)

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JP2013542267A (ja) * 2010-11-15 2013-11-21 エージンバイオ， インコーポレイテッド 認知障害を処置するためのピリダジン誘導体、組成物、および方法
US10329301B2 (en) 2013-12-20 2019-06-25 Agenebio, Inc. Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
CN110551637A (zh) * 2019-09-03 2019-12-10 黑龙江省农业科学院植物保护研究所 一种来自黄芪根部的高效抑制番茄灰霉病菌的棘壳孢菌及其应用
US10815242B2 (en) 2015-06-19 2020-10-27 Agenebio, Inc. Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
CN114145197A (zh) * 2021-09-26 2022-03-08 中国科学院合肥物质科学研究院 一种提高小麦对赤霉病抗性的方法
US11414425B2 (en) 2018-06-19 2022-08-16 Agenebio, Inc. Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
US11505555B2 (en) 2016-12-19 2022-11-22 Agenebio, Inc. Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment

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WO2007066601A1 (fr) * 2005-12-07 2007-06-14 Sumitomo Chemical Company, Limited Compose de pyridazine et son emploi
WO2009090039A1 (fr) * 2008-01-16 2009-07-23 Syngenta Participations Ag Fungicides à base de pyridazine
WO2010036553A1 (fr) * 2008-09-24 2010-04-01 E. I. Du Pont De Nemours And Company Pyridazines fongicides
WO2011017261A1 (fr) * 2009-08-07 2011-02-10 E. I. Du Pont De Nemours And Company Pyridazines fongicides substituées par un diphényle

Patent Citations (4)

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Publication number Priority date Publication date Assignee Title
WO2007066601A1 (fr) * 2005-12-07 2007-06-14 Sumitomo Chemical Company, Limited Compose de pyridazine et son emploi
WO2009090039A1 (fr) * 2008-01-16 2009-07-23 Syngenta Participations Ag Fungicides à base de pyridazine
WO2010036553A1 (fr) * 2008-09-24 2010-04-01 E. I. Du Pont De Nemours And Company Pyridazines fongicides
WO2011017261A1 (fr) * 2009-08-07 2011-02-10 E. I. Du Pont De Nemours And Company Pyridazines fongicides substituées par un diphényle

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2013542267A (ja) * 2010-11-15 2013-11-21 エージンバイオ， インコーポレイテッド 認知障害を処置するためのピリダジン誘導体、組成物、および方法
US9801879B2 (en) 2010-11-15 2017-10-31 Agenebio, Inc. Pyridazine derivatives, compositions and methods for treating cognitive impairment
US10329301B2 (en) 2013-12-20 2019-06-25 Agenebio, Inc. Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
US11142529B2 (en) 2013-12-20 2021-10-12 Agenebio, Inc. Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
US10815242B2 (en) 2015-06-19 2020-10-27 Agenebio, Inc. Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
US11312721B2 (en) 2015-06-19 2022-04-26 Agenebio, Inc. Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
US11505555B2 (en) 2016-12-19 2022-11-22 Agenebio, Inc. Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
US11414425B2 (en) 2018-06-19 2022-08-16 Agenebio, Inc. Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment
CN110551637A (zh) * 2019-09-03 2019-12-10 黑龙江省农业科学院植物保护研究所 一种来自黄芪根部的高效抑制番茄灰霉病菌的棘壳孢菌及其应用
CN110551637B (zh) * 2019-09-03 2020-11-27 黑龙江省农业科学院植物保护研究所 一种来自黄芪根部的高效抑制番茄灰霉病菌的棘壳孢菌及其应用
CN114145197A (zh) * 2021-09-26 2022-03-08 中国科学院合肥物质科学研究院 一种提高小麦对赤霉病抗性的方法

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