WO2009110542A1 - Anilide compound and use thereof - Google Patents

Anilide compound and use thereof Download PDF

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Publication number
WO2009110542A1
WO2009110542A1 PCT/JP2009/054154 JP2009054154W WO2009110542A1 WO 2009110542 A1 WO2009110542 A1 WO 2009110542A1 JP 2009054154 W JP2009054154 W JP 2009054154W WO 2009110542 A1 WO2009110542 A1 WO 2009110542A1
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Prior art keywords
group
carboxylic acid
quinoline
compound
anilide
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PCT/JP2009/054154
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French (fr)
Japanese (ja)
Inventor
裕史 阪口
岳 小森
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住友化学株式会社
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Publication of WO2009110542A1 publication Critical patent/WO2009110542A1/en

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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
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A01N43/42—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings condensed with carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

Definitions

  • the present invention relates to an anilide compound and its use for controlling plant diseases.
  • An object of the present invention is to provide a compound having an excellent control effect against plant diseases.
  • A represents a 6-quinolyl group, a benzothiazol-6-yl group or a [1,5] naphthyridin-2-yl group; n represents an integer of 0 to 4, R 1 represents a halogen atom or a C1-C3 alkyl group, R 2 represents a C1-C8 alkyl group, a C1-C8 alkoxy group, a C3-C9 alkenyloxy group, a C3-C9 alkynyloxy group, a C6-C10 aryloxy group substituted at the 3-position or 4-position of the benzene ring, or ( C3-C8 cycloalkyl) represents a C1-C6 alkoxy group.
  • the C1-C8 alkyl group, C1-C8 alkoxy group, C3-C9 alkenyloxy group, C3-C9 alkynyloxy group and (C3-C8 cycloalkyl) C1-C6 alkoxy group represented by R 2 are halogenated. May be substituted with one or more groups selected from the group consisting of atoms and C1-C3 alkoxy groups,
  • the C6-C10 aryloxy group represented by R 2 is substituted with one or more groups selected from the group consisting of a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group and a trifluoromethyl group.
  • A represents a benzothiazol-6-yl group or a [1,5] naphthyridin-2-yl group.
  • R 1 is the same or different from each other.
  • the anilide compound shown below (it is hereafter described as this invention compound). [2] The anilide compound according to [1], wherein A is a 6-quinolyl group. [3] The anilide compound according to [1] or [2], wherein R 2 is substituted at the 3-position of the benzene ring.
  • A is a 6-quinolyl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a methoxy group substituted at the 3-position of the benzene ring
  • the anilide compound according to the above [5] 3 ′-(4-Pentynyloxy) -quinoline-6-carboxylic acid anilide. [6] 3′-Butyloxy-quinoline-6-carboxylic acid anilide. [7] 3 ′-(2-pentenyloxy) -quinoline-6-carboxylic acid anilide.
  • a plant disease control agent comprising the anilide compound according to any one of [1] to [18] (hereinafter referred to as the present invention control agent).
  • a method for controlling plant diseases comprising a step of applying an effective amount of the anilide compound according to any one of [1] to [18] to a plant or soil.
  • Examples of the halogen atom represented by R 1 include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
  • Examples of the C1-C3 alkyl group include a methyl group, an ethyl group, a propyl group, and an isopropyl group.
  • Examples of the C1-C8 alkoxy group represented by R 2 include methoxy group, ethoxy group, 1-methylethoxy group, propoxy group, 1-methylpropoxy group, 2-methylpropoxy group, butoxy group, 1-methylbutoxy group, 2-methylbutoxy group, 3-methylbutoxy group, 2,3-dimethylbutoxy group, pentyloxy group, 1-methylpentyloxy group, 2-methylpentyloxy group, 3-methylpentyloxy group, 4-methylpentyloxy group Group, hexyloxy group, heptyloxy group and octyloxy group.
  • Examples of the C3-C9 alkenyloxy group represented by R 2 include 2-propenyloxy group, 1-methyl-2-propenyloxy group, 2-methyl-2-propenyloxy group, 2-butenyloxy group, 3- Methyl-2-butenyloxy group, 3-butenyloxy group, 3-methyl-3-butenyloxy group, 2-pentenyloxy group, 3-pentenyloxy group, 4-pentenyloxy group, prenyloxy group, 4-methyl-4-pentenyl Oxy group, 4-methyl-3-pentenyloxy group, 2-hexenyloxy group, 3-hexenyloxy group, 4-hexenyloxy group, 5-hexenyloxy group, 2-heptenyloxy group, 3-heptenyloxy group, 4-heptenyloxy group Group, 5-heptenyloxy group, 6-heptenyloxy group, 2-octenyloxy group , 3-octenyloxy group, 4-octenyloxy group,
  • Examples of the C3-C9 alkynyloxy group represented by R 2 include 2-propynyloxy group, 2-butynyloxy group, 3-butynyloxy group, 2-pentynyloxy group, 3-pentynyloxy group, 4-pentynyloxy group, and the like.
  • Examples of the C6-C10 aryloxy group represented by R 2 include a phenoxy group and a naphthoxy group.
  • Examples of the (C3-C8 cycloalkyl) C1-C6 alkoxy group represented by R 2 include cyclopropylmethoxy group, cyclopropylethoxy group, cyclopropylpropoxy group, cyclopropylbutoxy group, cyclopropylpentyloxy group, cyclopropylhexyl.
  • the C1-C8 alkyl group, C1-C8 alkoxy group, C3-C9 alkenyloxy group, C3-C9 alkynyloxy group and (C3-C8 cycloalkyl) C1-C6 alkoxy group represented by R 2 are a halogen atom and C1-C3 It may be substituted with one or more groups selected from the group consisting of alkoxy groups.
  • the halogen atom in this case include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • Examples of the C1-C3 alkoxy group in this case include a methoxy group, an ethoxy group, a propoxy group, and an isopropoxy group.
  • the C6-C10 aryloxy group represented by R 2 may be substituted with one or more groups selected from the group consisting of a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group and a trifluoromethyl group.
  • Examples of the halogen atom in this case include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
  • Examples of the C1-C3 alkyl group in this case include a methyl group, an ethyl group, a propyl group, and an isopropyl group.
  • Examples of the C1-C3 alkoxy group in this case include a methoxy group, an ethoxy group, a propoxy group, and an isopropoxy group.
  • Examples of the C1-C8 alkyl group substituted with one or more groups selected from the group consisting of a halogen atom represented by R 2 and a C1-C3 alkoxy group include a fluoromethyl group, a difluoromethyl group, and a trifluoromethyl group.
  • Chloromethyl group dichloromethyl group, trichloromethyl group, bromomethyl group, 1-fluoroethyl group, 1-chloroethyl group, 1-bromoethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2, 2,2-trifluoroethyl group, pentafluoroethyl group, 1-trifluoromethyl-2,2,2-trifluoroethyl group, 3-fluoropropyl group, 3,3,3-trifluoropropyl group, 2, 2,3,3,3-pentafluoropropyl, 3-chloropropyl, 4-fluorobutyl, 4-chloro Robutyl group, 5-fluoropentyl group, 5-chloropentyl group, 6-fluorohexyl group, 6-chlorohexyl group, 7-fluoroheptyl group, 7-chloroheptyl group,
  • Examples of the C1-C8 alkoxy group substituted with one or more groups selected from the group consisting of a halogen atom represented by R 2 and a C1-C3 alkoxy group include a trifluoromethoxy group, a 1-fluoroethoxy group, 2 -Fluoroethoxy group, 2-chloroethoxy group, 2-bromoethoxy group, 2,2,2-trifluoroethoxy group, pentafluoroethoxy group, 1-trifluoromethyl-2,2,2-trifluoroethoxy group, 3-fluoropropoxy group, 3,3,3-trifluoropropoxy group, 2,2,3,3,3-pentafluoropropoxy group, 3-chloropropoxy group, 4-fluorobutoxy group, 4-chlorobutoxy group, 5-fluoropentyloxy group, 5-chloropentyloxy group, 6-fluorohexyloxy group, 6-chlorohexyl Oxy group, 7-fluorohept
  • Examples of the C3-C9 alkenyloxy group substituted with one or more groups selected from the group consisting of a halogen atom represented by R 2 and a C1-C3 alkoxy group include a 3,3-difluoro-2-propenyloxy group.
  • Examples of the C3-C9 alkynyloxy group substituted with one or more groups selected from the group consisting of a halogen atom represented by R 2 and a C1-C3 alkoxy group include a 4-chloro-2-butynyloxy group, 4- Bromo-2-butynyloxy group, 4-methoxy-2-butynyloxy group, 5-chloro-2-pentynyloxy group, 5-bromo-2-pentynyloxy group, 5-methoxy-2-pentynyloxy group, 5 -Chloro-3-pentynyloxy group, 5-bromo-3-pentynyloxy group, 5-methoxy-3-pentynyloxy group, 6-chloro-3-hexynyloxy group, 6-bromo-3-hexynyloxy group, 6-methoxy-3-hexynyloxy group, 6-chloro-4-hexynyloxy group, 6-bromo-4
  • Examples of the (C3-C8 cycloalkyl) C1-C6 alkoxy group substituted with one or more groups selected from the group consisting of a halogen atom represented by R 2 and a C1-C3 alkoxy group include (2,2- (Dichlorocyclopropyl) methoxy group, 2- (2,2-dichlorocyclopropyl) ethoxy group, (3-chlorocyclopentyl) methoxy group, (3-methoxycyclopentyl) methoxy group, (4-chlorocyclopentyl) methoxy group, (4 -Methoxycyclopentyl) methoxy group, (3-chlorocyclohexyl) methoxy group, (3-methoxycyclohexyl) methoxy group, (4-chlorocyclohexyl) methoxy group, (4-methoxycyclohexyl) methoxy group and the like.
  • Halogen atom represented by R 2 as the C1-C3 alkyl group, C1-C3 alkoxy groups and one or more C6-C10 aryloxy group substituted by a group selected from the group consisting of a trifluoromethyl group, e.g.
  • An anilide compound in which R 2 is substituted at the 4-position of the benzene ring in the formula (I) (the following formula (Ia) [Wherein, A, n, R 1 and R 2 represent the same meaning as described above. ]
  • R 2 in formula (I) is a C1-8 alkyl group optionally substituted by one or more groups selected from the group consisting of a halogen atom and a C1-3 alkoxy group;
  • An anilide compound in which R 2 in formula (I) is a C3-9 alkenyloxy group optionally substituted by one or more groups selected from the group consisting of a halogen atom and a C1-3 alkoxy group;
  • An anilide compound which is an oxy group An anilide compound represented by the formula (I), wherein R 2 is a C6-10 aryloxy group;
  • R 2 is a C6-10 aryloxy group
  • formula (I) anilide wherein R 2 is a (C3-8 cycloalkyl) C1-6 alkoxy group optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-3 alkoxy groups Compound
  • n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is substituted at the 4-position of the benzene ring (following formula (Id) [Wherein, A and n represent the same meaning as described above, and R 2d represents a C1-C8 alkyl group, a C1-C8 alkoxy group, a C3-C9 alkenyloxy group, a C3-C9 alkynyloxy group, a C6-C10 aryloxy group. Or a (C3-C8 cycloalkyl) C1-C6 alkoxy group.
  • the C1-C8 alkyl group, the C1-C8 alkoxy group, the C3-C9 alkenyloxy group, the C3-C9 alkynyloxy group and the (C3-C8 cycloalkyl) C1-C6 alkoxy group represented by R 2d are all May be substituted with one or more groups selected from the group consisting of a halogen atom and a C1-C3 alkoxy group
  • the C6-C10 aryloxy group represented by R 2d is substituted with one or more groups selected from the group consisting of a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group and a trifluoromethyl group. May be.
  • n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is substituted at the 3-position of the benzene ring (the following formula (Id); [Wherein, A and n represent the same meaning as described above, and R 2e represents a C1-C8 alkyl group, a C1-C8 alkoxy group, a C3-C9 alkenyloxy group, a C3-C9 alkynyloxy group, a C6-C10 aryloxy group. Or a (C3-C8 cycloalkyl) C1-C6 alkoxy group.
  • the C1-C8 alkyl group, C1-C8 alkoxy group, C3-C9 alkenyloxy group, C3-C9 alkynyloxy group and (C3-C8 cycloalkyl) C1-C6 alkoxy group represented by R 2e are all May be substituted with one or more groups selected from the group consisting of a halogen atom and a C1-C3 alkoxy group,
  • the C6-C10 aryloxy group represented by R 2e is substituted with one or more groups selected from the group consisting of a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group and a trifluoromethyl group. May be.
  • A is a 6-quinolyl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is substituted at the 4-position of the benzene ring ;
  • A is a 6-quinolyl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is substituted at the 3-position of the benzene ring ;
  • A is a benzothiazol-6-yl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is substituted at the 4-position of the benzene ring
  • A is a benzothiazol-6-yl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is
  • n 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a group consisting of a halogen atom substituted at the 4-position of the benzene ring and a C1-3 alkoxy group
  • n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C1-8 alkyl group substituted at the 4-position of the benzene ring;
  • n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a group consisting of a halogen atom substituted at the 4-position of the benzene ring and a C1-3 alkoxy group
  • n 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, R 2 is a group consisting of a halogen atom substituted at the 3-position of the benzene ring and a C1-3 alkoxy group
  • n 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, R 2 is a group consisting of a halogen atom substituted at the 3-position of the benzene ring and a C1-3 alkoxy group
  • An anilide compound which is n 1, R 1 is a fluorine atom
  • n 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, R 2 is a group consisting of a halogen atom substituted at the 3-position of the benzene ring and a C1-3 alkoxy group
  • An anilide compound which is a C3-9 alkynyloxy group optionally substituted with one or more groups selected from:
  • n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, R 2 is a halogen atom substituted at the 3-position of the benzene ring, a C1-3 alkyl group, C1- An anilide
  • the compound of the present invention can be produced, for example, by the following (Production Method 1) to (Production Method 3).
  • the compound of the present invention can be produced by reacting in the presence of compound (II), compound (III) and a condensing agent.
  • a condensing agent e.g., a benzyl ether
  • THF tetrahydrofuran
  • MTBE ethylene glycol dimethyl ether
  • MTBE tert-butyl methyl ether
  • fats such as hexane, heptane, and octane.
  • Aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as chlorobenzene, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, N, N-dimethylformamide (hereinafter, Acid amides such as DMF), sulfoxides such as dimethyl sulfoxide (hereinafter referred to as DMSO), and mixtures thereof.
  • Aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as chlorobenzene, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, N, N-dimethylformamide (hereinafter, Acid amides such as DMF), sulfoxides such as dimethyl sulfoxide (hereinafter referred to as DMSO), and mixtures thereof.
  • Examples of the condensing agent used in the reaction include 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (hereinafter referred to as WSC) and carbodiimides such as 1,3-dicyclohexylcarbodiimide, (benzotriazole- 1-yloxy) tris (dimethylamino) phosphonium hexafluorophosphate (hereinafter referred to as BOP reagent) and the like.
  • WSC 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride
  • BOP reagent 1,3-dicyclohexylcarbodiimide, (benzotriazole- 1-yloxy) tris (dimethylamino) phosphonium hexafluorophosphate
  • the reaction temperature of the reaction is usually in the range of 0 to 140 ° C.
  • the reaction time is usually in the range of 1 to 24 hours.
  • the compound of the present invention can be isolated by performing post-treatment operations such as filtration of the reaction mixture, extraction of the filtrate with an organic solvent, and drying and concentration of the organic layer.
  • the isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.
  • the compound of the present invention can be produced by reacting compound (II) with compound (IV) or a salt thereof (for example, hydrochloride) in the presence of a base.
  • a base for example, a base
  • A, n, R 1 and R 2 represent the same meaning as described above.
  • the reaction is usually performed in the presence of a solvent.
  • the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, and chlorobenzene.
  • Examples thereof include halogenated hydrocarbons, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, acid amides such as DMF, sulfoxides such as DMSO, and mixtures thereof.
  • Examples of the base used in the reaction include alkali metal carbonates such as sodium carbonate and potassium carbonate, tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. Can be mentioned.
  • compound (IV) is usually used in a proportion of 1 to 3 mol, and base is usually used in a proportion of 1 to 10 mol.
  • the reaction temperature is usually in the range of ⁇ 20 to 100 ° C.
  • the reaction time is usually in the range of 0.1 to 24 hours.
  • the compound of the present invention can be isolated by performing post-treatment operations such as extraction of the reaction mixture with an organic solvent, and drying and concentration of the organic layer. The isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.
  • compound (VII) can be produced by reacting compound (V) with compound (VI) in the presence of a base.
  • a and R 1 represent the same meaning as described above, and L represents a chlorine atom, a bromine atom, an iodine atom, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, or a p-toluenesulfonyloxy group.
  • R 2-1 represents a C1-C8 alkyl group, a C3-C9 alkenyl group, a C3-C9 alkynyl group or a (C3-C8 cycloalkyl) C1-C6 alkyl group substituted at the 3-position or 4-position of the benzene ring.
  • C1-C8 alkyl group represented by the R 2-1 C3-C9 alkenyl group, C3-C9 alkynyl and (C3-C8 cycloalkyl) C1-C6 alkyl group, a halogen atom and C1-C3 alkoxy May be substituted with one or more groups selected from the group consisting of groups
  • the C6-C10 aryl group represented by R 2-1 is substituted with one or more groups selected from the group consisting of a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group and a trifluoromethyl group. May be.
  • the reaction is usually performed in the presence of a solvent.
  • solvent used in the reaction examples include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as chlorobenzene, nitriles such as acetonitrile, DMF, and the like. Acid amides, sulfoxides such as DMSO, ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, water, and mixtures thereof.
  • ethers such as THF, ethylene glycol dimethyl ether, and MTBE
  • aromatic hydrocarbons such as toluene and xylene
  • halogenated hydrocarbons such as chlorobenzene
  • nitriles such as acetonitrile
  • DMF and the like.
  • Examples of the base used in the reaction include alkali metal carbonates such as sodium carbonate, potassium carbonate and cesium carbonate, alkali metal hydroxides such as sodium hydroxide, alkali metal hydrides such as sodium hydride, and the like. .
  • the compound (VI) is usually used in a proportion of 1 to 10 moles, and the base is usually used in a proportion of 1 to 5 moles.
  • the reaction temperature is usually in the range of ⁇ 20 to 100 ° C.
  • the reaction time is usually in the range of 0.1 to 24 hours. After completion of the reaction, when water is added to the reaction mixture and a solid is precipitated, the compound (VII) can be isolated by collecting the solid by filtration.
  • the control agent of the present invention is prepared by mixing the compound of the present invention with a solid carrier, liquid carrier, gas carrier, surfactant, etc. It is formulated into an agent, granular wettable powder, flowable agent, granule, dry flowable agent, emulsion, aqueous liquid agent, oil agent, smoke agent, aerosol agent, microcapsule agent and the like. These preparations contain the compound of the present invention in a weight ratio of usually 0.1 to 99%, preferably 0.2 to 90%.
  • the solid carrier examples include clays (for example, kaolin, diatomaceous earth, synthetic hydrous silicon oxide, fusami clay, bentonite, acidic clay), talc, and other inorganic minerals (for example, sericite, quartz powder, sulfur powder, activated carbon
  • the liquid carrier examples include water, alcohols (for example, methanol, ethanol), ketones (for example, acetone, methyl ethyl ketone), aromatic carbonization, and the like.
  • Hydrogen eg, benzene, toluene, xylene, ethylbenzene, methylnaphthalene
  • aliphatic hydrocarbons eg, n-hexane, cyclohexanone, kerosene
  • esters eg, ethyl acetate, butyl acetate
  • nitriles eg, , Acetonitrile, isobutylnitrile
  • ethers eg If, dioxane, diisopropyl ether
  • acid amides e.g., DMF, dimethylacetamide
  • halogenated hydrocarbons e.g., dichloroethane, trichlorethylene, and carbon tetrachloride
  • surfactant examples include alkyl sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl aryl ethers and polyoxyethylene compounds thereof, polyoxyethylene glycol ethers, polyhydric alcohol esters, sugar alcohol derivatives. Etc.
  • formulation adjuvants include, for example, fixing agents and dispersants, specifically casein, gelatin, polysaccharides (eg starch, arabic gum, cellulose derivatives, alginic acid), lignin derivatives, bentonite, saccharides, synthetic water-soluble high Molecules (eg, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acids), PAP (isopropyl acid phosphate), BHT (2,6-di-tert-butyl-4-methylphenol), BHA (2-tert-butyl-4 -Mixylphenol and 3-tert-butyl-4-methoxyphenol), vegetable oils, mineral oils, fatty acids or esters thereof.
  • fixing agents and dispersants specifically casein, gelatin, polysaccharides (eg starch, arabic gum, cellulose derivatives, alginic acid), lignin derivatives, bentonite, saccharides, synthetic water-soluble high Molecules (eg, poly
  • the method of applying the control agent of the present invention is not particularly limited as long as the control agent of the present invention can be applied substantially. And the like, and the treatment of seeds such as seed disinfection.
  • the present control agent may be used simultaneously with or without mixing with other fungicides, insecticides, acaricides, nematicides, herbicides, plant growth regulators, fertilizers or soil conditioners. You can also.
  • Such other fungicides include, for example, propiconazole, prothioconazole, triazimenol, prochloraz, penconazole, tebuconazole, flusilazole, diniconazole, bromconazole, epoxiconazole, difenoconazole, cyproconazole, metconazole, triflumi Azole fungicides such as sol, tetraconazole, microbutanyl, fenbuconazole, hexaconazole, fluquinconazole, triticonazole, viteltanol, imazalil, flutriahol, cimeconazole, ipconazole; fenpropimorph, tridemorph,
  • organophosphorus compounds such as acephate, aluminum phosphide, butathiofos, cadusafos, chlorethoxyfos, chlorfenvinphos.
  • Ch1orfenvinphos chlorpyrifos
  • chlorpyrifos chlorpyrifos-methyl, cyanophos (CYAP), diazinon (diazinon), DCIP (dichlorodiisopropyl ether), dichlorfenthion (ECP), dichlorvos (DDVP), dimethophos (Dimethoate), dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, etrimfos, fenthion (MPP), fenitrothion (MEP), phosti Zeth (fosthiazate), formothion, hydrogen phosphide, isofenphos, isoxathion, malathion, mesulfenvinphos.
  • acaricides include, for example, acequinocyl, amitraz, benzoximate, bifenaate, phenisobromolate, quinomethionat , Chlorobenzilate, CPCBS (chlorfenson), clofentezine, cyflumetofen, kelofol, etoxazole, fenbutatin oxide, fenothiocarb, fenpyroxycarb (Fenpyroximate), fluacrypyrim, fluproxyfen, hexythiazox, propargite (BPPS), polynactins, polynactins, pyridaben, Pyrimidifen, tebufenpyrad, tetradifon, spirodiclofen, spiromesifen, spirotetramat, amidoflumet, cyenopyrafen, etc.
  • CPCBS chlorfenson
  • clofentezine
  • nematicides include, for example, DCIP, fosthiazate, levamisol hydrochloride, methamiisothiocyanate, morantel tartarate, imicyafos Etc.
  • the application amount of the present control agent varies depending on weather conditions, formulation form, application time, application method, application location, target disease, target crop, etc., but per 10 ares in terms of the amount of the present compound in the present control agent, Usually, it is 1 to 500 g, preferably 2 to 200 g.
  • Emulsions, wettable powders, suspensions and the like are usually diluted with water and applied.
  • the concentration of the compound of the present invention after dilution is usually 0.0005 to 2% by weight, preferably 0.005 to 1.
  • the powder, granules and the like are usually applied as they are without dilution.
  • the amount of the compound of the present invention in the control agent of the present invention is usually 0.001 to 100 g, preferably 0.01 to 50 g per 1 kg seed.
  • the present control agent can be used as a plant disease control agent in farmland such as fields, paddy fields, lawns, orchards.
  • the control agent of the present invention can control diseases of the farmland in the farmland where the following “crop” and the like are cultivated.
  • Agricultural crops corn, rice, wheat, barley, rye, oats, sorghum, cotton, soybeans, peanuts, buckwheat, sugar beet, rapeseed, sunflower, sugarcane, tobacco, vegetables, solanaceous vegetables (eggplants, tomatoes, peppers, peppers, potatoes) Cucumber, pumpkin, zucchini, watermelon, melon, etc., cruciferous vegetables (radish, turnip, horseradish, kohlrabi, cabbage, cabbage, mustard, broccoli, cauliflower, etc.), asteraceae (burdock, Shungiku, artichokes, lettuce, etc.), liliaceae vegetables (leek, onion, garlic, asparagus), celeryaceae vegetables (carrot, parsley, celery, red pepper, etc.), red crustacean vegetables (spinach, chard, etc.) (Perilla, mint, basil ), Strawberry, sweet potato, yam, taro, etc., Bridegroom, Foliage plant, Fruit trees;
  • Trees other than fruit trees Cha, mulberry, flowering trees, street trees (ash, birch, dogwood, eucalyptus, ginkgo, lilac, maple, oak, poplar, redwood, fu, sycamore, zelkova, black bean, peach tree, Tsuga, rat, pine, Spruce, yew) etc.
  • HPPD inhibitors such as isoxaflutole, ALS inhibitors such as imazetapyr and thifensulfuron methyl, EPSP synthase inhibitors, glutamine synthase inhibitors, herbicides such as bromoxynil, This includes crops granted by classical breeding methods or genetic engineering techniques.
  • imidazolinone herbicide-resistant Clearfield canola
  • imazetapil sulfonylurea-based ALS-inhibiting herbicide resistance
  • STS soybeans examples of “crop” to which tolerance has been imparted by genetic engineering techniques include glyphosate and glufosinate-resistant corn varieties that have already been sold under trade names such as RoundupReady (registered trademark) and LibertyLink (registered trademark). Yes.
  • crop includes, for example, crops that can synthesize selective toxins known in the genus Bacillus using genetic recombination techniques.
  • Toxins expressed in such genetically modified plants include insecticidal proteins from Bacillus cereus and Bacillus popirie; Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C from Bacillus thuringiensis Insecticidal proteins such as ⁇ -endotoxin, VIP1, VIP2, VIP3 or VIP3A; nematode-derived insecticidal proteins; toxins produced by animals such as scorpion toxins, spider toxins, bee toxins or insect-specific neurotoxins; filamentous fungal toxins; plants Lectin; agglutinin; protease inhibitors such as trypsin inhibitor, serine protease inhibitor, patatin, cystatin, papain inhibitor; ribosome inactivating protein (RIP)
  • toxins expressed in such genetically modified crops include Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, ⁇ -endotoxin proteins such as Cry3Bb1 or Cry9C, and insecticidal protein hybrids such as VIP1, VIP2, VIP3 or VIP3A Toxins, partially defective toxins, modified toxins are also included. Hybrid toxins are produced by new combinations of different domains of these proteins using recombinant techniques. As a toxin lacking a part, Cry1Ab lacking a part of the amino acid sequence is known. In the modified toxin, one or more amino acids of the natural toxin are substituted.
  • Examples of these toxins and recombinant plants capable of synthesizing these toxins are EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878. , WO 03/052073 and the like.
  • the toxins contained in these recombinant plants particularly confer resistance to Coleoptera pests, Diptera pests, and Lepidoptera pests.
  • transgenic plants that contain one or more insecticidal pest resistance genes and express one or more toxins are already known, and some are commercially available.
  • these transgenic plants include YieldGard® (a corn variety expressing Cry1Ab toxin), YieldGardGRootworm® (a corn variety expressing Cry3Bb1 toxin), YieldGard Plus® (Cry1Ab and Cry3Bb1) Corn varieties that express toxins), Herculex I® (corn varieties that express phosphinotricin N-assyltransferase (PAT) to confer resistance to Cry1Fa2 toxin and glufosinate), NuCOTN33B (Cry1Ac toxin) Cotton varieties expressing), Bollgard I (registered trademark) (cotton varieties expressing Cry1Ac toxin), Bollgard II (registered trademark) (cotton varieties expressing Cry1Ac and Cry2Ab toxin), VIPCOT (registered trademark) (VIP tox
  • the above “crop” includes those given the ability to produce an anti-pathogenic substance having a selective action using genetic recombination technology.
  • PR proteins and the like are known as examples of anti-pathogenic substances (PRPs, EP-A-0 392 225).
  • anti-pathogenic substances and genetically modified plants that produce them are described in EP-A-0 392 225, WO 95/33818, EP-A-0 353 191 and the like.
  • anti-pathogenic substances expressed in such genetically modified plants include, for example, sodium channel inhibitors, calcium channel inhibitors (KP1, KP4, KP6 toxins produced by viruses, etc.) and the like.
  • Ion channel inhibitors include stilbene synthase; bibenzyl synthase; chitinase; glucanase; PR protein; peptide antibiotics, heterocyclic antibiotics, protein factors involved in plant disease resistance 03/000906)) and other anti-pathogenic substances produced by microorganisms.
  • this invention control method is performed by using this invention control agent by the method of applying this invention control agent mentioned above.
  • Rice blast (Magnaporthe grisea), sesame leaf blight (Cochliobolus miyabeanus), blight (Rhizoctonia solani), idiot seedling (Gibberella fujikuroi), yellow dwarf disease (Sclerophthora macrospora); wheat powdery mildew (Sclerophthora macrospora) Erysiphe graminis), red mold disease (Fusarium graminearum, F. avenacerum, F. culmorum, Microdochium nivale), rust disease (Puccinia striiformis, P. graminis, P. recondita, P.
  • apple monilia disease Monilia disease
  • rot Valsa ceratosperma
  • powdery mildew Podosphaera leucotricha
  • spotted leaf disease Alternaria alternata apple pathotype
  • black star Disease Venturia inaequalis
  • anthracnose Glomerella cingulata
  • pear black spot disease Venturia nashicola, V.
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 54 mg of 2′-fluoro-3 ′-(4-pentynyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 39). It was.
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 189 mg of 2′-fluoro-3′-pentyloxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 45).
  • Production Example 46 0.30 g of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.19 g of 1-bromohexane and 0.45 g of cesium carbonate were added to 2 ml of DMF, and the mixture was stirred at room temperature for 20 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 107 mg of 2′-fluoro-3′-hexyloxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 46).
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 215 mg of 2′-fluoro-3 ′-(4-pentenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 47). .
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 252 mg of 2′-fluoro-3 ′-(5-hexenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 48). .
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 205 mg of 2′-fluoro-3 ′-(5-hexynyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 49).
  • Production Example 50 A mixture of 0.16 g of 2-fluoro-3-methoxyaniline, 0.20 g of [1,5] naphthyridine-2-carboxylic acid, 0.29 g of WSC and 3 ml of pyridine was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, and dried under reduced pressure to give 2'-fluoro-3'-methoxy- [1,5 ] -Naphthyridine-2-carboxylic acid anilide (hereinafter referred to as the present compound 50) 0.27 g was obtained.
  • the present compound 50 2'-fluoro-3'-methoxy- [1,5 ] -Naphthyridine-2-carboxylic acid anilide
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 155 mg of 4′-butyl- [1,5] -naphthyridine-2-carboxylic acid anilide (hereinafter referred to as the present compound 55).
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 214 mg of 3′-methyl- [1,5] -naphthyridine-2-carboxylic acid anilide (hereinafter referred to as the present compound 56).
  • Production Example 58 286 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 116 mg of 4-chloro-2-methyl-2-butene and 396 mg of cesium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 6 hours and 30 minutes. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 298 mg of 2′-fluoro-3 ′-(2-pentynyl) oxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 62). .
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 348 mg of 2′-fluoro-3′-octyloxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 66).
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 285 mg of 2′-fluoro-3′-ethoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 67).
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 273 mg of 2′-fluoro-3 ′-(1-methylethoxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 69). .
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 128 mg of 2′-fluoro-3 ′-(3-butenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 71).
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 388 mg of 2′-fluoro-3 ′-(6-heptenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 73). .
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 350 mg of 2′-fluoro-3 ′-(4-methoxybutoxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 74). .
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 312 mg of 2′-fluoro-3 ′-(2-pentenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 75). .
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 343 mg of 2′-fluoro-3 ′-(3-methylbutoxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 76). .
  • the obtained residue was subjected to silica gel column chromatography, so as to obtain 320 mg of 2′-fluoro-3 ′-(2-butenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 77).
  • Reference production example 1 0.95 g of sodium hydroxide was dissolved in 17 ml of water, and 0.33 ml of bromine and 1.0 g of 2-fluoro-3-methoxybenzamide were sequentially mixed at ⁇ 10 ° C. The mixture was stirred at 0 ° C. or lower for 30 minutes and then at 70 ° C. for 1 hour. Water was added to the reaction mixture allowed to cool to around room temperature, and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain 0.29 g of 2-fluoro-3-methoxyaniline.
  • Reference production example 2 1.0 g of hydrochloride of quinoline-6-carboxylic acid chloride and 2.0 g of 3-hydroxyaniline were added to 20 ml of THF, and the mixture was heated to reflux for 4 hours. The reaction mixture was allowed to cool to near room temperature and concentrated under reduced pressure. A saturated aqueous sodium hydrogen carbonate solution was added to the resulting residue, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.60 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide.
  • Reference production example 3 A mixture of 15 g of 3-nitrophenol, 19 g of chloro (1,1-dimethylethyl) dimethylsilane, 11 g of imidazole and 200 ml of DMF was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was extracted twice with hexane. The organic layer was washed successively with 1% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to (1,1-dimethylethyl) dimethylsilyl- (3-nitrophenyl) ether. 30 g was obtained.
  • Reference production example 4 A mixture of 30 g of (1,1-dimethylethyl) dimethylsilyl- (3-nitrophenyl) ether, 0.90 g of 10% palladium on carbon and 150 ml of ethanol was stirred under a hydrogen stream until there was no absorption of hydrogen gas. The reaction mixture was filtered through Celite (registered trademark), and the filtrate was concentrated under reduced pressure to obtain 24 g of 3-[(1,1-dimethylethyl) dimethylsilyloxy] aniline.
  • Reference production example 5 A mixture of 20 g of 3-[(1,1-dimethylethyl) dimethylsilyloxy] aniline, 16 g of quinoline-6-carboxylic acid, 48 g of BOP reagent, 25 ml of triethylamine and 500 ml of DMF was stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure.
  • Reference production example 6 A mixture of 35 g of 3 ′-[(1,1-dimethylethyl) dimethylsilyloxy] -quinoline-6-carboxylic acid anilide, 12 g of lithium hydroxide monohydrate and 150 ml of DMF was stirred at room temperature for 10 hours. Water was added to the reaction mixture and extracted with MTBE. 5% hydrochloric acid was added to the aqueous layer to adjust the pH of the aqueous layer to 7 or less, and the precipitated solid was collected by filtration. The obtained solid was washed with water and then dried under reduced pressure to obtain 28 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide. 3'-hydroxy-quinoline-6-carboxylic acid anilide
  • Reference production example 7 To 10.0 g of 2-fluoro-3-methoxyaniline was mixed 6.6 g of 48% hydrobromic acid at around 10 ° C., and the mixture was heated at 100 ° C. for 20 hours. The reaction mixture was allowed to cool to near room temperature, filtered, 10 ml of 48% hydrobromic acid was added to the obtained crystals, and the mixture was heated at 100 ° C. for 20 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture allowed to cool to about room temperature, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure.
  • Reference production example 9 A reaction in which a mixture of 22 g of 2-fluorophenol, 2.8 g of copper (I) bromide, 23 g of potassium (1,1-dimethylethoxide) and 125 g of bromobenzene was heated and stirred at 150 ° C., and a Dean-Stark separator was connected. The mixture was heated and stirred at 150 ° C. in the container, and 1,1-dimethylethanol was removed from the reaction container by the Dean-Stark separator. The reaction mixture was then heated to reflux for 2 hours. The reaction mixture was allowed to cool to near room temperature, concentrated under reduced pressure, ethyl acetate was added to the residue, and the mixture was filtered through Celite (registered trademark).
  • Reference production example 10 14 g of 2-fluoro-diphenyl ether, 17 ml of N, N, N ′, N ′′, N ′′ -pentamethyldiethylenetriamine and 200 ml of THF were mixed, and 48.5 ml of hexane solution of 1.6 mol / liter of n-butyllithium at ⁇ 70 ° C. Were mixed and stirred at ⁇ 70 ° C. for 2 hours. After mixing dry ice with the reaction mixture, the temperature was gradually raised to room temperature. After concentration under reduced pressure, 5% hydrochloric acid was added to the reaction mixture at 0 ° C., and the mixture was extracted with ethyl acetate.
  • Reference production example 11 A mixture of 10 g of 2-fluoro-3-phenoxybenzenecarboxylic acid, 3.1 ml of thionyl chloride, 1 drop of DMF and 30 ml of toluene was stirred at 80 ° C. for 1 hour and then at 110 ° C. for 2 hours. The reaction mixture was allowed to cool to near room temperature and concentrated under reduced pressure to obtain 11 g of 2-fluoro-3-phenoxybenzenecarboxylic acid chloride.
  • Reference production example 13 2.71 g of sodium hydroxide was dissolved in 45 ml of water, and 1.2 ml of bromine and 4.48 g of 2-fluoro-3-phenoxybenzamide were sequentially mixed at ⁇ 10 ° C. The mixture was stirred at 0 ° C. for 30 minutes and then at 70 ° C. for 6 hours. Ice water was added to the reaction mixture which was allowed to cool to around room temperature, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with a saturated aqueous sodium hydrogen carbonate solution and water, dried over magnesium sulfate, and concentrated under reduced pressure.
  • a part represents a weight part.
  • Formulation Example 1 A wettable powder is obtained by thoroughly pulverizing and mixing 50 parts of any one of the present compounds 1 to 77, 3 parts of calcium lignin sulfonate, 2 parts of magnesium lauryl sulfate and 45 parts of synthetic hydrous hydroxide.
  • Formulation Example 2 20 parts of any one of compounds 1 to 77 of the present invention and 1.5 parts of sorbitan trioleate are mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol, and wet pulverization is used. After finely pulverizing, 40 parts of an aqueous solution containing 0.05 part of xanthan gum and 0.1 part of aluminum magnesium silicate is added thereto, and further 10 parts of propylene glycol is added and mixed by stirring to obtain a flowable preparation. obtain.
  • Formulation Example 3 A powder is obtained by thoroughly pulverizing and mixing 2 parts of the present compound 1 to the present compound 77, 88 parts of kaolin clay and 10 parts of talc.
  • Formulation Example 4 An emulsion is obtained by thoroughly mixing 5 parts of any one of the present compounds 1 to 77, 14 parts of polyoxyethylene styrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 75 parts of xylene.
  • Formulation Example 5 After thoroughly mixing 2 parts of any one of the present compounds 1 to 77, 1 part of synthetic hydrous silicon oxide, 2 parts of calcium lignin sulfonate, 30 parts of bentonite and 65 parts of kaolin clay, water is added. Granules are obtained by kneading well and granulating and drying.
  • Formulation Example 6 By mixing 10 parts of any one of compounds 1 to 77 of the present invention, 35 parts of white carbon containing 50 parts of polyoxyethylene alkyl ether sulfate ammonium salt, and 55 parts of water, and finely pulverizing them by a wet pulverization method. Get a flowable formulation.
  • Formulation Example 7 40 parts of any one of the present compounds 1 to 77, 5 parts of propylene glycol (manufactured by Nacalai Tesque), 5 parts of Soprophor FLK (manufactured by Rhodia Nikka), 0.2 part of anti-form C emulsion (Dow Corning), 0.3 parts of Proxel GXL (manufactured by Arch Chemical Co., Ltd.) and 49.5 parts of ion-exchanged water are mixed to prepare a base slurry.
  • Formulation Example 8 50 parts of any one of compounds 1 to 77 of the present invention, 38.5 parts of NN kaolin clay (manufactured by Takehara Chemical Industries), 10 parts of Morwet D425, 1.5 parts of Morwer EFW (Akzo Nobel) To make an AI premix.
  • the premix is pulverized with a jet mill to obtain a powder.
  • test examples show that the compounds of the present invention are useful for controlling plant diseases.
  • the control effect is obtained by visually observing the area of the lesion on the test plant at the time of the survey, and comparing the area of the lesion on the plant treated with the compound of the present invention and the area of the lesion on the untreated plant. evaluated.
  • comparative compound (A) a compound represented by the following formula (A) described in Example Z-2 of WO 2005/033079 pamphlet
  • comparative compound (B) Compound represented by the following formula (B)
  • Test Example 1 A plastic pot was filled with sand loam, seeded with rice (variety: Nipponbare), and grown in a greenhouse for 20 days. Thereafter, each of the present compounds 1 to 77, the comparative compound (A) and the comparative compound (B) was made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm). The foliage was sprayed so as to adhere well to the surface. After spraying, the plants were air-dried and placed for 6 days in contact with rice seedlings (variety: Nihonbare) afflicted with rice blast fungus (Magnaporthe grisea) at 24 ° C in the daytime and 20 ° C in the nighttime at high humidity. investigated. As a result, the lesion area in the plant which processed this invention compound 22, 24, 30, 31, 50, 59, 61, 64, 77 was 30% or less of the lesion area in an untreated plant.
  • Test Example 2 A plastic pot was filled with sandy loam, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days.
  • Each of the compounds 1 to 77 of the present invention, the comparative compound (A) and the comparative compound (B) was made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm), which was sufficient for the cucumber leaf surface.
  • the foliage was sprayed to adhere. After spraying, the plants were air-dried, and a spore-containing PDA medium of Botrytis cinerea was placed on the cucumber leaf surface. After inoculation, the lesion area was examined after 5 days in a humid environment at 12 ° C.
  • the lesion area in the plant treated with the compound 1, 3, 9, 24, 26, 47, 51, 60, 61, 62, 64, 65, 67, 74, 75, 77 of the present invention was untreated. It was 30% or less of the lesion area in the plant.
  • the lesion area on the plants on which the comparative compound (A) and the comparative compound (B) were tested was 76 to 100% of the lesion area in the untreated group.
  • Test Example 3 A plastic pot was stuffed with sand loam, seeded with wheat (variety: Shirogane), and grown in a greenhouse for 9 days.
  • Each of the compounds 19 to 77 of the present invention was made into a flowable formulation according to Formulation Example 6, diluted with water to a predetermined concentration (500 ppm), and sprayed with foliage so that it was sufficiently attached to the leaf surface of the wheat.
  • the plants were air-dried and cultivated under illumination at 18 ° C. for 5 days, and then inoculated with spores of wheat red rust fungus (Puccinia recondita). After inoculation at 23 ° C. for 1 day under dark and humid conditions, the plant was cultivated under illumination at 18 ° C. for 10 days, and the lesion area was examined. As a result, the lesion area in the plant treated with the present compounds 20, 55 was 30% or less of the lesion area in the untreated plant.
  • Test Example 4 A plastic pot was filled with sandy loam, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days.
  • Each of the compounds 1 to 77 of the present invention, the comparative compound (A) and the comparative compound (B) was made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm), which was sufficient for the cucumber leaf surface.
  • the foliage was sprayed to adhere. After spraying, the plant was air-dried, and a mycelia-containing PDA medium of Sclerotinia sclerotiorum was placed on the cucumber leaf surface. After the inoculation, the lesion area was examined after being placed at 18 ° C.
  • the lesion area in the plant treated with the present compounds 1-7, 9-13, 15-24, 26-54, 56-77 and the comparative compound (A) is the lesion area in the untreated plant. It was 30% or less.
  • Test Example 5 A plastic pot was filled with sandy loam, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days.
  • Each of the compounds 1 to 77 of the present invention, the comparative compound (A) and the comparative compound (B) was made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm), which was sufficient for the cucumber leaf surface.
  • the foliage was sprayed to adhere. After spraying, the plants were air-dried and spray-inoculated with an aqueous suspension of Sphaerotheca furiginea spores.
  • the lesion area in the plant treated with the compounds 24 and 60 of the present invention was 30% or less of the lesion area in the untreated plant.
  • Test Example 6 A plastic pot was filled with sandy loam, wheat (cultivar: Apogee) was sown and grown in a greenhouse for 10 days.
  • Each of the compounds 22 to 77 of the present invention was made into a flowable formulation according to Formulation Example 6, diluted with water to a predetermined concentration (500 ppm), and sprayed with foliage so as to adhere well to the leaf surface of the wheat. After spraying, the plants were air-dried, and after 2 days, sprayed with a water suspension of Septoria tritici spores. After the inoculation, the area was first placed under high humidity at 18 ° C. for 3 days and further under illumination for 14 to 18 days, and then the lesion area was examined. As a result, the lesion area in the plant treated with the present compounds 24, 26, 27, 56, 59, 60, 64, 65 was 30% or less of the lesion area in the untreated plant.
  • Test Example 7 A plastic pot was filled with sand loam, sown with grapes (variety: seedlings of berry A), and grown in a greenhouse for 40 days. The above-mentioned pot was spray-inoculated with a water suspension of grape mildew zoosporangium, placed at 23 ° C. under high humidity for 1 day, and then air-dried to obtain a seedling infected with grape mildew (Plasmopara viticola).
  • Each of the compounds 1 to 70 of the present invention, the comparative compound (A) and the comparative compound (B) is made into a flowable preparation according to Preparation Example 6, and then diluted with water to a predetermined concentration (500 ppm).
  • the foliage was sprayed so as to adhere well. After spraying, the plants were air-dried, placed in a 23 ° C. greenhouse for 5 days, and further placed at 23 ° C. and humid for 1 day, and then the lesion area was examined. As a result, the lesion area in the plant treated with the compound 15 of the present invention was 30% or less of the lesion area in the untreated plant.
  • Test Example 8 A plastic pot is filled with Fusarium oxysporum contaminated soil, seeded with tomato (variety: patio), each of the present compounds 1 to 77 is made into a flowable formulation according to Formulation Example 6, and then diluted with water. 10 mg of compound per soil pot is soil irrigated. After growing in a greenhouse for 1 month, compare with untreated plants. As a result, the plants treated with the compounds 1 to 77 of the present invention have no lesions, and the same good growth as that of plants grown on non-contaminated soil is observed.
  • Test Example 9 A plastic pot is filled with soil contaminated with potato half body wilt (Verticillium albo-atrum, v. Dahliae, v. Nigrescens), potatoes (variety: baron) are planted, and each of the compounds 1 to 77 of the present invention is prepared according to Formulation Example 6. After making the flowable formulation, the mixture is diluted with water and 10 mg of the compound per soil pot is soil irrigated. After growing in a greenhouse for 2 months, compare with untreated plants. As a result, the plants treated with the compounds 1 to 77 of the present invention have no lesions, and the same good growth as that of plants grown on non-contaminated soil is observed.
  • Test Example 10 Each of the compounds 1 to 77 of the present invention is made into a flowable formulation according to Formulation Example 6, and then 200 g of the compound per 100 kg seed is treated with a rice-fouling fungus (Gibberella fujikuroi) contaminated pod. Then, after cultivating for 1 month in a greenhouse, it compares with an untreated plant. As a result, the plants treated with the compounds 1 to 77 of the present invention have good growth equivalent to the plants grown from non-contaminated cocoons.
  • a rice-fouling fungus Gibberella fujikuroi
  • Test Example 11 Each of the compounds 1 to 77 of the present invention is made into a flowable formulation according to Formulation Example 6, and then 200 g of the compound per 100 kg seed is treated with seeds contaminated with Gaeumanomyces graminis. Then, after cultivating for 1 month in a greenhouse, it compares with an untreated plant. As a result, the plants treated with the compounds 1 to 77 of the present invention show good growth equivalent to plants grown from non-contaminated seeds.
  • Test Example 12 Each of the compounds 1 to 77 of the present invention is made into a flowable formulation according to Formulation Example 7, and then 200 g of the compound per 100 kg seed is seed-treated in rice stagnation fungus (Gibberella fujikuroi) contaminated pods. Then, after cultivating for 1 month in a greenhouse, it compares with an untreated plant. As a result, the plants treated with the compounds 1 to 77 of the present invention have good growth equivalent to the plants grown from non-contaminated cocoons.
  • Test Example 13 Each of the compounds 1 to 77 of the present invention is made into a flowable formulation according to Formulation Example 7, and then 200 g of the compound per 100 kg seed is treated with seeds contaminated with Gaeumanomyces graminis. Then, after cultivating for 1 month in a greenhouse, it compares with an untreated plant. As a result, the plants treated with the compounds 1 to 77 of the present invention show good growth equivalent to plants grown from non-contaminated seeds.

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Abstract

Disclosed is an anilide compound represented by formula (I), which has excellent control activity against plant diseases. Consequently, the anilide compound is effective as an active ingredient of a plant disease control agent. [In the formula, A represents a 6-quinolyl group, a benzothiazol-6-yl group or a [1,5]naphthyridin-2-yl group; n represents an integer of 0-4; R1 represents a halogen atom or a C1-C3 alkyl group; and R2 represents a C1-C8 alkyl group substituted at the 3-position or the 4-position of the benzene ring or the like.]

Description

アニリド化合物及びその用途Anilide compounds and uses thereof
　本発明は、アニリド化合物及びその植物病害防除用途に関する。 The present invention relates to an anilide compound and its use for controlling plant diseases.
　植物病害防除剤の有効成分として多くの化合物が開発され、実用に供されている。しかしながら、これらの化合物が必ずしも十分な防除効力を示さない場合もある。 Many compounds have been developed and put into practical use as active ingredients for plant disease control agents. However, there are cases where these compounds do not necessarily show sufficient control efficacy.
　本発明は、植物病害に対して優れた防除効力を有する化合物を提供することを課題とする。 An object of the present invention is to provide a compound having an excellent control effect against plant diseases.
本発明は以下のものである。
［１］　式（Ｉ）
Figure JPOXMLDOC01-appb-C000002
 〔式中、
Ａは、６－キノリル基、ベンゾチアゾール－６－イル基又は［１，５］ナフチリジン－２－イル基を表し、
ｎは、０～４の整数のいずれかを表し、
Ｒ１は、ハロゲン原子又はＣ１－Ｃ３アルキル基を表し、
Ｒ２は、ベンゼン環の３位又は４位に置換した、Ｃ１－Ｃ８アルキル基、Ｃ１－Ｃ８アルコキシ基、Ｃ３－Ｃ９アルケニルオキシ基、Ｃ３－Ｃ９アルキニルオキシ基、Ｃ６－Ｃ１０アリールオキシ基又は（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルコキシ基を表す。
ここで、該Ｒ２で示されるＣ１－Ｃ８アルキル基、Ｃ１－Ｃ８アルコキシ基、Ｃ３－Ｃ９アルケニルオキシ基、Ｃ３－Ｃ９アルキニルオキシ基及び（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルコキシ基は、ハロゲン原子及びＣ１－Ｃ３アルコキシ基からなる群より選ばれる１以上の基で置換されていてもよく、
また、該Ｒ２で示されるＣ６－Ｃ１０アリールオキシ基は、ハロゲン原子、Ｃ１－Ｃ３アルキル基、Ｃ１－Ｃ３アルコキシ基及びトリフルオロメチル基からなる群より選ばれる１以上の基で置換されていてもよく、
但し、ｎが０であり、Ｒ２がベンゼン環の３位に置換したトリフルオロメチル基である場合、Ａはベンゾチアゾール－６－イル基又は［１，５］ナフチリジン－２－イル基を表し、
ｎが２、３又は４である場合、Ｒ１は互いに同一又は相異なる。〕で示されるアニリド化合物（以下、本発明化合物と記す。）。
［２］　Ａが、６－キノリル基である［１］記載のアニリド化合物。
［３］　Ｒ２の置換位置がベンゼン環の３位である［１］又は［２］記載のアニリド化合物。
［４］　Ａが６－キノリル基であり、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したメトキシ基である［１］記載のアニリド化合物。
［５］　３’－（４－ペンチニルオキシ）－キノリン－６－カルボン酸アニリド。
［６］　３’－ブチルオキシ－キノリン－６－カルボン酸アニリド。
［７］　３’－（２－ペンテニルオキシ）－キノリン－６－カルボン酸アニリド。
［８］　３’－（４－ペンテニルオキシ）－キノリン－６－カルボン酸アニリド。
［９］　２’－フルオロ－３’－（４－ペンチニルオキシ）－キノリン－６－カルボン酸アニリド。
［１０］　２’－フルオロ－３’－（４－ペンテニルオキシ）－キノリン－６－カルボン酸アニリド。
［１１］　２’－フルオロ－３’－（５－ヘキセニルオキシ）－キノリン－６－カルボン酸アニリド。
［１２］　２’－フルオロ－３’－（５－ヘキシニルオキシ）－キノリン－６－カルボン酸アニリド。
［１３］　２’－フルオロ－３’－（２－メチル－プロピルオキシ）－キノリン－６－カルボン酸アニリド。
［１４］　２’－フルオロ－３’－（２－ブチニルオキシ）キノリン－６－カルボン酸アニリド。
［１５］　２’－フルオロ－３’－（３－エトキシプロピルオキシ）キノリン－６－カルボン酸アニリド。
［１６］　２’－フルオロ－３’－（２－プロペニルオキシ）－キノリン－６－カルボン酸アニリド。
［１７］　２’－フルオロ－３’－エトキシ－キノリン－６－カルボン酸アニリド。
［１８］　２’－フルオロ－３’－ブトキシ－キノリン－６－カルボン酸アニリド。
［１９］　［１］から［１８］いずれか１項記載のアニリド化合物を含有する植物病害防除剤（以下、本発明防除剤と記す。）。
［２０］　［１］から［１８］いずれか１項記載のアニリド化合物の有効量を植物又は土壌に施用する工程を有する植物病害の防除方法。
［２１］　植物病害を防除するための［１］から［１８］いずれか１項記載のアニリド化合物の使用。 The present invention is as follows.
[1] Formula (I)
Figure JPOXMLDOC01-appb-C000002
 [Where,
A represents a 6-quinolyl group, a benzothiazol-6-yl group or a [1,5] naphthyridin-2-yl group;
n represents an integer of 0 to 4,
R 1 represents a halogen atom or a C1-C3 alkyl group,
R 2 represents a C1-C8 alkyl group, a C1-C8 alkoxy group, a C3-C9 alkenyloxy group, a C3-C9 alkynyloxy group, a C6-C10 aryloxy group substituted at the 3-position or 4-position of the benzene ring, or ( C3-C8 cycloalkyl) represents a C1-C6 alkoxy group.
Here, the C1-C8 alkyl group, C1-C8 alkoxy group, C3-C9 alkenyloxy group, C3-C9 alkynyloxy group and (C3-C8 cycloalkyl) C1-C6 alkoxy group represented by R 2 are halogenated. May be substituted with one or more groups selected from the group consisting of atoms and C1-C3 alkoxy groups,
The C6-C10 aryloxy group represented by R 2 is substituted with one or more groups selected from the group consisting of a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group and a trifluoromethyl group. Well,
However, when n is 0 and R 2 is a trifluoromethyl group substituted at the 3-position of the benzene ring, A represents a benzothiazol-6-yl group or a [1,5] naphthyridin-2-yl group. ,
When n is 2, 3 or 4, R 1 is the same or different from each other. ] The anilide compound shown below (it is hereafter described as this invention compound).
[2] The anilide compound according to [1], wherein A is a 6-quinolyl group.
[3] The anilide compound according to [1] or [2], wherein R 2 is substituted at the 3-position of the benzene ring.
[4] A is a 6-quinolyl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a methoxy group substituted at the 3-position of the benzene ring [ 1] The anilide compound according to the above.
[5] 3 ′-(4-Pentynyloxy) -quinoline-6-carboxylic acid anilide.
[6] 3′-Butyloxy-quinoline-6-carboxylic acid anilide.
[7] 3 ′-(2-pentenyloxy) -quinoline-6-carboxylic acid anilide.
[8] 3 ′-(4-Pentenyloxy) -quinoline-6-carboxylic acid anilide.
[9] 2′-Fluoro-3 ′-(4-pentynyloxy) -quinoline-6-carboxylic acid anilide.
[10] 2′-Fluoro-3 ′-(4-pentenyloxy) -quinoline-6-carboxylic acid anilide.
[11] 2′-Fluoro-3 ′-(5-hexenyloxy) -quinoline-6-carboxylic acid anilide.
[12] 2′-Fluoro-3 ′-(5-hexynyloxy) -quinoline-6-carboxylic acid anilide.
[13] 2′-Fluoro-3 ′-(2-methyl-propyloxy) -quinoline-6-carboxylic acid anilide.
[14] 2′-Fluoro-3 ′-(2-butynyloxy) quinoline-6-carboxylic acid anilide.
[15] 2′-Fluoro-3 ′-(3-ethoxypropyloxy) quinoline-6-carboxylic acid anilide.
[16] 2′-Fluoro-3 ′-(2-propenyloxy) -quinoline-6-carboxylic acid anilide.
[17] 2′-Fluoro-3′-ethoxy-quinoline-6-carboxylic acid anilide.
[18] 2′-Fluoro-3′-butoxy-quinoline-6-carboxylic acid anilide.
[19] A plant disease control agent comprising the anilide compound according to any one of [1] to [18] (hereinafter referred to as the present invention control agent).
[20] A method for controlling plant diseases comprising a step of applying an effective amount of the anilide compound according to any one of [1] to [18] to a plant or soil.
[21] Use of the anilide compound according to any one of [1] to [18] for controlling plant diseases.
　本発明において、
Ｒ１で示される
ハロゲン原子としては、フッ素原子、塩素原子、臭素原子及びヨウ素原子が挙げられ、
Ｃ１－Ｃ３アルキル基としては、メチル基、エチル基、プロピル基及びイソプロピル基が挙げられ、
Ｒ２で示されるＣ１－Ｃ８アルキル基としては、例えばメチル基、エチル基、プロピル基、ブチル基、イソブチル基、ペンチル基、ヘキシル基、４－メチルペンチル基、３－メチルペンチル基、ヘプチル基及びオクチル基が挙げられる。
Ｒ２で示されるＣ１－Ｃ８アルコキシ基としては、例えばメトキシ基、エトキシ基、１－メチルエトキシ基、プロポキシ基、１－メチルプロポキシ基、２－メチルプロポキシ基、ブトキシ基、１－メチルブトキシ基、２－メチルブトキシ基、３－メチルブトキシ基、２，３－ジメチルブトキシ基、ペンチルオキシ基、１－メチルペンチルオキシ基、２－メチルペンチルオキシ基、３－メチルペンチルオキシ基、４－メチルペンチルオキシ基、ヘキシルオキシ基、ヘプチルオキシ基及びオクチルオキシ基が挙げられる。
Ｒ２で示されるＣ３－Ｃ９アルケニルオキシ基としては、例えば２－プロペニルオキシ基、１－メチル－２－プロぺニルオキシ基、２－メチル－２－プロぺニルオキシ基、２－ブテニルオキシ基、３－メチル－２－ブテニルオキシ基、３－ブテニルオキシ基、３－メチル－３－ブテニルオキシ基、２－ペンテニルオキシ基、３－ペンテニルオキシ基、４－ペンテニルオキシ基、プレニルオキシ基、４－メチル－４－ペンテニルオキシ基、４－メチル－３－ペンテニルオキシ基、２－ヘキセニルオキシ基、３－ヘキセニルオキシ基、４－ヘキセニルオキシ基、５－ヘキセニルオキシ基、２－ヘプテニルオキシ基、３－ヘプテニルオキシ基、４－ヘプテニルオキシ基、５－ヘプテニルオキシ基、６－ヘプテニルオキシ基、２－オクテニルオキシ基、３－オクテニルオキシ基、４－オクテニルオキシ基、５－オクテニルオキシ基、６－オクテニルオキシ基及び７－オクテニルオキシ基が挙げられる。
Ｒ２で示されるＣ３－Ｃ９アルキニルオキシ基としては、例えば２－プロピニルオキシ基、２－ブチニルオキシ基、３－ブチニルオキシ基、２－ペンチニルオキシ基、３－ペンチニルオキシ基、４－ペンチニルオキシ基、２－ヘキシニルオキシ基、３－ヘキシニルオキシ基、４－ヘキシニルオキシ基、５－ヘキシニルオキシ基、２－ヘプチニルオキシ基、３－ヘプチニルオキシ基、４－ヘプチニルオキシ基、５－ヘプチニルオキシ基、６－ヘプチニルオキシ基、２－オクチニルオキシ基、３－オクチニルオキシ基、４－オクチニルオキシ基、５－オクチニルオキシ基、６－オクチニルオキシ基及び７－オクチニルオキシ基が挙げられる。
Ｒ２で示されるＣ６－Ｃ１０アリールオキシ基としては、例えばフェノキシ基及びナフトキシ基が挙げられる。
Ｒ２で示される（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルコキシ基としては、例えばシクロプロピルメトキシ基、シクロプロピルエトキシ基、シクロプロピルプロポキシ基、シクロプロピルブトキシ基、シクロプロピルペンチルオキシ基、シクロプロピルヘキシルオキシ基、シクロブチルメトキシ基、シクロブチルエトキシ基、シクロブチルプロポキシ基、シクロブチルブトキシ基、シクロブチルペンチルオキシ基、シクロペンチルメトキシ基、シクロペンチルエトキシ基、シクロペンチルプロポキシ基、シクロペンチルブトキシ基、シクロヘキシルメトキシ基及びシクロヘキシルエトキシ基が挙げられる。
Ｒ２で示されるＣ１－Ｃ８アルキル基、Ｃ１－Ｃ８アルコキシ基、Ｃ３－Ｃ９アルケニルオキシ基、Ｃ３－Ｃ９アルキニルオキシ基及び（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルコキシ基はハロゲン原子及びＣ１－Ｃ３アルコキシ基からなる群より選ばれる１以上の基で置換されていてもよい。
この場合のハロゲン原子としては、フッ素原子、塩素原子、臭素原子及びヨウ素原子が挙げられ、
この場合のＣ１－Ｃ３アルコキシ基としては、メトキシ基、エトキシ基、プロポキシ基及びイソプロポキシ基が挙げられる。
Ｒ２で示されるＣ６－Ｃ１０アリールオキシ基は、ハロゲン原子、Ｃ１－Ｃ３アルキル基、Ｃ１－Ｃ３アルコキシ基及びトリフルオロメチル基からなる群より選ばれる１以上の基で置換されていてもよい。
この場合のハロゲン原子としては、フッ素原子、塩素原子、臭素原子及びヨウ素原子が挙げられ、
この場合のＣ１－Ｃ３アルキル基としては、メチル基、エチル基、プロピル基及びイソプロピル基が挙げられ、
この場合のＣ１－Ｃ３アルコキシ基としては、メトキシ基、エトキシ基、プロポキシ基及びイソプロポキシ基が挙げられる。 In the present invention,
Examples of the halogen atom represented by R 1 include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.
Examples of the C1-C3 alkyl group include a methyl group, an ethyl group, a propyl group, and an isopropyl group.
The C1-C8 alkyl group represented by R 2, a methyl group, an ethyl group, a propyl group, a butyl group, an isobutyl group, a pentyl group, a hexyl group, 4-methylpentyl group, 3-methylpentyl group, heptyl group and An octyl group is mentioned.
Examples of the C1-C8 alkoxy group represented by R 2 include methoxy group, ethoxy group, 1-methylethoxy group, propoxy group, 1-methylpropoxy group, 2-methylpropoxy group, butoxy group, 1-methylbutoxy group, 2-methylbutoxy group, 3-methylbutoxy group, 2,3-dimethylbutoxy group, pentyloxy group, 1-methylpentyloxy group, 2-methylpentyloxy group, 3-methylpentyloxy group, 4-methylpentyloxy group Group, hexyloxy group, heptyloxy group and octyloxy group.
Examples of the C3-C9 alkenyloxy group represented by R 2 include 2-propenyloxy group, 1-methyl-2-propenyloxy group, 2-methyl-2-propenyloxy group, 2-butenyloxy group, 3- Methyl-2-butenyloxy group, 3-butenyloxy group, 3-methyl-3-butenyloxy group, 2-pentenyloxy group, 3-pentenyloxy group, 4-pentenyloxy group, prenyloxy group, 4-methyl-4-pentenyl Oxy group, 4-methyl-3-pentenyloxy group, 2-hexenyloxy group, 3-hexenyloxy group, 4-hexenyloxy group, 5-hexenyloxy group, 2-heptenyloxy group, 3-heptenyloxy group, 4-heptenyloxy group Group, 5-heptenyloxy group, 6-heptenyloxy group, 2-octenyloxy group , 3-octenyloxy group, 4-octenyloxy group, 5-octenyloxy group, 6-octenyloxy group and 7-octenyloxy group.
Examples of the C3-C9 alkynyloxy group represented by R 2 include 2-propynyloxy group, 2-butynyloxy group, 3-butynyloxy group, 2-pentynyloxy group, 3-pentynyloxy group, 4-pentynyloxy group, and the like. Group, 2-hexynyloxy group, 3-hexynyloxy group, 4-hexynyloxy group, 5-hexynyloxy group, 2-heptynyloxy group, 3-heptynyloxy group, 4-heptynyloxy group, 5-heptynyloxy group, 6-heptynyloxy group, 2-octynyloxy group Group, 3-octynyloxy group, 4-octynyloxy group, 5-octynyloxy group, 6-octynyloxy group and 7-octynyloxy group.
Examples of the C6-C10 aryloxy group represented by R 2 include a phenoxy group and a naphthoxy group.
Examples of the (C3-C8 cycloalkyl) C1-C6 alkoxy group represented by R 2 include cyclopropylmethoxy group, cyclopropylethoxy group, cyclopropylpropoxy group, cyclopropylbutoxy group, cyclopropylpentyloxy group, cyclopropylhexyl. Oxy, cyclobutylmethoxy, cyclobutylethoxy, cyclobutylpropoxy, cyclobutylbutoxy, cyclobutylpentyloxy, cyclopentylmethoxy, cyclopentylethoxy, cyclopentylpropoxy, cyclopentylbutoxy, cyclohexylmethoxy and cyclohexyl An ethoxy group is mentioned.
The C1-C8 alkyl group, C1-C8 alkoxy group, C3-C9 alkenyloxy group, C3-C9 alkynyloxy group and (C3-C8 cycloalkyl) C1-C6 alkoxy group represented by R 2 are a halogen atom and C1-C3 It may be substituted with one or more groups selected from the group consisting of alkoxy groups.
Examples of the halogen atom in this case include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
Examples of the C1-C3 alkoxy group in this case include a methoxy group, an ethoxy group, a propoxy group, and an isopropoxy group.
The C6-C10 aryloxy group represented by R 2 may be substituted with one or more groups selected from the group consisting of a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group and a trifluoromethyl group.
Examples of the halogen atom in this case include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
Examples of the C1-C3 alkyl group in this case include a methyl group, an ethyl group, a propyl group, and an isopropyl group.
Examples of the C1-C3 alkoxy group in this case include a methoxy group, an ethoxy group, a propoxy group, and an isopropoxy group.
Ｒ２で示されるハロゲン原子及びＣ１－Ｃ３アルコキシ基からなる群より選ばれる１種以上の基で置換されているＣ１－Ｃ８アルキル基としては、例えばフルオロメチル基、ジフルオロメチル基、トリフルオロメチル基、クロロメチル基、ジクロロメチル基、トリクロロメチル基、ブロモメチル基、１－フルオロエチル基、１－クロロエチル基、１－ブロモエチル基、２－フルオロエチル基、２－クロロエチル基、２－ブロモエチル基、２，２，２－トリフルオロエチル基、ペンタフルオロエチル基、１－トリフルオロメチル－２，２，２－トリフルオロエチル基、３－フルオロプロピル基、３，３，３－トリフルオロプロピル基、２，２，３，３，３－ペンタフルオロプロピル基、３－クロロプロピル基、４－フルオロブチル基、４－クロロブチル基、５－フルオロペンチル基、５－クロロペンチル基、６－フルオロヘキシル基、６－クロロヘキシル基、７－フルオロヘプチル基、７－クロロヘプチル基、８－フルオロオクチル基、８－クロロオクチル基、
メトキシメチル基、エトキシメチル基、プロポキシメチル基、（２－メチルエトキシ）メチル基、ジメトキシメチル基、ジエトキシメチル基、１－メトキシエチル基、２－メトキシエチル基、２，２－ジメトキシエチル基、２－エトキシエチル基、２－プロポキシエチル基、３－メトキシプロピル基、３－エトキシプロピル基、３－プロポキシプロピル基、４－メトキシブチル基、４－エトキシブチル基、４－プロポキシブチル基、５－メトキシペンチル基、５－エトキシペンチル基、５－プロポキシペンチル基、６－メトキシヘキシル基、６－エトキシヘキシル基、６－プロポキシヘキシル基、７－メトキシヘプチル基、７－エトキシヘプチル基、７－プロポキシヘプチル基、８－メトキシオクチル基、８－エトキシオクチル基及び８－プロポキシオクチル基が挙げられる。
Ｒ２で示されるハロゲン原子及びＣ１－Ｃ３アルコキシ基からなる群より選ばれる１種以上の基で置換されているＣ１－Ｃ８アルコキシ基としては、例えばトリフルオロメトキシ基、１－フルオロエトキシ基、２－フルオロエトキシ基、２－クロロエトキシ基、２－ブロモエトキシ基、２，２，２－トリフルオロエトキシ基、ペンタフルオロエトキシ基、１－トリフルオロメチル－２，２，２－トリフルオロエトキシ基、３－フルオロプロポキシ基、３，３，３－トリフルオロプロポキシ基、２，２，３，３，３－ペンタフルオロプロポキシ基、３－クロロプロポキシ基、４－フルオロブトキシ基、４－クロロブトキシ基、５－フルオロペンチルオキシ基、５－クロロペンチルオキシ基、６－フルオロヘキシルオキシ基、６－クロロヘキシルオキシ基、７－フルオロヘプチルオキシ基、７－クロロヘプチルオキシ基、８－フルオロオクチルオキシ基、８－クロロオクチルオキシ基、
メトキシメトキシ基、エトキシメトキシ基、２－メトキシエトキシ基、２，２－ジメトキシエトキシ基、２－エトキシエトキシ基、２－プロポキシエトキシ基、３－メトキシプロポキシ基、３－エトキシプロポキシ基、３－プロポキシプロポキシ基、４－メトキシブトキシ基、４－エトキシブトキシ基、４－プロポキシブトキシ基、５－メトキシペンチルオキシ基、５－エトキシペンチルオキシ基、５－プロポキシペンチルオキシ基、６－メトキシヘキシルオキシ基、６－エトキシヘキシルオキシ基、６－プロポキシヘキシルオキシ基、７－メトキシヘプチルオキシ基、７－エトキシヘプチルオキシ基、７－プロポキシヘプチルオキシ基、８－メトキシオクチルオキシ基、８－エトキシオクチルオキシ基及び８－プロポキシオクチルオキシ基が挙げられる。
Ｒ２で示されるハロゲン原子及びＣ１－Ｃ３アルコキシ基からなる群より選ばれる１種以上の基で置換されているＣ３－Ｃ９アルケニルオキシ基としては、例えば３，３－ジフルオロ－２－プロペニルオキシ基、２－クロロ－２－プロペニルオキシ基、３－クロロ－２－プロペニルオキシ基、３，３－ジクロロ－２－プロペニルオキシ基、２，３，３－トリクロロ－２－プロペニルオキシ基、４－クロロ－２－ブテニルオキシ基、４－ブロモ－２－ブテニルオキシ基、４－メトキシ－２－ブテニルオキシ基、４－エトキシ－２－ブテニルオキシ基、３－クロロ－３－ブテニルオキシ基、５－クロロ－２－ペンテニルオキシ基、５－ブロモ－２－ペンテニルオキシ基、５－メトキシ－２－ペンテニルオキシ基、５－クロロ－３－ペンテニルオキシ基、５－ブロモ－３－ペンテニルオキシ基、５－メトキシ－３－ペンテニルオキシ基、６－クロロ－３－ヘキセニルオキシ基、６－ブロモ－３－ヘキセニルオキシ基、６－メトキシ－３－ヘキセニルオキシ基、６－クロロ－４－ヘキセニルオキシ基、６－ブロモ－４－ヘキセニルオキシ基、６－メトキシ－４－ヘキセニルオキシ基、７－クロロ－３－ヘプテニルオキシ基、７－ブロモ－３－ヘプテニルオキシ基、７－メトキシ－３－ヘプテニルオキシ基、７－クロロ－４－ヘプテニルオキシ基、７－ブロモ－４－ヘプテニルオキシ基、７－メトキシ－４－ヘプテニルオキシ基、７－クロロ－５－ヘプテニルオキシ基、７－ブロモ－５－ヘプテニルオキシ基、７－メトキシ－５－ヘプテニルオキシ基、８－クロロ－３－オクテニルオキシ基、８－ブロモ－３－オクテニルオキシ基、８－メトキシ－３－オクテニルオキシ基、８－クロロ－４－オクテニルオキシ基、８－ブロモ－４－オクテニルオキシ基、８－メトキシ－４－オクテニルオキシ基、８－クロロ－５－オクテニルオキシ基、８－ブロモ－５－オクテニルオキシ基及び８－メトキシ－５－オクテニルオキシ基が挙げられる。
Ｒ２で示されるハロゲン原子及びＣ１－Ｃ３アルコキシ基からなる群より選ばれる１種以上の基で置換されているＣ３－Ｃ９アルキニルオキシ基としては、例えば４－クロロ－２－ブチニルオキシ基、４－ブロモ－２－ブチニルオキシ基、４－メトキシ－２－ブチニルオキシ基、５－クロロ－２－ペンチニルオキシ基、５－ブロモ－２－ペンチニルオキシ基、５－メトキシ－２－ペンチニルオキシ基、５－クロロ－３－ペンチニルオキシ基、５－ブロモ－３－ペンチニルオキシ基、５－メトキシ－３－ペンチニルオキシ基、６－クロロ－３－ヘキシニルオキシ基、６－ブロモ－３－ヘキシニルオキシ基、６－メトキシ－３－ヘキシニルオキシ基、６－クロロ－４－ヘキシニルオキシ基、６－ブロモ－４－ヘキシニルオキシ基、６－メトキシ－４－ヘキシニルオキシ基、７－クロロ－３－ヘプチニルオキシ基、７－ブロモ－３－ヘプチニルオキシ基、７－メトキシ－３－ヘプチニルオキシ基、７－クロロ－４－ヘプチニルオキシ基、７－ブロモ－４－ヘプチニルオキシ基、７－メトキシ－４－ヘプチニルオキシ基、７－クロロ－５－ヘプチニルオキシ基、７－ブロモ－５－ヘプチニルオキシ基、７－メトキシ－５－ヘプチニルオキシ基、８－クロロ－３－オクチニルオキシ基、８－ブロモ－３－オクチニルオキシ基、８－メトキシ－３－オクチニルオキシ基、８－クロロ－４－オクチニルオキシ基、８－ブロモ－４－オクチニルオキシ基、８－メトキシ－４－オクチニルオキシ基、８－クロロ－５－オクチニルオキシ基、８－ブロモ－５－オクチニルオキシ基、８－メトキシ－５－オクチニルオキシ基、８－クロロ－６－オクチニルオキシ基、８－ブロモ－６－オクチニルオキシ基及び８－メトキシ－６－オクチニルオキシ基が挙げられる。
Ｒ２で示されるハロゲン原子及びＣ１－Ｃ３アルコキシ基からなる群より選ばれる１種以上の基で置換されている（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルコキシ基としては、例えば（２，２－ジクロロシクロプロピル）メトキシ基、２－（２，２－ジクロロシクロプロピル）エトキシ基、（３－クロロシクロペンチル）メトキシ基、（３－メトキシシクロペンチル）メトキシ基、（４－クロロシクロペンチル）メトキシ基、（４－メトキシシクロペンチル）メトキシ基、（３－クロロシクロヘキシル）メトキシ基、（３－メトキシシクロヘキシル）メトキシ基、（４－クロロシクロヘキシル）メトキシ基及び（４－メトキシシクロヘキシル）メトキシ基等が挙げられる。
Ｒ２で示されるハロゲン原子、Ｃ１－Ｃ３アルキル基、Ｃ１－Ｃ３アルコキシ基及びトリフルオロメチル基からなる群より選ばれる１種以上の基で置換されているＣ６－Ｃ１０アリールオキシ基としては、例えば２－フルオロフェノキシ基、３－フルオロフェノキシ基、４－フルオロフェノキシ基、２，４－ジフルオロフェノキシ基、３，４－ジフルオロフェノキシ基、２－クロロフェノキシ基、３－クロロフェノキシ基、４－クロロフェノキシ基、３，４－ジクロロフェノキシ基、２－メチルフェノキシ基、３－メチルフェノキシ基、４－メチルフェノキシ基、３，５－ジメチルフェノキシ基、４－ブロモフェノキシ基、３－エチルフェノキシ基、４－エチルフェノキシ基、３－プロピルフェノキシ基、４－プロピルフェノキシ基、２－メトキシフェノキシ基、３－メトキシフェノキシ基、４－メトキシフェノキシ基、３，４－ジメトキシフェノキシ基、３－エトキシフェノキシ基、４－エトキシフェノキシ基、３－プロポキシフェノキシ基、４－プロポキシフェノキシ基、２－トリフルオロメチルフェノキシ基、３－トリフルオロメチルフェノキシ基、４－トリフルオロメチルフェノキシ基、２－クロロ－４－トリフルオロメチルフェノキシ基、２－フルオロ－３－メトキシ基及び２－フルオロ－４－メトキシ基が挙げられる。 Examples of the C1-C8 alkyl group substituted with one or more groups selected from the group consisting of a halogen atom represented by R 2 and a C1-C3 alkoxy group include a fluoromethyl group, a difluoromethyl group, and a trifluoromethyl group. Chloromethyl group, dichloromethyl group, trichloromethyl group, bromomethyl group, 1-fluoroethyl group, 1-chloroethyl group, 1-bromoethyl group, 2-fluoroethyl group, 2-chloroethyl group, 2-bromoethyl group, 2, 2,2-trifluoroethyl group, pentafluoroethyl group, 1-trifluoromethyl-2,2,2-trifluoroethyl group, 3-fluoropropyl group, 3,3,3-trifluoropropyl group, 2, 2,3,3,3-pentafluoropropyl, 3-chloropropyl, 4-fluorobutyl, 4-chloro Robutyl group, 5-fluoropentyl group, 5-chloropentyl group, 6-fluorohexyl group, 6-chlorohexyl group, 7-fluoroheptyl group, 7-chloroheptyl group, 8-fluorooctyl group, 8-chlorooctyl group ,
Methoxymethyl group, ethoxymethyl group, propoxymethyl group, (2-methylethoxy) methyl group, dimethoxymethyl group, diethoxymethyl group, 1-methoxyethyl group, 2-methoxyethyl group, 2,2-dimethoxyethyl group, 2-ethoxyethyl group, 2-propoxyethyl group, 3-methoxypropyl group, 3-ethoxypropyl group, 3-propoxypropyl group, 4-methoxybutyl group, 4-ethoxybutyl group, 4-propoxybutyl group, 5- Methoxypentyl group, 5-ethoxypentyl group, 5-propoxypentyl group, 6-methoxyhexyl group, 6-ethoxyhexyl group, 6-propoxyhexyl group, 7-methoxyheptyl group, 7-ethoxyheptyl group, 7-propoxyheptyl Group, 8-methoxyoctyl group, 8-ethoxyoctyl group and 8-group Pokishiokuchiru group, and the like.
Examples of the C1-C8 alkoxy group substituted with one or more groups selected from the group consisting of a halogen atom represented by R 2 and a C1-C3 alkoxy group include a trifluoromethoxy group, a 1-fluoroethoxy group, 2 -Fluoroethoxy group, 2-chloroethoxy group, 2-bromoethoxy group, 2,2,2-trifluoroethoxy group, pentafluoroethoxy group, 1-trifluoromethyl-2,2,2-trifluoroethoxy group, 3-fluoropropoxy group, 3,3,3-trifluoropropoxy group, 2,2,3,3,3-pentafluoropropoxy group, 3-chloropropoxy group, 4-fluorobutoxy group, 4-chlorobutoxy group, 5-fluoropentyloxy group, 5-chloropentyloxy group, 6-fluorohexyloxy group, 6-chlorohexyl Oxy group, 7-fluoroheptyloxy group, 7-chloroheptyloxy group, 8-fluorooctyloxy group, 8-chlorooctyloxy group,
Methoxymethoxy group, ethoxymethoxy group, 2-methoxyethoxy group, 2,2-dimethoxyethoxy group, 2-ethoxyethoxy group, 2-propoxyethoxy group, 3-methoxypropoxy group, 3-ethoxypropoxy group, 3-propoxypropoxy group Group, 4-methoxybutoxy group, 4-ethoxybutoxy group, 4-propoxybutoxy group, 5-methoxypentyloxy group, 5-ethoxypentyloxy group, 5-propoxypentyloxy group, 6-methoxyhexyloxy group, 6- Ethoxyhexyloxy group, 6-propoxyhexyloxy group, 7-methoxyheptyloxy group, 7-ethoxyheptyloxy group, 7-propoxyheptyloxy group, 8-methoxyoctyloxy group, 8-ethoxyoctyloxy group and 8-propoxy group Octyloxy group And the like.
Examples of the C3-C9 alkenyloxy group substituted with one or more groups selected from the group consisting of a halogen atom represented by R 2 and a C1-C3 alkoxy group include a 3,3-difluoro-2-propenyloxy group. 2-chloro-2-propenyloxy group, 3-chloro-2-propenyloxy group, 3,3-dichloro-2-propenyloxy group, 2,3,3-trichloro-2-propenyloxy group, 4-chloro -2-butenyloxy group, 4-bromo-2-butenyloxy group, 4-methoxy-2-butenyloxy group, 4-ethoxy-2-butenyloxy group, 3-chloro-3-butenyloxy group, 5-chloro-2-pentenyloxy Group, 5-bromo-2-pentenyloxy group, 5-methoxy-2-pentenyloxy group, 5-chloro-3-pentenyloxy group Si group, 5-bromo-3-pentenyloxy group, 5-methoxy-3-pentenyloxy group, 6-chloro-3-hexenyloxy group, 6-bromo-3-hexenyloxy group, 6-methoxy-3-hexenyl Oxy group, 6-chloro-4-hexenyloxy group, 6-bromo-4-hexenyloxy group, 6-methoxy-4-hexenyloxy group, 7-chloro-3-heptenyloxy group, 7-bromo-3-heptenyloxy group 7-methoxy-3-heptenyloxy group, 7-chloro-4-heptenyloxy group, 7-bromo-4-heptenyloxy group, 7-methoxy-4-heptenyloxy group, 7-chloro-5-heptenyloxy group, 7-bromo- 5-heptenyloxy group, 7-methoxy-5-heptenyloxy group, 8-chloro-3-octenyloxy group, -Bromo-3-octenyloxy group, 8-methoxy-3-octenyloxy group, 8-chloro-4-octenyloxy group, 8-bromo-4-octenyloxy group, 8-methoxy-4-octyl group Examples thereof include a tenenyloxy group, an 8-chloro-5-octenyloxy group, an 8-bromo-5-octenyloxy group, and an 8-methoxy-5-octenyloxy group.
Examples of the C3-C9 alkynyloxy group substituted with one or more groups selected from the group consisting of a halogen atom represented by R 2 and a C1-C3 alkoxy group include a 4-chloro-2-butynyloxy group, 4- Bromo-2-butynyloxy group, 4-methoxy-2-butynyloxy group, 5-chloro-2-pentynyloxy group, 5-bromo-2-pentynyloxy group, 5-methoxy-2-pentynyloxy group, 5 -Chloro-3-pentynyloxy group, 5-bromo-3-pentynyloxy group, 5-methoxy-3-pentynyloxy group, 6-chloro-3-hexynyloxy group, 6-bromo-3-hexynyloxy group, 6-methoxy-3-hexynyloxy group, 6-chloro-4-hexynyloxy group, 6-bromo-4-hexynyloxy group, 6-methoxy- 4-hexynyloxy group, 7-chloro-3-heptynyloxy group, 7-bromo-3-heptynyloxy group, 7-methoxy-3-heptynyloxy group, 7-chloro-4-heptynyloxy group, 7-bromo-4-heptynyloxy group, 7-methoxy-4-heptynyloxy group, 7-chloro-5-heptynyloxy group, 7-bromo-5-heptynyloxy group, 7-methoxy-5-heptynyloxy group, 8-chloro-3-octynyloxy group, 8-bromo-3 -Octynyloxy group, 8-methoxy-3-octynyloxy group, 8-chloro-4-octynyloxy group, 8-bromo-4-octynyloxy group, 8-methoxy-4-octynyloxy group, 8-chloro-5-octynyloxy group, 8 -Bromo-5-octynyloxy group, 8-methoxy-5-o Chiniruokishi group, 8-chloro-6-Okuchiniruokishi groups include 8-bromo-6-Okuchiniruokishi group and 8-methoxy-6-Okuchiniruokishi group.
Examples of the (C3-C8 cycloalkyl) C1-C6 alkoxy group substituted with one or more groups selected from the group consisting of a halogen atom represented by R 2 and a C1-C3 alkoxy group include (2,2- (Dichlorocyclopropyl) methoxy group, 2- (2,2-dichlorocyclopropyl) ethoxy group, (3-chlorocyclopentyl) methoxy group, (3-methoxycyclopentyl) methoxy group, (4-chlorocyclopentyl) methoxy group, (4 -Methoxycyclopentyl) methoxy group, (3-chlorocyclohexyl) methoxy group, (3-methoxycyclohexyl) methoxy group, (4-chlorocyclohexyl) methoxy group, (4-methoxycyclohexyl) methoxy group and the like.
Halogen atom represented by R 2, as the C1-C3 alkyl group, C1-C3 alkoxy groups and one or more C6-C10 aryloxy group substituted by a group selected from the group consisting of a trifluoromethyl group, e.g. 2-fluorophenoxy group, 3-fluorophenoxy group, 4-fluorophenoxy group, 2,4-difluorophenoxy group, 3,4-difluorophenoxy group, 2-chlorophenoxy group, 3-chlorophenoxy group, 4-chlorophenoxy group Group, 3,4-dichlorophenoxy group, 2-methylphenoxy group, 3-methylphenoxy group, 4-methylphenoxy group, 3,5-dimethylphenoxy group, 4-bromophenoxy group, 3-ethylphenoxy group, 4- Ethylphenoxy group, 3-propylphenoxy group, 4-propylphenoxy group, 2-methyl Toxiphenoxy group, 3-methoxyphenoxy group, 4-methoxyphenoxy group, 3,4-dimethoxyphenoxy group, 3-ethoxyphenoxy group, 4-ethoxyphenoxy group, 3-propoxyphenoxy group, 4-propoxyphenoxy group, 2- Trifluoromethylphenoxy group, 3-trifluoromethylphenoxy group, 4-trifluoromethylphenoxy group, 2-chloro-4-trifluoromethylphenoxy group, 2-fluoro-3-methoxy group and 2-fluoro-4-methoxy Groups.
　本発明化合物の態様としては、例えば以下のものが挙げられる。
式（Ｉ）において、Ａが６－キノリル基であるアニリド化合物；
式（Ｉ）において、Ａがベンゾチアゾール－６－イル基であるアニリド化合物；
式（Ｉ）において、Ａが［１，５］ナフチリジン－２－イル基であるアニリド化合物；
式（Ｉ）において、ｎが０または１であるアニリド化合物；
式（Ｉ）において、Ｒ１がハロゲン原子であるアニリド化合物；
式（Ｉ）において、Ｒ１が塩素原子であるアニリド化合物；
式（Ｉ）において、Ｒ１がフッ素原子であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がハロゲン原子であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１が塩素原子であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がフッ素原子であるアニリド化合物； As an aspect of this invention compound, the following are mentioned, for example.
An anilide compound represented by formula (I), wherein A is a 6-quinolyl group;
An anilide compound represented by formula (I), wherein A is a benzothiazol-6-yl group;
An anilide compound represented by formula (I), wherein A is a [1,5] naphthyridin-2-yl group;
An anilide compound in which n is 0 or 1 in formula (I);
An anilide compound in which R 1 is a halogen atom in formula (I);
An anilide compound in which R 1 is a chlorine atom in formula (I);
An anilide compound represented by formula (I), wherein R 1 is a fluorine atom;
An anilide compound represented by the formula (I), wherein n is 1 and R 1 is a halogen atom;
An anilide compound represented by the formula (I), wherein n is 1 and R 1 is a chlorine atom;
An anilide compound in which n is 1 and R 1 is a fluorine atom in formula (I);
式（Ｉ）において、Ｒ２がベンゼン環の４位に置換したアニリド化合物（下式（Ｉ－ａ）
Figure JPOXMLDOC01-appb-C000003
 〔式中、Ａ、ｎ、Ｒ１及びＲ２は前記と同じ意味を表す。〕
で示されるアニリド化合物）；
式（Ｉ）において、Ｒ２がベンゼン環の３位に置換したアニリド化合物（下式（Ｉ－ｂ）
Figure JPOXMLDOC01-appb-C000004
 〔式中、Ａ、ｎ、Ｒ１及びＲ２は前記と同じ意味を表す。〕
で示されるアニリド化合物）；
式（Ｉ）において、Ａが６－キノリル基であり、Ｒ２がベンゼン環の４位に置換したアニリド化合物；
式（Ｉ）において、Ａが６－キノリル基であり、Ｒ２がベンゼン環の３位に置換したアニリド化合物；
式（Ｉ）において、Ａがベンゾチアゾール－６－イル基であり、Ｒ２がベンゼン環の４位に置換したアニリド化合物；
式（Ｉ）において、Ａがベンゾチアゾール－６－イル基であり、Ｒ２がベンゼン環の３位に置換したアニリド化合物；
式（Ｉ）において、Ａが［１，５］ナフチリジン－２－イル基であり、Ｒ２がベンゼン環の４位に置換したアニリド化合物；
式（Ｉ）において、Ａが［１，５］ナフチリジン－２－イル基であり、Ｒ２がベンゼン環の３位に置換したアニリド化合物；
式（Ｉ）において、Ｒ１がフッ素原子であり、Ｒ２がベンゼン環の４位に置換したアニリド化合物；
式（Ｉ）において、Ｒ１がフッ素原子であり、Ｒ２がベンゼン環の３位に置換したアニリド化合物； An anilide compound in which R 2 is substituted at the 4-position of the benzene ring in the formula (I) (the following formula (Ia)
Figure JPOXMLDOC01-appb-C000003
 [Wherein, A, n, R 1 and R 2 represent the same meaning as described above. ]
Anilide compound represented by:
In formula (I), an anilide compound wherein R 2 is substituted at the 3-position of the benzene ring (following formula (Ib)
Figure JPOXMLDOC01-appb-C000004
 [Wherein, A, n, R 1 and R 2 represent the same meaning as described above. ]
Anilide compound represented by:
An anilide compound in which A is a 6-quinolyl group and R 2 is substituted at the 4-position of the benzene ring in formula (I);
An anilide compound in which A is a 6-quinolyl group and R 2 is substituted at the 3-position of the benzene ring in formula (I);
In formula (I), an anilide compound in which A is a benzothiazol-6-yl group and R 2 is substituted at the 4-position of the benzene ring;
In formula (I), an anilide compound in which A is a benzothiazol-6-yl group and R 2 is substituted at the 3-position of the benzene ring;
In formula (I), an anilide compound in which A is a [1,5] naphthyridin-2-yl group and R 2 is substituted at the 4-position of the benzene ring;
In formula (I), an anilide compound in which A is a [1,5] naphthyridin-2-yl group and R 2 is substituted at the 3-position of the benzene ring;
An anilide compound in which R 1 is a fluorine atom and R 2 is substituted at the 4-position of the benzene ring in formula (I);
An anilide compound in which R 1 is a fluorine atom and R 2 is substituted at the 3-position of the benzene ring in formula (I);
式（Ｉ）において、Ｒ２がハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ１－８アルキル基であるアニリド化合物；
式（Ｉ）において、Ｒ２がＣ１－８アルキル基であるアニリド化合物；
式（Ｉ）において、Ｒ２がハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ１－８アルコキシ基であるアニリド化合物；
式（Ｉ）において、Ｒ２がＣ１－８アルコキシ基であるアニリド化合物；
式（Ｉ）において、Ｒ２がハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ３－９アルケニルオキシ基であるアニリド化合物；
式（Ｉ）において、Ｒ２がＣ３－９アルケニルオキシ基であるアニリド化合物；
式（Ｉ）において、Ｒ２がハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ３－９アルキニルオキシ基であるアニリド化合物；
式（Ｉ）において、Ｒ２Ｃ３－９アルキニルオキシ基であるアニリド化合物；
式（Ｉ）において、Ｒ２がハロゲン原子、Ｃ１－３アルキル基、Ｃ１－３アルコキシ基及びトリフルオロメチル基からなる群より選ばれる１種以上の基で置換されていてもよいＣ６－１０アリールオキシ基であるアニリド化合物；
式（Ｉ）において、Ｒ２がＣ６－１０アリールオキシ基であるアニリド化合物；
式（Ｉ）において、Ｒ２がハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよい（Ｃ３－８シクロアルキル）Ｃ１－６アルコキシ基であるアニリド化合物；
式（Ｉ）において、Ｒ２が（Ｃ３－８シクロアルキル）Ｃ１－６アルコキシ基であるアニリド化合物； An anilide compound in which R 2 in formula (I) is a C1-8 alkyl group optionally substituted by one or more groups selected from the group consisting of a halogen atom and a C1-3 alkoxy group;
An anilide compound represented by the formula (I), wherein R 2 is a C1-8 alkyl group;
An anilide compound in which R 2 in formula (I) is a C1-8 alkoxy group optionally substituted with one or more groups selected from the group consisting of a halogen atom and a C1-3 alkoxy group;
An anilide compound represented by the formula (I), wherein R 2 is a C1-8 alkoxy group;
An anilide compound in which R 2 in formula (I) is a C3-9 alkenyloxy group optionally substituted by one or more groups selected from the group consisting of a halogen atom and a C1-3 alkoxy group;
An anilide compound represented by the formula (I), wherein R 2 is a C3-9 alkenyloxy group;
An anilide compound in which R 2 in formula (I) is a C3-9 alkynyloxy group optionally substituted by one or more groups selected from the group consisting of a halogen atom and a C1-3 alkoxy group;
An anilide compound which is an R 2 C3-9 alkynyloxy group in formula (I);
In the formula (I), R 2 is a C6-10 aryl optionally substituted with one or more groups selected from the group consisting of a halogen atom, a C1-3 alkyl group, a C1-3 alkoxy group, and a trifluoromethyl group. An anilide compound which is an oxy group;
An anilide compound represented by the formula (I), wherein R 2 is a C6-10 aryloxy group;
In formula (I), anilide wherein R 2 is a (C3-8 cycloalkyl) C1-6 alkoxy group optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-3 alkoxy groups Compound;
An anilide compound represented by the formula (I), wherein R 2 is a (C3-8 cycloalkyl) C1-6 alkoxy group;
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であるアニリド化合物（下式（Ｉ－ｃ）
Figure JPOXMLDOC01-appb-C000005
 〔式中、Ａ、ｎ及びＲ２は前記と同じ意味を表す。〕
で示される化合物）； In the formula (I), an anilide compound wherein n is 1 and R 1 is a fluorine atom substituted at the 2-position of the benzene ring (the following formula (Ic)
Figure JPOXMLDOC01-appb-C000005
 [Wherein, A, n and R 2 represent the same meaning as described above. ]
A compound represented by:
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したアニリド化合物（下式（Ｉ－ｄ）
Figure JPOXMLDOC01-appb-C000006
 〔式中、Ａ及びｎは前記と同じ意味を表し、Ｒ２ｄはＣ１－Ｃ８アルキル基、Ｃ１－Ｃ８アルコキシ基、Ｃ３－Ｃ９アルケニルオキシ基、Ｃ３－Ｃ９アルキニルオキシ基、Ｃ６－Ｃ１０アリールオキシ基又は（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルコキシ基を表す。
但し、該Ｒ２ｄで示されるＣ１－Ｃ８アルキル基、Ｃ１－Ｃ８アルコキシ基、Ｃ３－Ｃ９アルケニルオキシ基、Ｃ３－Ｃ９アルキニルオキシ基及び（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルコキシ基は、いずれもハロゲン原子及びＣ１－Ｃ３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよく、
また、該Ｒ２ｄで示されるＣ６－Ｃ１０アリールオキシ基は、ハロゲン原子、Ｃ１－Ｃ３アルキル基、Ｃ１－Ｃ３アルコキシ基及びトリフルオロメチル基からなる群より選ばれる１種以上の基で置換されていてもよい。〕
で示される化合物）； In formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is substituted at the 4-position of the benzene ring (following formula (Id)
Figure JPOXMLDOC01-appb-C000006
 [Wherein, A and n represent the same meaning as described above, and R 2d represents a C1-C8 alkyl group, a C1-C8 alkoxy group, a C3-C9 alkenyloxy group, a C3-C9 alkynyloxy group, a C6-C10 aryloxy group. Or a (C3-C8 cycloalkyl) C1-C6 alkoxy group.
However, the C1-C8 alkyl group, the C1-C8 alkoxy group, the C3-C9 alkenyloxy group, the C3-C9 alkynyloxy group and the (C3-C8 cycloalkyl) C1-C6 alkoxy group represented by R 2d are all May be substituted with one or more groups selected from the group consisting of a halogen atom and a C1-C3 alkoxy group,
The C6-C10 aryloxy group represented by R 2d is substituted with one or more groups selected from the group consisting of a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group and a trifluoromethyl group. May be. ]
A compound represented by:
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したアニリド化合物（下式（Ｉ－ｄ）；
Figure JPOXMLDOC01-appb-C000007
 〔式中、Ａ及びｎは前記と同じ意味を表し、Ｒ２ｅはＣ１－Ｃ８アルキル基、Ｃ１－Ｃ８アルコキシ基、Ｃ３－Ｃ９アルケニルオキシ基、Ｃ３－Ｃ９アルキニルオキシ基、Ｃ６－Ｃ１０アリールオキシ基又は（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルコキシ基を表す。
但し、該Ｒ２ｅで示されるＣ１－Ｃ８アルキル基、Ｃ１－Ｃ８アルコキシ基、Ｃ３－Ｃ９アルケニルオキシ基、Ｃ３－Ｃ９アルキニルオキシ基及び（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルコキシ基は、いずれもハロゲン原子及びＣ１－Ｃ３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよく、
また、該Ｒ２ｅで示されるＣ６－Ｃ１０アリールオキシ基は、ハロゲン原子、Ｃ１－Ｃ３アルキル基、Ｃ１－Ｃ３アルコキシ基及びトリフルオロメチル基からなる群より選ばれる１種以上の基で置換されていてもよい。〕
で示される化合物）； In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is substituted at the 3-position of the benzene ring (the following formula (Id);
Figure JPOXMLDOC01-appb-C000007
 [Wherein, A and n represent the same meaning as described above, and R 2e represents a C1-C8 alkyl group, a C1-C8 alkoxy group, a C3-C9 alkenyloxy group, a C3-C9 alkynyloxy group, a C6-C10 aryloxy group. Or a (C3-C8 cycloalkyl) C1-C6 alkoxy group.
However, the C1-C8 alkyl group, C1-C8 alkoxy group, C3-C9 alkenyloxy group, C3-C9 alkynyloxy group and (C3-C8 cycloalkyl) C1-C6 alkoxy group represented by R 2e are all May be substituted with one or more groups selected from the group consisting of a halogen atom and a C1-C3 alkoxy group,
The C6-C10 aryloxy group represented by R 2e is substituted with one or more groups selected from the group consisting of a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group and a trifluoromethyl group. May be. ]
A compound represented by:
式（Ｉ）において、Ａが６－キノリル基であり、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したアニリド化合物；
式（Ｉ）において、Ａが６－キノリル基であり、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したアニリド化合物；
式（Ｉ）において、Ａがベンゾチアゾール－６－イル基であり、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したアニリド化合物；
式（Ｉ）において、Ａがベンゾチアゾール－６－イル基であり、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したアニリド化合物；
式（Ｉ）において、Ａが［１，５］ナフチリジン－２－イル基であり、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したアニリド化合物；
式（Ｉ）において、Ａが［１，５］ナフチリジン－２－イル基であり、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したアニリド化合物； In formula (I), A is a 6-quinolyl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is substituted at the 4-position of the benzene ring ;
In formula (I), A is a 6-quinolyl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is substituted at the 3-position of the benzene ring ;
In the formula (I), A is a benzothiazol-6-yl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is substituted at the 4-position of the benzene ring An anilide compound;
In formula (I), A is a benzothiazol-6-yl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is substituted at the 3-position of the benzene ring An anilide compound;
In the formula (I), A is a [1,5] naphthyridin-2-yl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a benzene ring An anilide compound substituted in the 4-position;
In the formula (I), A is a [1,5] naphthyridin-2-yl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a benzene ring An anilide compound substituted in the 3-position;
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ１－８アルキル基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したＣ１－８アルキル基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ１－８アルコキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したＣ１－８アルコキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ３－９アルケニルオキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したＣ３－９アルケニルオキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ３－９アルキニルオキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したＣ３－９アルキニルオキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したハロゲン原子、Ｃ１－３アルキル基、Ｃ１－３アルコキシ基及びトリフルオロメチル基からなる群より選ばれる１種以上の基で置換されていてもよいＣ６－１０アリールオキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したＣ６－１０アリールオキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ３－８シクロアルキルＣ１－６アルコキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の４位に置換したＣ３－８シクロアルキルＣ１－６アルコキシ基であるアニリド化合物； In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a group consisting of a halogen atom substituted at the 4-position of the benzene ring and a C1-3 alkoxy group An anilide compound which is a C1-8 alkyl group which may be substituted with one or more groups selected from;
In formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C1-8 alkyl group substituted at the 4-position of the benzene ring;
In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a group consisting of a halogen atom substituted at the 4-position of the benzene ring and a C1-3 alkoxy group An anilide compound which is a C1-8 alkoxy group optionally substituted with one or more groups selected from the group;
In formula (I), an anilide compound in which n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C1-8 alkoxy group substituted at the 4-position of the benzene ring;
In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a group consisting of a halogen atom substituted at the 4-position of the benzene ring and a C1-3 alkoxy group An anilide compound which is a C3-9 alkenyloxy group optionally substituted by one or more selected from the group;
In formula (I), an anilide compound in which n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C3-9 alkenyloxy group substituted at the 4-position of the benzene ring;
In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a group consisting of a halogen atom substituted at the 4-position of the benzene ring and a C1-3 alkoxy group An anilide compound which is a C3-9 alkynyloxy group optionally substituted with one or more groups selected from:
In formula (I), an anilide compound in which n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C3-9 alkynyloxy group substituted at the 4-position of the benzene ring;
In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, R 2 is a halogen atom substituted at the 4-position of the benzene ring, a C1-3 alkyl group, C1- An anilide compound which is a C6-10 aryloxy group optionally substituted with one or more groups selected from the group consisting of 3 alkoxy groups and trifluoromethyl groups;
An anilide compound represented by formula (I), wherein n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C6-10 aryloxy group substituted at the 4-position of the benzene ring;
In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a group consisting of a halogen atom substituted at the 4-position of the benzene ring and a C1-3 alkoxy group An anilide compound which is a C3-8 cycloalkyl C1-6 alkoxy group optionally substituted with one or more groups selected from;
In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C3-8 cycloalkyl C1-6 alkoxy group substituted at the 4-position of the benzene ring. An anilide compound;
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ１－８アルキル基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したＣ１－８アルキル基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ１－８アルコキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したＣ１－８アルコキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ３－９アルケニルオキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したＣ３－９アルケニルオキシ基であるアニリド化合物； In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, R 2 is a group consisting of a halogen atom substituted at the 3-position of the benzene ring and a C1-3 alkoxy group An anilide compound which is a C1-8 alkyl group optionally substituted with one or more groups selected from the group;
In formula (I), an anilide compound in which n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C1-8 alkyl group substituted at the 3-position of the benzene ring;
In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, R 2 is a group consisting of a halogen atom substituted at the 3-position of the benzene ring and a C1-3 alkoxy group An anilide compound which is a C1-8 alkoxy group optionally substituted with one or more groups selected from the group;
In formula (I), an anilide compound in which n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C1-8 alkoxy group substituted at the 3-position of the benzene ring;
In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, R 2 is a group consisting of a halogen atom substituted at the 3-position of the benzene ring and a C1-3 alkoxy group An anilide compound which is a C3-9 alkenyloxy group optionally substituted with one or more groups selected from the group;
In formula (I), an anilide compound in which n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C3-9 alkenyloxy group substituted at the 3-position of the benzene ring;
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ３－９アルキニルオキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したＣ３－９アルキニルオキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したハロゲン原子、Ｃ１－３アルキル基、Ｃ１－３アルコキシ基及びトリフルオロメチル基からなる群より選ばれる１種以上の基で置換されていてもよいＣ６－１０アリールオキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したＣ６－１０アリールオキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したハロゲン原子及びＣ１－３アルコキシ基からなる群より選ばれる１種以上の基で置換されていてもよいＣ３－８シクロアルキルＣ１－６アルコキシ基であるアニリド化合物；
式（Ｉ）において、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したＣ３－８シクロアルキルＣ１－６アルコキシ基であるアニリド化合物。 In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, R 2 is a group consisting of a halogen atom substituted at the 3-position of the benzene ring and a C1-3 alkoxy group An anilide compound which is a C3-9 alkynyloxy group optionally substituted with one or more groups selected from:
An anilide compound represented by the formula (I), wherein n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C3-9 alkynyloxy group substituted at the 3-position of the benzene ring;
In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, R 2 is a halogen atom substituted at the 3-position of the benzene ring, a C1-3 alkyl group, C1- An anilide compound which is a C6-10 aryloxy group optionally substituted with one or more groups selected from the group consisting of 3 alkoxy groups and trifluoromethyl groups;
In formula (I), an anilide compound in which n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C6-10 aryloxy group substituted at the 3-position of the benzene ring;
In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, R 2 is a group consisting of a halogen atom substituted at the 3-position of the benzene ring and a C1-3 alkoxy group An anilide compound which is a C3-8 cycloalkyl C1-6 alkoxy group optionally substituted with one or more groups selected from;
In the formula (I), n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a C3-8 cycloalkyl C 1-6 alkoxy group substituted at the 3-position of the benzene ring. An anilide compound.
　本発明化合物は、例えば以下の（製造法１）～（製造法３）により製造することができる。 The compound of the present invention can be produced, for example, by the following (Production Method 1) to (Production Method 3).
（製造法１）
　本発明化合物は、化合物（ＩＩ）、化合物（ＩＩＩ）及び縮合剤の存在下に反応させることにより製造することができる。
Figure JPOXMLDOC01-appb-C000008
 〔式中、Ａ、ｎ、Ｒ１及びＲ２は前記と同じ意味を表す。〕
　該反応は、通常溶媒の存在下で行われる。
　反応に用いられる溶媒としては、例えばテトラヒドロフラン（以下、ＴＨＦと記す。）、エチレングリコールジメチルエーテル、ｔｅｒｔ－ブチルメチルエーテル（以下、ＭＴＢＥと記す。）等のエーテル類、ヘキサン、へプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸ブチル、酢酸エチル等のエステル類、アセトニトリル等のニトリル類、Ｎ，Ｎ－ジメチルホルムアミド（以下、ＤＭＦと記す。）等の酸アミド類、ジメチルスルホキシド（以下、ＤＭＳＯと記す。）等のスルホキシド類及びこれらの混合物が挙げられる。
　該反応に用いられる縮合剤としては、１－エチル－３－（３－ジメチルアミノプロピル）カルボジイミド塩酸塩（以下、ＷＳＣと記す。）及び１，３－ジシクロヘキシルカルボジイミド等のカルボジイミド類、（ベンゾトリアゾール－１－イルオキシ）トリス（ジメチルアミノ）ホスホニウムヘキサフルオロホスフェート（以下、ＢＯＰ試薬と記す。）等が挙げられる。
　該反応には化合物（ＩＩ）１モルに対して、化合物（ＩＩＩ）が通常１～３モルの割合、縮合剤が通常１～５モルの割合で用いられる。
　該反応の反応温度は、通常０～１４０℃の範囲である。該反応の反応時間は通常１～２４時間の範囲である。
　反応終了後は、反応混合物を濾過した後、濾液を有機溶媒で抽出し、有機層を乾燥、濃縮する等の後処理操作を行うことにより、本発明化合物を単離することができる。単離された本発明化合物は、クロマトグラフィー、再結晶等によりさらに精製することもできる。 (Production method 1)
The compound of the present invention can be produced by reacting in the presence of compound (II), compound (III) and a condensing agent.
Figure JPOXMLDOC01-appb-C000008
 [Wherein, A, n, R 1 and R 2 represent the same meaning as described above. ]
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as tetrahydrofuran (hereinafter referred to as THF), ethylene glycol dimethyl ether, tert-butyl methyl ether (hereinafter referred to as MTBE), and fats such as hexane, heptane, and octane. Aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as chlorobenzene, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, N, N-dimethylformamide (hereinafter, Acid amides such as DMF), sulfoxides such as dimethyl sulfoxide (hereinafter referred to as DMSO), and mixtures thereof.
Examples of the condensing agent used in the reaction include 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (hereinafter referred to as WSC) and carbodiimides such as 1,3-dicyclohexylcarbodiimide, (benzotriazole- 1-yloxy) tris (dimethylamino) phosphonium hexafluorophosphate (hereinafter referred to as BOP reagent) and the like.
In the reaction, with respect to 1 mol of compound (II), compound (III) is usually used in a proportion of 1 to 3 mol, and the condensing agent is usually used in a proportion of 1 to 5 mol.
The reaction temperature of the reaction is usually in the range of 0 to 140 ° C. The reaction time is usually in the range of 1 to 24 hours.
After completion of the reaction, the compound of the present invention can be isolated by performing post-treatment operations such as filtration of the reaction mixture, extraction of the filtrate with an organic solvent, and drying and concentration of the organic layer. The isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.
（製造法２）
　本発明化合物は、化合物（ＩＩ）と化合物（ＩＶ）又はその塩（例えば、塩酸塩が挙げられる。）とを、塩基の存在下、反応させることにより製造することができる。
Figure JPOXMLDOC01-appb-C000009
 〔式中、Ａ、ｎ、Ｒ１及びＲ２は前記と同じ意味を表す。〕
　該反応は、通常溶媒の存在下で行われる。
　該反応に用いられる溶媒としては、例えばＴＨＦ、エチレングリコールジメチルエーテル、ＭＴＢＥ等のエーテル類、ヘキサン、へプタン、オクタン等の脂肪族炭化水素類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、酢酸ブチル、酢酸エチル等のエステル類、アセトニトリル等のニトリル類、ＤＭＦ等の酸アミド類、ＤＭＳＯ等のスルホキシド類及びこれらの混合物が挙げられる。
　該反応に用いられる塩基としては、炭酸ナトリウム、炭酸カリウム等のアルカリ金属炭酸塩類、トリエチルアミン、ジイソプロピルエチルアミン等の第３級アミン類及びピリジン、４－ジメチルアミノピリジン等の含窒素芳香族化合物類等が挙げられる。
　該反応には化合物（ＩＩ）１モルに対して、化合物（ＩＶ）が通常１～３モルの割合、塩基が通常１～１０モルの割合で用いられる。
　該反応の反応温度は通常－２０～１００℃の範囲である。該反応の反応時間は通常０．１～２４時間の範囲である。
　反応終了後は、反応混合物を有機溶媒で抽出し、有機層を乾燥、濃縮する等の後処理操作を行うことにより、本発明化合物を単離することができる。単離された本発明化合物は、クロマトグラフィー、再結晶等によりさらに精製することもできる。 (Production method 2)
The compound of the present invention can be produced by reacting compound (II) with compound (IV) or a salt thereof (for example, hydrochloride) in the presence of a base.
Figure JPOXMLDOC01-appb-C000009
 [Wherein, A, n, R 1 and R 2 represent the same meaning as described above. ]
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aliphatic hydrocarbons such as hexane, heptane, and octane, aromatic hydrocarbons such as toluene and xylene, and chlorobenzene. Examples thereof include halogenated hydrocarbons, esters such as butyl acetate and ethyl acetate, nitriles such as acetonitrile, acid amides such as DMF, sulfoxides such as DMSO, and mixtures thereof.
Examples of the base used in the reaction include alkali metal carbonates such as sodium carbonate and potassium carbonate, tertiary amines such as triethylamine and diisopropylethylamine, and nitrogen-containing aromatic compounds such as pyridine and 4-dimethylaminopyridine. Can be mentioned.
In the reaction, with respect to 1 mol of compound (II), compound (IV) is usually used in a proportion of 1 to 3 mol, and base is usually used in a proportion of 1 to 10 mol.
The reaction temperature is usually in the range of −20 to 100 ° C. The reaction time is usually in the range of 0.1 to 24 hours.
After completion of the reaction, the compound of the present invention can be isolated by performing post-treatment operations such as extraction of the reaction mixture with an organic solvent, and drying and concentration of the organic layer. The isolated compound of the present invention can be further purified by chromatography, recrystallization and the like.
（製造法３）
　本発明化合物のうち化合物（ＶＩＩ）は、化合物（Ｖ）と化合物（ＶＩ）とを塩基の存在下に反応させることにより製造することができる。
Figure JPOXMLDOC01-appb-C000010
 〔式中、Ａ及びＲ１は前記と同じ意味を表し、Ｌは塩素原子、臭素原子、ヨウ素原子、メタンスルホニルオキシ基、トリフルオロメタンスルホニルオキシ基又はｐ－トルエンスルホニルオキシ基を表す。Ｒ２－１はベンゼン環の３位又は４位に置換したＣ１－Ｃ８アルキル基、Ｃ３－Ｃ９アルケニル基、Ｃ３－Ｃ９アルキニル基又は（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルキル基を表す。ここで、該Ｒ２－１で示されるＣ１－Ｃ８アルキル基、Ｃ３－Ｃ９アルケニル基、Ｃ３－Ｃ９アルキニル基及び（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルキル基は、ハロゲン原子及びＣ１－Ｃ３アルコキシ基からなる群より選ばれる１以上の基で置換されていてもよく、
また、該Ｒ２－１で示されるＣ６－Ｃ１０アリール基は、ハロゲン原子、Ｃ１－Ｃ３アルキル基、Ｃ１－Ｃ３アルコキシ基及びトリフルオロメチル基からなる群より選ばれる１以上の基で置換されていてもよい。〕
　該反応は、通常溶媒の存在下で行われる。
　該反応に用いられる溶媒としては、例えばＴＨＦ、エチレングリコールジメチルエーテル、ＭＴＢＥ等のエーテル類、トルエン、キシレン等の芳香族炭化水素類、クロロベンゼン等のハロゲン化炭化水素類、アセトニトリル等のニトリル類、ＤＭＦ等の酸アミド類、ＤＭＳＯ等のスルホキシド類、アセトン、メチルエチルケトン、メチルイソブチルケトン等のケトン類、水及びこれらの混合物が挙げられる。
　該反応に用いられる塩基としては、炭酸ナトリウム、炭酸カリウム、炭酸セシウム等のアルカリ金属炭酸塩類、水酸化ナトリウム等のアルカリ金属水酸化物類、水素化ナトリウム等のアルカリ金属水素化物類等が挙げられる。
　該反応には化合物（Ｖ）１モルに対して、化合物（ＶＩ）が通常１～１０モルの割合、塩基が通常１～５モルの割合で用いられる。
　該反応の反応温度は通常－２０～１００℃の範囲である。該反応の反応時間は通常０．１～２４時間の範囲である。
　反応終了後は、反応混合物に水を加えた際に固体が析出した場合は、濾過により固体を集めることにより化合物（ＶＩＩ）を単離することができる。また、反応混合物に水を加えた際に固体が析出しない場合は、反応混合物を有機溶媒で抽出し、有機層を乾燥、濃縮する等の後処理操作を行うことにより、化合物（ＶＩＩ）を単離することができる。単離された化合物（ＶＩＩ）は、クロマトグラフィー、再結晶等によりさらに精製することもできる。 (Production method 3)
Among the compounds of the present invention, compound (VII) can be produced by reacting compound (V) with compound (VI) in the presence of a base.
Figure JPOXMLDOC01-appb-C000010
 [Wherein, A and R 1 represent the same meaning as described above, and L represents a chlorine atom, a bromine atom, an iodine atom, a methanesulfonyloxy group, a trifluoromethanesulfonyloxy group, or a p-toluenesulfonyloxy group. R 2-1 represents a C1-C8 alkyl group, a C3-C9 alkenyl group, a C3-C9 alkynyl group or a (C3-C8 cycloalkyl) C1-C6 alkyl group substituted at the 3-position or 4-position of the benzene ring. Here, C1-C8 alkyl group represented by the R 2-1, C3-C9 alkenyl group, C3-C9 alkynyl and (C3-C8 cycloalkyl) C1-C6 alkyl group, a halogen atom and C1-C3 alkoxy May be substituted with one or more groups selected from the group consisting of groups,
The C6-C10 aryl group represented by R 2-1 is substituted with one or more groups selected from the group consisting of a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group and a trifluoromethyl group. May be. ]
The reaction is usually performed in the presence of a solvent.
Examples of the solvent used in the reaction include ethers such as THF, ethylene glycol dimethyl ether, and MTBE, aromatic hydrocarbons such as toluene and xylene, halogenated hydrocarbons such as chlorobenzene, nitriles such as acetonitrile, DMF, and the like. Acid amides, sulfoxides such as DMSO, ketones such as acetone, methyl ethyl ketone, and methyl isobutyl ketone, water, and mixtures thereof.
Examples of the base used in the reaction include alkali metal carbonates such as sodium carbonate, potassium carbonate and cesium carbonate, alkali metal hydroxides such as sodium hydroxide, alkali metal hydrides such as sodium hydride, and the like. .
In the reaction, with respect to 1 mole of the compound (V), the compound (VI) is usually used in a proportion of 1 to 10 moles, and the base is usually used in a proportion of 1 to 5 moles.
The reaction temperature is usually in the range of −20 to 100 ° C. The reaction time is usually in the range of 0.1 to 24 hours.
After completion of the reaction, when water is added to the reaction mixture and a solid is precipitated, the compound (VII) can be isolated by collecting the solid by filtration. In addition, when solid does not precipitate when water is added to the reaction mixture, post-treatment operations such as extraction of the reaction mixture with an organic solvent, drying and concentration of the organic layer, and the like can be carried out. Can be separated. The isolated compound (VII) can be further purified by chromatography, recrystallization and the like.
　本発明防除剤は、本発明化合物を固体担体、液体担体、ガス担体、界面活性剤等と混合し、必要により固着剤、分散剤、安定剤等の製剤用補助剤を添加して、水和剤、顆粒水和剤、フロアブル剤、粒剤、ドライフロアブル剤、乳剤、水性液剤、油剤、くん煙剤、エアゾール剤、マイクロカプセル剤等に製剤化して用いる。これらの製剤には本発明化合物が重量比で通常０．１～９９％、好ましくは０．２～９０％含有される。 The control agent of the present invention is prepared by mixing the compound of the present invention with a solid carrier, liquid carrier, gas carrier, surfactant, etc. It is formulated into an agent, granular wettable powder, flowable agent, granule, dry flowable agent, emulsion, aqueous liquid agent, oil agent, smoke agent, aerosol agent, microcapsule agent and the like. These preparations contain the compound of the present invention in a weight ratio of usually 0.1 to 99%, preferably 0.2 to 90%.
　固体担体としては、例えば、粘土類（例えば、カオリン、珪藻土、合成含水酸化珪素、フバサミクレー、ベントナイト、酸性白土）、タルク類、その他の無機鉱物（例えば、セリサイト、石英粉末、硫黄粉末、活性炭、炭酸カルシウム、水和シリカ）等の微粉末あるいは粒状物が挙げられ、液体担体としては、例えば、水、アルコール類（例えば、メタノール、エタノール）、ケトン類（例えば、アセトン、メチルエチルケトン）、芳香族炭化水素類（例えば、ベンゼン、トルエン、キシレン、エチルベンゼン、メチルナフタレン）、脂肪族炭化水素類（例えば、ｎ－ヘキサン、シクロヘキサノン、灯油）、エステル類（例えば、酢酸エチル、酢酸ブチル）、ニトリル類（例えば、アセトニトリル、イソブチルニトリル）、エーテル類（例えば、ジオキサン、ジイソプロピルエーテル）、酸アミド類（例えば、ＤＭＦ、ジメチルアセトアミド）、ハロゲン化炭化水素類（例えば、ジクロロエタン、トリクロロエチレン、四塩化炭素）等が挙げられる。 Examples of the solid carrier include clays (for example, kaolin, diatomaceous earth, synthetic hydrous silicon oxide, fusami clay, bentonite, acidic clay), talc, and other inorganic minerals (for example, sericite, quartz powder, sulfur powder, activated carbon, Examples of the liquid carrier include water, alcohols (for example, methanol, ethanol), ketones (for example, acetone, methyl ethyl ketone), aromatic carbonization, and the like. Hydrogen (eg, benzene, toluene, xylene, ethylbenzene, methylnaphthalene), aliphatic hydrocarbons (eg, n-hexane, cyclohexanone, kerosene), esters (eg, ethyl acetate, butyl acetate), nitriles (eg, , Acetonitrile, isobutylnitrile), ethers (eg If, dioxane, diisopropyl ether), acid amides (e.g., DMF, dimethylacetamide), halogenated hydrocarbons (e.g., dichloroethane, trichlorethylene, and carbon tetrachloride), and the like.
　界面活性剤としては、例えばアルキル硫酸エステル類、アルキルスルホン酸塩、アルキルアリールスルホン酸塩、アルキルアリールエーテル類及びそのポリオキシエチレン化物、ポリオキシエチレングリコールエーテル類、多価アルコールエステル類、糖アルコール誘導体等が挙げられる。 Examples of the surfactant include alkyl sulfates, alkyl sulfonates, alkyl aryl sulfonates, alkyl aryl ethers and polyoxyethylene compounds thereof, polyoxyethylene glycol ethers, polyhydric alcohol esters, sugar alcohol derivatives. Etc.
　その他の製剤用補助剤としては、例えば固着剤や分散剤、具体的にはカゼイン、ゼラチン、多糖類（例えば、デンプン、アラビヤガム、セルロース誘導体、アルギン酸）、リグニン誘導体、ベントナイト、糖類、合成水溶性高分子（例えば、ポリビニルアルコール、ポリビニルピロリドン、ポリアクリル酸類）、ＰＡＰ（酸性りん酸イソプロピル）、ＢＨＴ（２，６－ジ－ｔｅｒｔ－ブチル－４－メチルフェノール）、ＢＨＡ（２－ｔｅｒｔ－ブチル－４－メトキシフェノールと３－ｔｅｒｔ－ブチル－４－メトキシフェノールとの混合物）、植物油、鉱物油、脂肪酸又はそのエステル等が挙げられる。 Other formulation adjuvants include, for example, fixing agents and dispersants, specifically casein, gelatin, polysaccharides (eg starch, arabic gum, cellulose derivatives, alginic acid), lignin derivatives, bentonite, saccharides, synthetic water-soluble high Molecules (eg, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylic acids), PAP (isopropyl acid phosphate), BHT (2,6-di-tert-butyl-4-methylphenol), BHA (2-tert-butyl-4 -Mixylphenol and 3-tert-butyl-4-methoxyphenol), vegetable oils, mineral oils, fatty acids or esters thereof.
　本発明防除剤を施用する方法としては、実質的に本発明防除剤が施用され得る形態であればその方法は特に限定されないが、例えば茎葉散布等の植物体への処理、土壌処理等の植物の栽培地への処理、種子消毒等の種子への処理等が挙げられる。 The method of applying the control agent of the present invention is not particularly limited as long as the control agent of the present invention can be applied substantially. And the like, and the treatment of seeds such as seed disinfection.
　また、本発明防除剤を他の殺菌剤、殺虫剤、殺ダニ剤、殺線虫剤、除草剤、植物生長調節剤、肥料または土壌改良剤と混合して、または混合せずに同時に用いることもできる。
かかる他の殺菌剤としては、例えば、プロピコナゾール、プロチオコナゾール、トリアジメノール、プロクロラズ、ペンコナゾール、テブコナゾール、フルシラゾール、ジニコナゾール、ブロムコナゾール、エポキシコナゾール、ジフェノコナゾール、シプロコナゾール、メトコナゾール、トリフルミゾール、テトラコナゾール、マイクロブタニル、フェンブコナゾール、ヘキサコナゾール、フルキンコナゾール、トリティコナゾール、ビテルタノール、イマザリル、フルトリアホール、シメコナゾール、イプコナゾール等のアゾール系殺菌化合物；フェンプロピモルフ、トリデモルフ、フェンプロピジン等の環状アミン系殺菌化合物；カルベンダジム、ベノミル、チアベンダゾール、チオファネートメチル等のベンズイミダゾール系殺菌化合物；プロシミドン；シプロディニル；ピリメタニル；ジエトフェンカルブ；チウラム；フルアジナム；マンコゼブ；イプロジオン；ビンクロゾリン；クロロタロニル；キャプタン；メパニピリム；フェンピクロニル；フルジオキソニル；ジクロフルアニド；フォルペット；クレソキシムメチル；アゾキシストロビン；トリフロキシストロビン；フルオキサストロビン；ピコキシストロビン；ピラクロストロビン；ジモキシストロビン；ピリベンカルブ；メトミノストロビン；エネストロビン；スピロキサミン；キノキシフェン；フェンヘキサミド；ファモキサドン；フェナミドン；ゾキサミド；エタボキサム；アミスルブロム；イプロヴァリカルブ；ベンチアバリカルブ；シアゾファミド；マンジプロパミド；ボスカリド；ペンチオピラド；メトラフェノン；フルオピラン；ビキサフェン；シフルフェナミド；プロキナジド；オリザストロビン；フラメトピル；チフルザミド；メプロニル；フルトラニル；フルスルファミド；フルオピコリド；メタラキシルＭ；キララキシル；フォセチル；シモキサニル；ペンシクロン；トルクロホスメチル；カルプロパミド；ジクロシメット；フェノキサニル；トリシクラゾール；ピロキロン；プロベナゾール；イソチアニル；チアジニル；テブフロキン；ジクロメジン；カスガマイシン；フェリムゾン；フサライド；バリダマイシン；ヒドロキシイソキサゾール；イミノクタジン酢酸塩；イソプロチオラン；オキソリニック酸；オキシテトラサイクリン；ストレプトマイシン；塩基性塩化銅；水酸化第二銅；塩基性硫酸銅；有機銅；硫黄；イソピラザムなどが挙げられる。 In addition, the present control agent may be used simultaneously with or without mixing with other fungicides, insecticides, acaricides, nematicides, herbicides, plant growth regulators, fertilizers or soil conditioners. You can also.
Such other fungicides include, for example, propiconazole, prothioconazole, triazimenol, prochloraz, penconazole, tebuconazole, flusilazole, diniconazole, bromconazole, epoxiconazole, difenoconazole, cyproconazole, metconazole, triflumi Azole fungicides such as sol, tetraconazole, microbutanyl, fenbuconazole, hexaconazole, fluquinconazole, triticonazole, viteltanol, imazalil, flutriahol, cimeconazole, ipconazole; fenpropimorph, tridemorph, Cyclic amine fungicides such as phenpropidin; benzimidazole fungicides such as carbendazim, benomyl, thiabendazole and thiophanate methyl Cyprodinil; Pyrimethanil; Diethofencarb; Thiuram; Fluazinam; Mancozeb; Iprodione; Vinclozoline; Chlorotalonyl; Captan; Mepanipyrim; Oxastrobin; picoxystrobin; pyraclostrobin; dimoxystrobin; pyribencarb; metminostrobin; enestrobine; spiroxamine; quinoxyphene; fenhexamide; famoxadone; fenamidone; zoxamide; ethaboxam; Avaricarb; Siazofamide; Mandipropamide; Boscalid; Penthiopyrad Metrafenone; fluopyran; bixafen; cyflufenamide; proquinazide; orizastrobin; furametopyr; tifluzamide; mepronil; flutolanil; flusulfamide; Probenazole; Isothianyl; Thiazinyl; Tebufloquine; Diclomedin; Kasugamycin; Ferimzone; Fusaride; Validamycin; Hydroxyisoxazole; Copper sulfate; organic copper; sulfur; iso Examples include pyrazam.
　かかる他の殺虫剤としては、例えば
（１）有機リン系化合物
アセフェート（acephate）、りん化アルミニウム（Aluminium phosphide）、ブタチオホス（butathiofos）、キャドサホス（cadusafos）、クロルエトキシホス（chlorethoxyfos）、クロルフェンビンホス（ch1orfenvinphos）、クロルピリホス（chlorpyrifos）、クロルピリホスメチル（chlorpyrifos-methyl）、シアノホス（cyanophos：CYAP）、ダイアジノン（diazinon）、ＤＣＩＰ（dichlorodiisopropyl ether）、ジクロフェンチオン（dichlofenthion：ECP）、ジクロルボス（dichlorvos：DDVP）、ジメトエート（dimethoate）、ジメチルビンホス（dimethylvinphos）、ジスルホトン（disulfoton）、EPN、エチオン（ethion）、エトプロホス（ethoprophos）、エトリムホス（etrimfos）、フェンチオン（fenthion：MPP）、フエニトロチオン（fenitrothion：MEP）、ホスチアゼート（fosthiazate）、ホルモチオン（formothion）、りん化水素（Hydrogen phosphide）、イソフェンホス（isofenphos）、イソキサチオン（isoxathion）、マラチオン（malathion）、メスルフェンホス（mesulfenfos）、メチダチオン（methidathion：DMTP）、モノクロトホス（monocrotophos）、ナレッド（naled：BRP）、オキシデプロホス（oxydeprofos：ESP）、パラチオン（parathion）、ホサロン（phosalone）、ホスメット（phosmet：PMP）、ピリミホスメチル（pirimiphos-methy1）、ピリダフェンチオン（pyridafenthion）、キナルホス（quinalphos）、フェントエート（phenthoate：PAP）、プロフェノホス（profenofos）、プロパホス（propaphos）、プロチオホス（prothiofos）、ピラクロホス（pyraclorfos）、サリチオン（salithion）、スルプロホス（sulprofos）、テブピリムホス（tebupirimfos）、テメホス（temephos）、テトラクロルビンホス（tetrach1orvinphos）、テルブホス（terbufos）、チオメトン（thiometon）、トリクロルホン（trichlorphon：DEP）、バミドチオン（vamidothion）、フォレート（phorate）、カズサホス（cadusafos）等；
（２）カーバメート系化合物
アラニカルブ（alanycarb）、ベンダイオカルブ（bendiocarb）、ベンフラカルブ（benfuracarb）、BPMC、カルバリル（carbary1）、カルボフラン（carbofuran）、カルボスルファン（carbosulfan）、クロエトカルブ（cloethocarb）、エチオフェンカルブ（ethiofencarb）、フェノブカルブ（fenobucarb）、フェノチオカルブ（fenothiocarb）、フェノキシカルブ（fenoxycarb）、フラチオカルブ（furathiocarb）、イソプロカルブ（isoprocarb：MIPC）、メトルカルブ（metolcarb）、 メソミル（methomyl）、メチオカルブ（methiocarb）、NAC、オキサミル（oxamyl）、ピリミカーブ（pirimicarb）、プロポキスル（propoxur：PHC）、XMC、チオジカルブ（thiodicarb）、 キシリルカルブ（xylylcarb）、アルジカルブ（aldicarb）等；
（３）合成ピレスロイド系化合物
アクリナトリン（acrinathrin）、アレスリン（allethrin）、ベンフルスリン（benfluthrin）、ベータ－シフルトリン（beta-cyfluthrin）、ビフェントリン（bifenthrin）、シクロプロトリン（cycloprothrin）、シフルトリン（cyfluthrin）、シハロトリン（cyhalothrin）、シペルメトリン（cypermethrin）、デルタメトリン（deltamethrin）、エスフェンバレレート（esfenvalerate）、エトフェンプロックス（ethofenprox） 、フェンプロパトリン（fenpropathrin）、フェンバレレート（fenvalerate）、フルシトリネート（flucythrinate）、フルフェンプロックス（flufenoprox）、フルメスリン（flumethrin）、フルバリネート（fluvalinate）、ハルフェンプロックス（halfenprox）、イミプロトリン（imiprothrin）、ペルメトリン（permethrin）、プラレトリン（prallethrin）、ピレトリン（pyrethrins）、レスメトリン（resmethrin）、シグマ－サイパーメスリン（sigma-cypermethrin）、シラフルオフェン（silafluofen）、テフルトリン（tefluthrin）、トラロメトリン（tralomethrin）、トランスフルトリン（transfluthrin）、テトラメトリン（tetramethrin）、フェノトリン（phenothrin）、シフェノトリン（cyphenothrin）、アルファシペルメトリン（alpha-cypermethrin）、ゼータシペルメトリン（zeta-cypermethrin）、ラムダシハロトリン（lambda-cyhalothrin）、フラメトリン（furamethrin）、タウフルバリネート（tau-fluvalinate）、２，３，５，６－テトラフルオロ－4－（メトキシメチル）ベンジル （ＥＺ）－（１ＲＳ，３ＲＳ；１ＲＳ，３ＳＲ）－２，２－ジメチル－3－プロプ－1－エニルシクロプロパンカルボキシレート、２，３，５，６－テトラフルオロ－4－メチルベンジル （ＥＺ）－（１ＲＳ，３ＲＳ；１ＲＳ，３ＳＲ）－２，２－ジメチル－3－プロプ－1－エニルシクロプロパンカルボキシレート、２，３，５，６－テトラフルオロ－4－（メトキシメチル）ベンジル （１ＲＳ，３ＲＳ；１ＲＳ，３ＳＲ）－２，２－ジメチル－3－（２－メチル－１－プロペニル）シクロプロパンカルボキシレート等；
（４）ネライストキシン系化合物
カルタップ（cartap）、ベンスルタップ（bensu1tap）、チオシクラム（thiocyclam）、モノスルタップ（monosultap）、ビスルタップ（bisultap）等；
（５）ネオニコチノイド系化合物
イミダクロプリド（imidac1oprid）、ニテンピラム（nitenpyram）、アセタミプリド（acetamiprid）、チアメトキサム（thiamethoxam）、チアクロプリド（thiacloprid）、ジノテフラン（dinotefuran）、クロチアニジン（clothianidin）等；
（６）ベンゾイル尿素系化合物
クロルフルアズロン（chlorfluazuron）、ビストリフルロン（bistrifluron）、ジアフェンチウロン（diafenthiuron）、ジフルベンズロン（diflubenzuron）、フルアズロン（fluazuron）、フルシクロクスロン（flucycloxuron）、フルフェノクスロン（flufenoxuron）、ヘキサフルムロン（hexaflumuron）、ルフェヌロン（lufenuron）、ノバルロン（novaluron）、ノビフルムロン（noviflumuron）、テフルベンズロン（teflubenzuron）、トリフルムロン（triflumuron）、トリアズロン等；
（７）フェニルピラゾール系化合物
アセトプロール（acetoprole）、エチプロール（ethiprole）、フィプロニル（fiproni1）、バニリプロール（vaniliprole）、ピリプロール（pyriprole）、ピラフルプロール（pyrafluprole）等；
（８）Ｂｔトキシン系殺虫剤
バチルス・チューリンゲンシス菌由来の生芽胞および産生結晶毒素、並びにそれらの混合物；
（９）ヒドラジン系化合物
クロマフェノジド（chromafenozide）、ハロフェノジド（halofenozide）、メトキシフェノジド（methoxyfenozide）、テブフェノジド（tebufenozide）等；
（１０）有機塩素系化合物
アルドリン（aldrin）、ディルドリン（dieldrin）、ジエノクロル（dienochlor）、エンドスルファン（endosulfan）、メトキシクロル（methoxychlor）等；
（１１）天然系殺虫剤
マシン油（machine oil）、硫酸ニコチン（nicotine-sulfate）；
（１２）その他の殺虫剤
アベルメクチン（avermectin-B）、ブロモプロピレート（bromopropylate）、ブプロフェジン（buprofezin）、クロルフェナピル（chlorphenapyr）、シロマジン（cyromazine）、Ｄ－Ｄ（1，3-Dichloropropene）、エマメクチンベンゾエート（emamectin-benzoate）、フェナザキン（fenazaquin）、フルピラゾホス（flupyrazofos）、ハイドロプレン（hydroprene）、メトプレン（methoprene）、インドキサカルブ（indoxacarb）、メトキサジアゾン（metoxadiazone）、ミルベマイシンＡ（milbemycin-A）、ピメトロジン（pymetrozine）、ピリダリル（pyridalyl）、ピリプロキシフェン（pyriproxyfen）、スピノサッド（spinosad）、スルフラミド（sulfluramid）、トルフェンピラド（tolfenpyrad）、トリアゼメイト（triazamate）、フルベンジアミド（flubendiamide）、レピメクチン（lepimectin）、亜ひ酸（Arsenic acid）、ベンクロチアズ（benclothiaz）、石灰窒素（Calcium cyanamide）、石灰硫黄合剤（Calcium polysulfide）、クロルデン（chlordane）、ＤＤＴ、ＤＳＰ、フルフェネリウム（flufenerim）、フロニカミド（flonicamid）、フルリムフェン（flurimfen）、ホルメタネート（formetanate）、メタム・アンモニウム（metam-ammonium）、メタム・ナトリウム（metam-sodium）、臭化メチル（Methyl bromide）、ニディノテフラン（nidinotefuran）、オレイン酸カリウム（Potassium oleate）、プロトリフェンビュート（protrifenbute）、スピロメシフェン（spiromesifen）、硫黄（Sulfur）、メタフルミゾン（metaflumizone）、スピロテトラマット（spirotetramat）、ピリフルキナゾン（pyrifluquinazone）、スピネトラム（spinetoram）、クロラントラニリプロール（chlorantraniliprole）
で示される化合物等が挙げられる。 Examples of such other insecticides include (1) organophosphorus compounds such as acephate, aluminum phosphide, butathiofos, cadusafos, chlorethoxyfos, chlorfenvinphos. (Ch1orfenvinphos), chlorpyrifos (chlorpyrifos), chlorpyrifos-methyl, cyanophos (CYAP), diazinon (diazinon), DCIP (dichlorodiisopropyl ether), dichlorfenthion (ECP), dichlorvos (DDVP), dimethophos (Dimethoate), dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, etrimfos, fenthion (MPP), fenitrothion (MEP), phosti Zeth (fosthiazate), formothion, hydrogen phosphide, isofenphos, isoxathion, malathion, mesulfenfos, methidathion (DMTP), monocrotophos (monocrotophos) , Naled (BRP), oxydeprofos (ESP), parathion, parathion, phosalone, phosmet (PMP), pyrimiphos-methy1, pyridafenthion, quinalphos , Phenthoate (PAP), profenofos, propaphos, prothiofos, pyraclorfos, salithion, sulprofos, tebupirimfos, temephos ), Tetrach1orvinphos, terbufos, thiometon, trichlorphon (DEP), bamidomion, phorate, cadusafos, etc .;
(2) Carbamate compounds alaniccarb, bendiocarb, benfuracarb, BPMC, carbaryl, carbfuran, carbosulfan, cloethocarb, ethiofencarb ), Fenobucarb, fenothiocarb, fenoxycarb, furathiocarb, isoprocarb (MIPC), metolcarb, metomyl, methiocarb, NAC, oxamyl (amyl) ), Pirimicarb, propoxur (PHC), XMC, thiodicarb, xylylcarb, aldicarb, etc .;
(3) Synthetic pyrethroid compounds acrinathrin, allethrin, benfluthrin, beta-cyfluthrin, bifenthrin, cycloprothrin, cyfluthrin, cyhalothrin (cyfluthrin) cyhalothrin), cypermethrin, deltamethrin, esfenvalerate, ethofenprox, fenpropathrin, fenvalerate, flucythrinate, flufenthrinate Prox (flufenoprox), flumethrin, fluvalinate, halfenprox, imiprothrin, permethrin, praretrin, pyre Threin (pyrethrins), resmethrin, sigma-cypermethrin, silafluofen, tefluthrin, tralomethrin, transfluthrin, tetramethrin, othrin Cyphenothrin, alpha-cypermethrin, zeta-cypermethrin, lambda-cyhalothrin, furamethrin, tau-fluvalinate, 2 , 3,5,6-tetrafluoro-4- (methoxymethyl) benzyl (EZ)-(1RS, 3RS; 1RS, 3SR) -2,2-dimethyl-3-prop-1-enylcyclopropanecarboxylate, 2 , 3,5,6-tetrafluoro-4-me Tylbenzyl (EZ)-(1RS, 3RS; 1RS, 3SR) -2,2-dimethyl-3-prop-1-enylcyclopropanecarboxylate, 2,3,5,6-tetrafluoro-4- (methoxymethyl) Benzyl (1RS, 3RS; 1RS, 3SR) -2,2-dimethyl-3- (2-methyl-1-propenyl) cyclopropanecarboxylate and the like;
(4) Nereistoxin compound cartap, bensultap, thiocyclam, monosultap, bisultap, etc .;
(5) neonicotinoid compounds imidacloprid (imidac1oprid), nitenpyram (nitenpyram), acetamiprid (acetamiprid), thiamethoxam (thiamethoxam), thiacloprid, dinotefuran, clothianidin, etc .;
(6) Benzoylurea compounds chlorfluazuron, bistrifluron, diafenthiuron, diflubenzuron, fluazuron, flucycloxuron, flufenoc Flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron, triflumuron, triazuron, etc .;
(7) phenylpyrazole-based compounds acetoprole, ethiprole, fipronil, vaniliprole, pyriprole, pyrafluprole, etc .;
(8) Bt toxin insecticide Bacillus thuringiensis-derived live spores and produced crystal toxins, and mixtures thereof;
(9) Hydrazine-based compounds chromafenozide, halofenozide, methoxyfenozide, tebufenozide and the like;
(10) Organochlorine compounds aldrin, dieldrin, dienochlor, endosulfan, methoxychlor, etc .;
(11) natural insecticide machine oil, nicotine-sulfate;
(12) Other insecticides, avermectin-B, bromopropylate, buprofezin, chlorphenapyr, cyromazine, DD (1,3-Dichloropropene), emamectin benzoate ( emamectin-benzoate, fenazaquin, flupyrazofos, hydroprene, metoprene, indoxacarb, metoxadiazone, milbemycin-A, pymetrozine , Pyridalyl, pyriproxyfen, spinosad, sulfluramid, tolfenpyrad, triazamate, flubendiamide, lepimectin, subpimectin (Arsenic acid), Benclothiaz, Calcium cyanamide, Calcium polysulfide, chlordane, DDT, DSP, flufenerim, flonicamid, flonicamid, flurimfen, formetanate, metam-ammonium, metam-sodium, methyl bromide, nidinotefuran, potassium oleate, prototrifen Bute (protrifenbute), spiromesifen (spiromesifen), sulfur (Sulfur), metaflumizone (metaflumizone), spirotetramat (pyrifluquinazone), spinetoram (spinetoram), chlorantraniliprole (chlorantraniliprole)
And the like.
　かかる他の殺ダニ剤（殺ダニ活性成分）としては、例えばアセキノシル（acequinocyl）、アミトラズ（amitraz）、ベンゾキシメート（benzoximate）、ビフェナゼート（bifenaate）、フェニソブロモレート（bromopropylate）、キノメチオネート（chinomethionat）、クロルベンジレート（chlorobenzilate）、ＣＰＣＢＳ（chlorfenson）、クロフェンテジン（clofentezine）、シフルメトフェン（cyflumetofen）、ケルセン（ジコホル：dicofol）、エトキサゾール（etoxazole）、酸化フェンブタスズ（fenbutatin oxide）、フェノチオカルブ（fenothiocarb）、フェンピロキシメート（fenpyroximate）、フルアクリピリム（fluacrypyrim）、フルプロキシフェン（fluproxyfen）、ヘキシチアゾクス（hexythiazox）、プロパルギット（propargite：BPPS）、ポリナクチン複合体（polynactins）、ピリダベン（pyridaben）、ピリミジフェン（Pyrimidifen）、テブフェンピラド（tebufenpyrad）、テトラジホン（tetradifon）、スピロディクロフェン（spirodiclofen）、スピロメシフェン（spiromesifen）、スピロテトラマット（spirotetramat）、アミドフルメット（amidoflumet）、シエノピラフェン（cyenopyrafen）等が挙げられる。
　かかる他の殺線虫剤（殺線虫活性成分）としては、例えば、ＤＣＩＰ、フォスチアゼート（fosthiazate）、塩酸レバミゾール（levamisol）、メチルイソチオシアネート（methyisothiocyanate）、酒石酸モランテル（morantel tartarate）、イミシアホス（imicyafos）等が挙げられる。 Examples of such other acaricides (acaricidal active ingredients) include, for example, acequinocyl, amitraz, benzoximate, bifenaate, phenisobromolate, quinomethionat , Chlorobenzilate, CPCBS (chlorfenson), clofentezine, cyflumetofen, kelofol, etoxazole, fenbutatin oxide, fenothiocarb, fenpyroxycarb (Fenpyroximate), fluacrypyrim, fluproxyfen, hexythiazox, propargite (BPPS), polynactins, polynactins, pyridaben, Pyrimidifen, tebufenpyrad, tetradifon, spirodiclofen, spiromesifen, spirotetramat, amidoflumet, cyenopyrafen, etc. It is done.
Examples of such other nematicides (nematicidal active ingredients) include, for example, DCIP, fosthiazate, levamisol hydrochloride, methamiisothiocyanate, morantel tartarate, imicyafos Etc.
　本発明防除剤の施用量は、気象条件、製剤形態、施用時期、施用方法、施用場所、対象病害、対象作物等によっても異なるが、本発明防除剤中の本発明化合物量で１０アールあたり、通常１～５００ｇ、好ましくは２～２００ｇである。乳剤、水和剤、懸濁剤等は通常水で希釈して施用されるが、その場合の希釈後の本発明化合物濃度は、通常０．０００５～２重量％、好ましくは０．００５～１重量％であり、粉剤、粒剤等は通常希釈することなくそのまま施用される。種子への処理においては、種子１Ｋｇに対して本発明防除剤中の本発明化合物量で、通常０.００１～１００g、好ましくは０．０１～５０gの範囲で施用される。 The application amount of the present control agent varies depending on weather conditions, formulation form, application time, application method, application location, target disease, target crop, etc., but per 10 ares in terms of the amount of the present compound in the present control agent, Usually, it is 1 to 500 g, preferably 2 to 200 g. Emulsions, wettable powders, suspensions and the like are usually diluted with water and applied. In this case, the concentration of the compound of the present invention after dilution is usually 0.0005 to 2% by weight, preferably 0.005 to 1. The powder, granules and the like are usually applied as they are without dilution. In the seed treatment, the amount of the compound of the present invention in the control agent of the present invention is usually 0.001 to 100 g, preferably 0.01 to 50 g per 1 kg seed.
　本発明防除剤は、畑、水田、芝生、果樹園等の農耕地における植物病害の防除剤として使用することができる。本発明防除剤は、以下に挙げられる「作物」等を栽培する農耕地等において、当該農耕地の病害を防除することができる。 The present control agent can be used as a plant disease control agent in farmland such as fields, paddy fields, lawns, orchards. The control agent of the present invention can control diseases of the farmland in the farmland where the following “crop” and the like are cultivated.
農作物；トウモロコシ、イネ、コムギ、オオムギ、ライムギ、エンバク、ソルガム、ワタ、ダイズ、ピーナッツ、ソバ、テンサイ、ナタネ、ヒマワリ、サトウキビ、タバコ等、野菜；ナス科野菜（ナス、トマト、ピーマン、トウガラシ、ジャガイモ等）、ウリ科野菜（キュウリ、カボチャ、ズッキーニ、スイカ、メロン等）、アブラナ科野菜（ダイコン、カブ、セイヨウワサビ、コールラビ、ハクサイ、キャベツ、カラシナ、ブロッコリー、カリフラワー等）、キク科野菜（ゴボウ、シュンギク、アーティチョーク、レタス等）、ユリ科野菜（ネギ、タマネギ、ニンニク、アスパラガス）、セリ科野菜（ニンジン、パセリ、セロリ、アメリカボウフウ等）、アカザ科野菜（ホウレンソウ、フダンソウ等）、シソ科野菜（シソ、ミント、バジル等）、イチゴ、サツマイモ、ヤマノイモ、サトイモ等、
花卉、
観葉植物、
果樹；仁果類（リンゴ、セイヨウナシ、ニホンナシ、カリン、マルメロ等）、核果類（モモ、スモモ、ネクタリン、ウメ、オウトウ、アンズ、プルーン等）、カンキツ類（ウンシュウミカン、オレンジ、レモン、ライム、グレープフルーツ等）、堅果類（クリ、クルミ、ハシバミ、アーモンド、ピスタチオ、カシューナッツ、マカダミアナッツ等）、液果類（ブルーベリー、クランベリー、ブラックベリー、ラズベリー等）、ブドウ、カキ、オリーブ、ビワ、バナナ、コーヒー、ナツメヤシ、ココヤシ等、
果樹以外の樹；チャ、クワ、花木、街路樹（トネリコ、カバノキ、ハナミズキ、ユーカリ、イチョウ、ライラック、カエデ、カシ、ポプラ、ハナズオウ、フウ、プラタナス、ケヤキ、クロベ、モミノキ、ツガ、ネズ、マツ、トウヒ、イチイ）等。 Agricultural crops: corn, rice, wheat, barley, rye, oats, sorghum, cotton, soybeans, peanuts, buckwheat, sugar beet, rapeseed, sunflower, sugarcane, tobacco, vegetables, solanaceous vegetables (eggplants, tomatoes, peppers, peppers, potatoes) Cucumber, pumpkin, zucchini, watermelon, melon, etc., cruciferous vegetables (radish, turnip, horseradish, kohlrabi, cabbage, cabbage, mustard, broccoli, cauliflower, etc.), asteraceae (burdock, Shungiku, artichokes, lettuce, etc.), liliaceae vegetables (leek, onion, garlic, asparagus), celeryaceae vegetables (carrot, parsley, celery, red pepper, etc.), red crustacean vegetables (spinach, chard, etc.) (Perilla, mint, basil ), Strawberry, sweet potato, yam, taro, etc.,
Bridegroom,
Foliage plant,
Fruit trees; pears (apples, pears, Japanese pears, quince, quince, etc.), nuclear fruits (peaches, plums, nectarines, ume, sweet cherry, apricots, prunes, etc.), citrus (satsuma mandarin, orange, lemon, lime, grapefruit) ), Nuts (chestnut, walnut, hazel, almond, pistachio, cashew nut, macadamia nut, etc.), berries (blueberry, cranberry, blackberry, raspberry, etc.), grape, oyster, olive, loquat, banana, coffee, Date palm, coconut palm, etc.
Trees other than fruit trees: Cha, mulberry, flowering trees, street trees (ash, birch, dogwood, eucalyptus, ginkgo, lilac, maple, oak, poplar, redwood, fu, sycamore, zelkova, black bean, peach tree, Tsuga, rat, pine, Spruce, yew) etc.
　上記「作物」とは、イソキサフルトール等のHPPD阻害剤、イマゼタピル、チフェンスルフロンメチル等のALS阻害剤、EPSP合成酵素阻害剤、グルタミン合成酵素阻害剤、ブロモキシニル等の除草剤に対する耐性が、古典的な育種法、もしくは遺伝子組換え技術により付与された作物も含まれる。 The above-mentioned `` crop '' is resistant to HPPD inhibitors such as isoxaflutole, ALS inhibitors such as imazetapyr and thifensulfuron methyl, EPSP synthase inhibitors, glutamine synthase inhibitors, herbicides such as bromoxynil, This includes crops granted by classical breeding methods or genetic engineering techniques.
　古典的な育種法により耐性が付与された「作物」の例として、イマゼタピル等のイミダゾリノン系除草剤耐性のClearfield（登録商標）カノーラ、チフェンスルフロンメチル等のスルホニルウレア系ALS阻害型除草剤耐性のSTSダイズ等がある。また、遺伝子組換え技術により耐性が付与された「作物」の例として、グリホサートやグルホシネート耐性のトウモロコシ品種があり、RoundupReady（登録商標）及びLibertyLink（登録商標）等の商品名ですでに販売されている。 As an example of a “crop” to which resistance has been imparted by a classic breeding method, imidazolinone herbicide-resistant Clearfield (registered trademark) canola, such as imazetapil, and sulfonylurea-based ALS-inhibiting herbicide resistance such as thifensulfuron methyl There are STS soybeans. In addition, examples of “crop” to which tolerance has been imparted by genetic engineering techniques include glyphosate and glufosinate-resistant corn varieties that have already been sold under trade names such as RoundupReady (registered trademark) and LibertyLink (registered trademark). Yes.
　上記「作物」とは、遺伝子組換え技術を用いて、例えば、バチルス属で知られている選択的毒素等を合成する事が可能となった作物も含まれる。
　この様な遺伝子組換え植物で発現される毒素として、バチルス・セレウスやバチルス・ポピリエ由来の殺虫性タンパク；バチルス・チューリンゲンシス由来のCry1Ab、Cry1Ac、Cry1F、Cry1Fa2、Cry2Ab、Cry3A、Cry3Bb1またはCry9C等のδ－エンドトキシン、VIP1、VIP2、VIP3またはVIP3A等の殺虫タンパク；線虫由来の殺虫タンパク；さそり毒素、クモ毒素、ハチ毒素または昆虫特異的神経毒素等動物によって産生される毒素；糸状菌類毒素；植物レクチン；アグルチニン；トリプシン阻害剤、セリンプロテアーゼ阻害剤、パタチン、シスタチン、パパイン阻害剤等のプロテアーゼ阻害剤；リシン、トウモロコシ－RIP、アブリン、ルフィン、サポリン、ブリオジン等のリボゾーム不活性化タンパク（RIP）；３－ヒドロキシステロイドオキシダーゼ、エクジステロイド－UDP－グルコシルトランスフェラーゼ、コレステロールオキシダーゼ等のステロイド代謝酵素；エクダイソン阻害剤；HMG-COAリダクターゼ；ナトリウムチャネル、カルシウムチャネル阻害剤等のイオンチャネル阻害剤；幼若ホルモンエステラーゼ；利尿ホルモン受容体；スチルベンシンターゼ；ビベンジルシンターゼ；キチナーゼ；グルカナーゼ等が挙げられる。 The above “crop” includes, for example, crops that can synthesize selective toxins known in the genus Bacillus using genetic recombination techniques.
Toxins expressed in such genetically modified plants include insecticidal proteins from Bacillus cereus and Bacillus popirie; Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, Cry3Bb1 or Cry9C from Bacillus thuringiensis Insecticidal proteins such as δ-endotoxin, VIP1, VIP2, VIP3 or VIP3A; nematode-derived insecticidal proteins; toxins produced by animals such as scorpion toxins, spider toxins, bee toxins or insect-specific neurotoxins; filamentous fungal toxins; plants Lectin; agglutinin; protease inhibitors such as trypsin inhibitor, serine protease inhibitor, patatin, cystatin, papain inhibitor; ribosome inactivating protein (RIP) such as lysine, corn-RIP, abrin, ruffin, saporin, bryodin; 3-hydroxysteroid oxidase, ecdysteroid Steroid metabolic enzymes such as UDP-glucosyltransferase and cholesterol oxidase; ecdysone inhibitor; HMG-COA reductase; ion channel inhibitors such as sodium channel and calcium channel inhibitor; juvenile hormone esterase; diuretic hormone receptor; stilbene synthase; Benzyl synthase; chitinase; glucanase and the like.
　またこの様な遺伝子組換え作物で発現される毒素として、Cry1Ab、Cry1Ac、Cry1F、Cry1Fa2、Cry2Ab、Cry3A、Cry3Bb1又はCry9C等のδ－エンドトキシンタンパク、VIP1、VIP2、VIP3またはVIP3A等の殺虫タンパクのハイブリッド毒素、一部を欠損した毒素、修飾された毒素も含まれる。ハイブリッド毒素は組換え技術を用いて、これらタンパクの異なるドメインの新しい組み合わせによって作り出される。一部を欠損した毒素としては、アミノ酸配列の一部を欠損したCry1Abが知られている。修飾された毒素としては、天然型の毒素のアミノ酸の1つ又は複数が置換されている。
　これら毒素の例及びこれら毒素を合成する事ができる組換え植物は、EP-A-0 374 753、WO 93/07278、WO 95/34656、EP-A-0 427 529、EP-A-451 878、WO 03/052073等に記載されている。
　これらの組換え植物に含まれる毒素は、特に、甲虫目害虫、双翅目害虫、鱗翅目害虫への耐性を植物へ付与する。 Also, toxins expressed in such genetically modified crops include Cry1Ab, Cry1Ac, Cry1F, Cry1Fa2, Cry2Ab, Cry3A, δ-endotoxin proteins such as Cry3Bb1 or Cry9C, and insecticidal protein hybrids such as VIP1, VIP2, VIP3 or VIP3A Toxins, partially defective toxins, modified toxins are also included. Hybrid toxins are produced by new combinations of different domains of these proteins using recombinant techniques. As a toxin lacking a part, Cry1Ab lacking a part of the amino acid sequence is known. In the modified toxin, one or more amino acids of the natural toxin are substituted.
Examples of these toxins and recombinant plants capable of synthesizing these toxins are EP-A-0 374 753, WO 93/07278, WO 95/34656, EP-A-0 427 529, EP-A-451 878. , WO 03/052073 and the like.
The toxins contained in these recombinant plants particularly confer resistance to Coleoptera pests, Diptera pests, and Lepidoptera pests.
　また、1つ若しくは複数の殺虫性の害虫抵抗性遺伝子を含み、1つ又は複数の毒素を発現する遺伝子組換え植物は既に知られており、いくつかのものは市販されている。これら遺伝子組換え植物の例として、YieldGard（登録商標）（Cry1Ab毒素を発現するトウモロコシ品種）、YieldGard Rootworm（登録商標）（Cry3Bb1毒素を発現するトウモロコシ品種）、YieldGard Plus（登録商標）（Cry1AbとCry3Bb1毒素を発現するトウモロコシ品種）、Herculex I（登録商標）（Cry1Fa2毒素とグルホシネートへの耐性を付与する為にホスフィノトリシン Ｎ－アサチルトランスフェラーゼ（PAT）を発現するトウモロコシ品種）、NuCOTN33B（Cry1Ac毒素を発現するワタ品種）、Bollgard I（登録商標）（Cry1Ac毒素を発現するワタ品種）、Bollgard II（登録商標）（Cry1AcとCry2Ab毒素とを発現するワタ品種）、VIPCOT（登録商標）（VIP毒素を発現するワタ品種）、NewLeaf（登録商標）（Cry3A毒素を発現するジャガイモ品種）、NatureGard（登録商標）Agrisure（登録商標）GT Advantage（GA21 グリホサート耐性形質）、Agrisure（登録商標） CB Advantage（Bt11コーンボーラー（CB）形質）、Protecta（登録商標）等が挙げられる。 Also, genetically modified plants that contain one or more insecticidal pest resistance genes and express one or more toxins are already known, and some are commercially available. Examples of these transgenic plants include YieldGard® (a corn variety expressing Cry1Ab toxin), YieldGardGRootworm® (a corn variety expressing Cry3Bb1 toxin), YieldGard Plus® (Cry1Ab and Cry3Bb1) Corn varieties that express toxins), Herculex I® (corn varieties that express phosphinotricin N-assyltransferase (PAT) to confer resistance to Cry1Fa2 toxin and glufosinate), NuCOTN33B (Cry1Ac toxin) Cotton varieties expressing), Bollgard I (registered trademark) (cotton varieties expressing Cry1Ac toxin), Bollgard II (registered trademark) (cotton varieties expressing Cry1Ac and Cry2Ab toxin), VIPCOT (registered trademark) (VIP toxin) Cotton varieties), NewLeaf (registered trademark) (potato varieties expressing Cry3A toxin), NatureGard (registered trademark) Agrisure (registered trademark) GT Advantage (GA21 glyphosate-tolerant trait), Agrisure (registered trademark) CB Advantage (Bt11 corn borer (CB) character), Protecta (registered trademark).
　上記「作物」とは、遺伝子組換え技術を用いて、選択的な作用を有する抗病原性物質を産生する能力を付与されたものも含まれる。
　抗病原性物質の例として、PRタンパク等が知られている（PRPs、EP-A-0 392 225）。このような抗病原性物質とそれを産生する遺伝子組換え植物は、EP-A-0 392 225、WO 95/33818、EP-A-0 353 191等に記載されている。
　こうした遺伝子組換え植物で発現される抗病原性物質の例として、例えば、ナトリウムチャネル阻害剤、カルシウムチャネル阻害剤（ウイルスが産生するKP1、KP4、KP6毒素等が知られている。）等のイオンチャネル阻害剤；スチルベンシンターゼ；ビベンジルシンターゼ；キチナーゼ；グルカナーゼ；PRタンパク；ペプチド抗生物質、ヘテロ環を有する抗生物質、植物病害抵抗性に関与するタンパク因子（植物病害抵抗性遺伝子と呼ばれ、WO 03/000906に記載されている。）等の微生物が産生する抗病原性物質等が挙げられる。 The above “crop” includes those given the ability to produce an anti-pathogenic substance having a selective action using genetic recombination technology.
PR proteins and the like are known as examples of anti-pathogenic substances (PRPs, EP-A-0 392 225). Such anti-pathogenic substances and genetically modified plants that produce them are described in EP-A-0 392 225, WO 95/33818, EP-A-0 353 191 and the like.
Examples of anti-pathogenic substances expressed in such genetically modified plants include, for example, sodium channel inhibitors, calcium channel inhibitors (KP1, KP4, KP6 toxins produced by viruses, etc.) and the like. Ion channel inhibitors; stilbene synthase; bibenzyl synthase; chitinase; glucanase; PR protein; peptide antibiotics, heterocyclic antibiotics, protein factors involved in plant disease resistance 03/000906)) and other anti-pathogenic substances produced by microorganisms.
　本発明により防除することができる植物病害としては、例えば糸状菌等が挙げられ、より詳しくは以下の病害を挙げることができるが、これらに限定されるものではない。
　通常、本発明防除方法は、本発明防除剤を前記した本発明防除剤を施用する方法で用いることにより行われる。 Examples of plant diseases that can be controlled by the present invention include filamentous fungi and the like, and more specifically, the following diseases can be mentioned, but are not limited thereto.
Usually, this invention control method is performed by using this invention control agent by the method of applying this invention control agent mentioned above.
イネのいもち病（Magnaporthe grisea）、ごま葉枯病（Cochliobolus miyabeanus）、紋枯病（Rhizoctonia solani）、馬鹿苗病（Gibberella fujikuroi）、黄化萎縮病（Sclerophthora macrospora）；ムギ類のうどんこ病（Erysiphe graminis）、赤かび病（Fusarium graminearum, F. avenacerum, F. culmorum, Microdochium nivale）、さび病（Puccinia striiformis， P. graminis, P. recondita, P. hordei）、雪腐病（Typhula sp.,Micronectriella nivalis）、裸黒穂病（Ustilago tritici, U. nuda）、なまぐさ黒穂病（Tilletia caries）、眼紋病（Pseudocercosporella herpotrichoides）、雲形病（Rhynchosporium secalis）、葉枯病（Septoria tritici）、ふ枯病（Leptosphaeria nodorum）、網斑病（Pyrenophora teres Drechsler）、立枯病（Gaeumannomyces graminis）、黄斑病（Pyrenophora tritici-repentis）；カンキツ類の黒点病（Diaporthe citri）、そうか病（Elsinoe fawcetti）、果実腐敗病（Penicillium digitatum, P. italicum）；リンゴのモニリア病（Monilinia mali）、腐らん病（Valsa ceratosperma）、うどんこ病（Podosphaera leucotricha）、斑点落葉病（Alternaria alternata apple pathotype）、黒星病（Venturia inaequalis）、炭そ病（Glomerella cingulata）；ナシの黒星病（Venturia nashicola, V. pirina）、黒斑病（Alternaria alternata Japanese pear pathotype）、赤星病（Gymnosporangium haraeanum）；モモの灰星病（Monilinia fructicola）、黒星病（Cladosporium carpophilum）、フォモプシス腐敗病（Phomopsis sp.）；ブドウの黒とう病（Elsinoe ampelina）、晩腐病（Glomerella cingulata）、うどんこ病（Uncinula necator）、さび病（Phakopsora ampelopsidis）、ブラックロット病（Guignardia bidwellii）、べと病（Plasmopara viticola）；カキの炭そ病（Gloeosporium kaki）、落葉病（Cercospora kaki, Mycosphaerella nawae）；ウリ類の炭そ病（Colletotrichum lagenarium）、うどんこ病（Sphaerotheca fuliginea）、つる枯病（Mycosphaerella melonis）、つる割病（Fusarium oxysporum）、べと病（Pseudoperonospora cubensis）、疫病（Phytophthora sp.）、苗立枯病（Pythium sp.）；トマトの輪紋病（Alternaria solani）、葉かび病（Cladosporium fulvum）、疫病（Phytophthora infestans）；ナスの褐紋病（Phomopsis vexans）、うどんこ病（Erysiphe cichoracearum）；アブラナ科野菜の黒斑病（Alternaria japonica）、白斑病（Cercosporella brassicae）、根こぶ病（Plasmodiophora parasitica）、べと病（Peronospora parasitica）；ネギのさび病（Puccinia allii）、ダイズの紫斑病（Cercospora kikuchii）、黒とう病（Elsinoe glycines）、黒点病（Diaporthe phaseolorum var. sojae）、さび病( Phakopsora pachyrhizi)、インゲンの炭そ病（Colletotrichum lindemthianum）ラッカセイの黒渋病（Cercospora personata）、褐斑病（Cercospora arachidicola）、白絹病（Sclerotium rolfsii）；エンドウのうどんこ病（Erysiphe pisi）；ジャガイモの夏疫病（Alternaria solani）、疫病（Phytophthora infestans）、半身萎凋病（Verticillium albo-atrum, V. dahliae, V. nigrescens）；イチゴのうどんこ病（Sphaerotheca humuli）；チャの網もち病（Exobasidium reticulatum）；白星病（Elsinoe leucospila）、輪斑病（Pestalotiopsis sp.）、炭そ病（Colletotrichum theae-sinensis）タバコの赤星病（Alternaria longipes）、うどんこ病（Erysiphe cichoracearum）、炭そ病（Colletotrichum tabacum）、べと病（Peronospora tabacina）、疫病（Phytophthora nicotianae）；テンサイの褐斑病（Cercospora beticola）、葉腐病（Thanatephorus cucumeris）、根腐病（Thanatephorus cucumeris）、黒根病（Aphanomyces sochlioides）；バラの黒星病（Diplocarpon rosae）、うどんこ病（Sphaerotheca pannosa）；キクの褐斑病（Septoria chrysanthemi－indici）、白さび病（Puccinia horiana）；タマネギの白斑葉枯病(Botrytis cinerea, B. byssoidea, B. squamosa)、灰色腐敗病（Botrytis alli）；小菌核性腐敗病（Botrytis squamosa）種々の作物の灰色かび病（Botrytis cinerea）、菌核病（Sclerotinia sclerotiorum）；ダイコン黒斑病（（Alternaria brassicicola）；シバのダラースポット病（Sclerotinia homeocarpa）、シバのブラウンパッチ病およびラージパッチ病（Rhizoctonia solani）；並びにバナナのシガトカ病（Mycosphaerella fijiensis、Mycosphaerella musicola）。 Rice blast (Magnaporthe grisea), sesame leaf blight (Cochliobolus miyabeanus), blight (Rhizoctonia solani), idiot seedling (Gibberella fujikuroi), yellow dwarf disease (Sclerophthora macrospora); wheat powdery mildew (Sclerophthora macrospora) Erysiphe graminis), red mold disease (Fusarium graminearum, F. avenacerum, F. culmorum, Microdochium nivale), rust disease (Puccinia striiformis, P. graminis, P. recondita, P. hordei), snow rot (Typh) Micronectriella nivalis), Bare Scarlet (Ustilago tritici, U. nuda), Namagusa Scab (Tilletia caries), Eyelid (Pseudocercosporella herpotrichoides), Cloudy (Rhynchosporium secalis), Leaf Blight (Septoria tritic) (Leptosphaeria nodorum), net blotch disease (Pyrenophora teres Drechsler), blight (Gaeumannomyces graminis), yellow spot disease (Pyrenophora tritici-repentis); citrus black spot disease (Diaporthe citri), scab (Elsinoe fawcet) i), fruit rot (Penicillium digitatum, P. italicum); apple monilia disease (Monilinia mali), rot (Valsa ceratosperma), powdery mildew (Podosphaera leucotricha), spotted leaf disease (Alternaria alternata apple pathotype), black star Disease (Venturia inaequalis), anthracnose (Glomerella cingulata); pear black spot disease (Venturia nashicola, V. pirina), black spot disease (Alternaria alternata Japanese pear pathotype), red star disease (Gymnosporangium haraeanum); (Monilinia fructicola), black scab (Cladosporium carpophilum), fomopsis rot (Phomopsis sp.); Grape black rot (Elsinoe ampelina), late rot (Glomerella cingulata), powdery mildew (Uncinula necator), rust ( Phakopsora ampelopsidis), Blacklot's disease (Guignardia bidwellii), downy mildew (Plasmopara viticola); osphaerella nawae); cucurbit (Colletotrichum lagenarium), powdery mildew (Sphaerotheca fuliginea), vine blight (Mycosphaerella melonis), vine split disease (Fusarium 割 oxysporum), downy mildew (Pseudoperonospora cubenhy), plague sp.), seedling blight (Pythium sp.); tomato ringworm (Alternaria solani), leaf mold (Cladosporium fulvum), plague (Phytophthora infestans); eggplant brown coat (Phomopsis 紋 vexans), powdery mildew Disease (Erysiphe cichoracearum); Brassica black spot (Alternaria japonica), Vitiligo (Cercosporella brassicae), Clubroot (Plasmodiophora parasitica), Downy mildew (Peronospora parasitica); Green onion rust (Puccinia allii) Soybean purpura (Cercospora kikuchii), black scab (Elsinoe glycines), black spot (Diaporthe phaseolorum var. Sojae), rust (Phakopsora pachyrhizi), bean anthracnose (Colletotrichum linde) mthianum) groundnut black rot (Cercospora personata), brown spot (Cercospora arachidicola), white silkworm (Sclerotium rolfsii); pea powdery mildew (Erysiphe pisi); potato summer plague (Alternaria solani), plague (Phytophthora) infestans), half body wilt disease (Verticillium albo-atrum, V.ahdahliae, V. nigrescens); Strawberry powdery mildew (Sphaerotheca humuli); Cha net rot (Exobasidium reticulatum); White star disease (Elsinoe leucospila) Disease (Pestalotiopsis sp.), Anthracnose (Colletotrichum theae-sinensis) Tobacco Red Star Disease (Alternaria longipes), Powdery Mildew (Erysiphe cichoracearum), Anthracnose (Colletotrichum tabacum), Downy mildew (Peronospora tabacina), Epidemic (Phytophthora nicotianae); brown spot of sugar beet (Cercospora beticola), leaf rot (Thanatephorus cucumeris), root rot (Thanatephorus cucumeris), black root disease (Aphanomyces sochlioides); Black spot disease (Diplocarpon rosae), powdery mildew (Sphaerotheca pannosa); chrysanthemum leaf spot (Septoria chrysanthemi-indici), white rust (Puccinia horiana); onion leaf spot (Botrytis cinerea, reaB. Byssoidea, B. squamosa), gray rot (Botrytis alli); small rot rot (Botrytisasquamosa) gray fungus of various crops (Botrytis） cinerea), sclerotia (Sclerotinia sclerotiorum); radish black spot (Alternaria) brassicicola); Shirah's dollar spot disease (Sclerotinia homeocarpa), Shiva's brown patch disease and large patch disease (Rhizoctonia solani); and Banana's Sigatoka disease (Mycosphaerella fijiensis, Mycosphaerella musicola).
　以下、本発明を製造例、製剤例及び試験例等を示す。 Hereinafter, the present invention will be shown in production examples, formulation examples, test examples, and the like.
製造例１
　２－フルオロ－３－メトキシアニリン０．２０ｇ、キノリン－６－カルボン酸０．３ｇ、ＷＳＣ０．４０ｇ、ピリジン０．５ｍｌ及びＤＭＦ５ｍｌの混合物を室温で５時間撹拌した。その後、反応混合物に水を加え酢酸エチルで抽出した。有機層を飽和食塩水で洗浄後、硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２’－フルオロ－３’－メトキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物１と記す。）０．２９ｇを得た。
本発明化合物１
Figure JPOXMLDOC01-appb-C000011
 1H-NMR (CDCl3) δ: 3.93 (3H, s), 6.80 (1H, td, J = 8.3, 1.5 Hz), 7.14 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.1 Hz), 8.08-8.12 (1H, m), 8.18 (1H, dd, J = 8.8, 2.0 Hz), 8.21 (1H, s), 8.24 (1H, d, J = 8.8 Hz), 8.31 (1H, dd, J = 8.4, 1.1 Hz), 8.42 (1H, d, J = 2.0 Hz), 9.04 (1H, dd, J = 4.1, 1.7 Hz). Production Example 1
A mixture of 0.20 g of 2-fluoro-3-methoxyaniline, 0.3 g of quinoline-6-carboxylic acid, 0.40 g of WSC, 0.5 ml of pyridine and 5 ml of DMF was stirred at room temperature for 5 hours. Thereafter, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 0.29 g of 2′-fluoro-3′-methoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 1).
Compound 1 of the present invention
Figure JPOXMLDOC01-appb-C000011
 1 H-NMR (CDCl 3 ) δ: 3.93 (3H, s), 6.80 (1H, td, J = 8.3, 1.5 Hz), 7.14 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd , J = 8.3, 4.1 Hz), 8.08-8.12 (1H, m), 8.18 (1H, dd, J = 8.8, 2.0 Hz), 8.21 (1H, s), 8.24 (1H, d, J = 8.8 Hz) , 8.31 (1H, dd, J = 8.4, 1.1 Hz), 8.42 (1H, d, J = 2.0 Hz), 9.04 (1H, dd, J = 4.1, 1.7 Hz).
製造例２
　キノリン－６－カルボン酸０．３５ｇ、３－フェノキシアニリン０．３７ｇ及びＤＭＦ５ｍｌの混合物に、ＢＯＰ試薬０．８８ｇ及びトリエチルアミン０．４０ｇを順次加えて、室温で４時間攪拌した。反応混合物に氷及び水４０ｍｌを順次加え、室温で３０分間、次いで氷冷下で３０分間攪拌した。生じた固体をろ過により集め、水及び冷ＭＴＢＥで順次洗浄した後、乾燥させて、３’－ フェノキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物２と記す。）０．５７ｇを得た。
　本発明化合物２
Figure JPOXMLDOC01-appb-C000012
 1H-NMR (CDCl3) δ:  6.82-6.85 (1H, m), 7.05-7.07 (2H, m), 7.11-7.15 (1H, m), 7.32-7.38 (4H, m), 7.44-7.51 (2H, m), 8.05 (1H, br s), 8.11 (1H, dd, J = 8.8, 1.7 Hz), 8.18 (1H, d, J = 8.8 Hz), 8.24 (1H, d, J = 7.8 Hz), 8.36 (1H, d, J = 1.7 Hz), 9.00 (1H, dd, J = 4.1, 1.7 Hz). Production Example 2
To a mixture of 0.35 g of quinoline-6-carboxylic acid, 0.37 g of 3-phenoxyaniline, and 5 ml of DMF, 0.88 g of BOP reagent and 0.40 g of triethylamine were sequentially added, followed by stirring at room temperature for 4 hours. Ice and 40 ml of water were sequentially added to the reaction mixture, and the mixture was stirred at room temperature for 30 minutes and then under ice-cooling for 30 minutes. The resulting solid was collected by filtration, washed successively with water and cold MTBE, and then dried to obtain 0.57 g of 3′-phenoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 2). It was.
Compound 2 of the present invention
Figure JPOXMLDOC01-appb-C000012
 1 H-NMR (CDCl 3 ) δ: 6.82-6.85 (1H, m), 7.05-7.07 (2H, m), 7.11-7.15 (1H, m), 7.32-7.38 (4H, m), 7.44-7.51 ( 2H, m), 8.05 (1H, br s), 8.11 (1H, dd, J = 8.8, 1.7 Hz), 8.18 (1H, d, J = 8.8 Hz), 8.24 (1H, d, J = 7.8 Hz) , 8.36 (1H, d, J = 1.7 Hz), 9.00 (1H, dd, J = 4.1, 1.7 Hz).
製造例３
　キノリン－６－カルボン酸０．３５ｇ、３－メトキシアニリン０．２５ｇ及びＤＭＦ５ｍｌの混合物に、ＢＯＰ試薬０．８８ｇ及びトリエチルアミン０．４０ｇを順次加えて、室温で４時間攪拌した。反応混合物に氷及び水４０ｍｌを順次加え、室温で３０分間、次いで氷冷下で３０分間攪拌した。一晩放置して生じた固体をろ過により集め、水及び冷ＭＴＢＥで順次洗浄した後、乾燥させて、３’－ メトキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物３と記す。）０．５７ｇを得た。
　本発明化合物３
Figure JPOXMLDOC01-appb-C000013
 1H-NMR (CDCl3) δ: 3.86 (3H, s), 6.74-6.76 (1H, m), 7.15-7.17 (1H, m), 7.28-7.32 (1H, m), 7.47-7.52 (2H, m), 8.00 (1H, br s), 8.14 (1H, dd, J = 8.8, 2.0 Hz), 8.22 (1H, d, J = 8.8 Hz), 8.28 (1H, d, J = 7.6 Hz), 8.40 (1H, d, J = 2.0 Hz), 9.01 (1H, dd, J = 4.1, 1.7 Hz). Production Example 3
To a mixture of 0.35 g of quinoline-6-carboxylic acid, 0.25 g of 3-methoxyaniline, and 5 ml of DMF, 0.88 g of BOP reagent and 0.40 g of triethylamine were sequentially added and stirred at room temperature for 4 hours. Ice and 40 ml of water were sequentially added to the reaction mixture, and the mixture was stirred at room temperature for 30 minutes and then under ice-cooling for 30 minutes. The solid that was left overnight was collected by filtration, washed successively with water and cold MTBE, then dried and 3′-methoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 3). 0.57 g was obtained.
Compound 3 of the present invention
Figure JPOXMLDOC01-appb-C000013
 1 H-NMR (CDCl 3 ) δ: 3.86 (3H, s), 6.74-6.76 (1H, m), 7.15-7.17 (1H, m), 7.28-7.32 (1H, m), 7.47-7.52 (2H, m), 8.00 (1H, br s), 8.14 (1H, dd, J = 8.8, 2.0 Hz), 8.22 (1H, d, J = 8.8 Hz), 8.28 (1H, d, J = 7.6 Hz), 8.40 (1H, d, J = 2.0 Hz), 9.01 (1H, dd, J = 4.1, 1.7 Hz).
製造例４
　キノリン－６－カルボン酸０．３５ｇ、３－エトキシアニリン０．２７ｇ及びＤＭＦ５ｍｌの混合物にＢＯＰ試薬０．８８ｇ及びトリエチルアミン０．４０ｇを順次加えて、室温で４時間攪拌した。反応混合物に氷及び水４０ｍｌを順次加え、室温で３０分間、次いで氷冷下で３０分間攪拌した。一晩放置して生じた固体をろ過により集め、水及び冷ＭＴＢＥで順次洗浄した後、乾燥させて、３’－エトキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物４と記す。）０．６０ｇを得た。
　本発明化合物４
Figure JPOXMLDOC01-appb-C000014
 1H-NMR (CDCl3) δ: 1.43 (3H, t, J = 7.1 Hz), 4.08 (2H, q, J = 7.1 Hz), 6.72-6.74 (1H, m), 7.15-7.17 (1H, m), 7.28-7.30 (1H, m), 7.47-7.52 (2H, m), 8.01 (1H, br s), 8.12-8.15 (1H, m), 8.21 (1H, d, J = 9.0 Hz), 8.27 (1H, d, J = 7.8 Hz), 8.40 (1H, d, J = 1.7 Hz), 9.01-9.02 (1H, m). Production Example 4
To a mixture of 0.35 g of quinoline-6-carboxylic acid, 0.27 g of 3-ethoxyaniline and 5 ml of DMF, 0.88 g of BOP reagent and 0.40 g of triethylamine were sequentially added, followed by stirring at room temperature for 4 hours. Ice and 40 ml of water were sequentially added to the reaction mixture, and the mixture was stirred at room temperature for 30 minutes and then under ice-cooling for 30 minutes. The solid that was allowed to stand overnight was collected by filtration, washed successively with water and cold MTBE, then dried and 3′-ethoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as Compound 4 of the present invention). 0.60 g was obtained.
Compound 4 of the present invention
Figure JPOXMLDOC01-appb-C000014
 1 H-NMR (CDCl 3 ) δ: 1.43 (3H, t, J = 7.1 Hz), 4.08 (2H, q, J = 7.1 Hz), 6.72-6.74 (1H, m), 7.15-7.17 (1H, m ), 7.28-7.30 (1H, m), 7.47-7.52 (2H, m), 8.01 (1H, br s), 8.12-8.15 (1H, m), 8.21 (1H, d, J = 9.0 Hz), 8.27 (1H, d, J = 7.8 Hz), 8.40 (1H, d, J = 1.7 Hz), 9.01-9.02 (1H, m).
製造例５
　キノリン－６－カルボン酸３４６ｍｇ、４－メチルアニリン２１４ｍｇ、ＷＳＣ５７５ｍｇ、１－ヒドロキシベンゾトリアゾール２７０ｍｇ及びトリエチルアミン０．２８ｍｌをＤＭＦ２．３ｍｌに加え、１００℃で４時間攪拌した。室温付近まで放冷した反応混合物に飽和食塩水を加え、酢酸エチルで抽出した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して４’－メチル－キノリン－６－カルボン酸アニリド（以下、本発明化合物５と記す。）２８５ｍｇを得た。
　本発明化合物５
Figure JPOXMLDOC01-appb-C000015
 1H-NMR (CDCl3) δ: 2.36 (3H, s), 7.20 (2H, d, J = 8.3 Hz), 7.49 (1H, dd, J = 8.2, 4.3 Hz), 7.57 (2H, d, J = 8.3 Hz), 7.97 (1H, br s), 8.14 (1H, dd, J = 8.8, 1.8 Hz), 8.20 (1H, d, J = 8.8 Hz), 8.26 (1H, dd, J = 8.3, 1.0 Hz), 8.39 (1H, d, J = 1.8 Hz), 9.01 (1H, dd, J = 4.3, 1.8 Hz). Production Example 5
Quinoline-6-carboxylic acid (346 mg), 4-methylaniline (214 mg), WSC (575 mg), 1-hydroxybenzotriazole (270 mg) and triethylamine (0.28 ml) were added to DMF (2.3 ml), and the mixture was stirred at 100 ° C. for 4 hours. Saturated brine was added to the reaction mixture which had been allowed to cool to near room temperature, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 285 mg of 4′-methyl-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 5).
Compound 5 of the present invention
Figure JPOXMLDOC01-appb-C000015
 1 H-NMR (CDCl 3 ) δ: 2.36 (3H, s), 7.20 (2H, d, J = 8.3 Hz), 7.49 (1H, dd, J = 8.2, 4.3 Hz), 7.57 (2H, d, J = 8.3 Hz), 7.97 (1H, br s), 8.14 (1H, dd, J = 8.8, 1.8 Hz), 8.20 (1H, d, J = 8.8 Hz), 8.26 (1H, dd, J = 8.3, 1.0 Hz), 8.39 (1H, d, J = 1.8 Hz), 9.01 (1H, dd, J = 4.3, 1.8 Hz).
製造例６
　キノリン－６－カルボン酸３４６ｍｇ、３－メチルアニリン２１４ｍｇ、ＷＳＣ５７５ｍｇ、１－ヒドロキシベンゾトリアゾール２７０ｍｇ及びトリエチルアミン０．２８ｍｌをＤＭＦ２．１ｍｌに加え、１００℃で４時間攪拌した。室温付近まで放冷した反応混合物に飽和食塩水を加え、酢酸エチルで抽出した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して３’－メチル－キノリン－６－カルボン酸アニリド（以下、本発明化合物６と記す。）２５２ｍｇを得た。
　本発明化合物６
Figure JPOXMLDOC01-appb-C000016
 1H -NMR (CDCl3) δ: 2.39 (3H, s), 7.00 (1H, d, J = 7.6 Hz), 7.29 (1H, d, J = 7.8 Hz), 7.46-7.51 (2H, m), 7.55 (1H, s), 8.00 (1H, br s), 8.13 (1H, dd, J = 8.8, 2.0 Hz), 8.20 (1H, d, J = 8.8 Hz), 8.26 (1H, dd, J = 8.3, 1.3 Hz), 8.38 (1H, d, J = 2.0 Hz), 9.01 (1H, dd, J = 4.2, 1.6 Hz). Production Example 6
Quinoline-6-carboxylic acid (346 mg), 3-methylaniline (214 mg), WSC (575 mg), 1-hydroxybenzotriazole (270 mg) and triethylamine (0.28 ml) were added to DMF (2.1 ml), and the mixture was stirred at 100 ° C. for 4 hours. Saturated brine was added to the reaction mixture which had been allowed to cool to near room temperature, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 252 mg of 3′-methyl-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 6).
Compound 6 of the present invention
Figure JPOXMLDOC01-appb-C000016
 1 H -NMR (CDCl 3 ) δ: 2.39 (3H, s), 7.00 (1H, d, J = 7.6 Hz), 7.29 (1H, d, J = 7.8 Hz), 7.46-7.51 (2H, m), 7.55 (1H, s), 8.00 (1H, br s), 8.13 (1H, dd, J = 8.8, 2.0 Hz), 8.20 (1H, d, J = 8.8 Hz), 8.26 (1H, dd, J = 8.3 , 1.3 Hz), 8.38 (1H, d, J = 2.0 Hz), 9.01 (1H, dd, J = 4.2, 1.6 Hz).
製造例７
　キノリン－６－カルボン酸３４６ｍｇ、４－ヘキシルアニリン３５５ｍｇ、ＷＳＣ５７５ｍｇ、１－ヒドロキシベンゾトリアゾール２７０ｍｇ及びトリエチルアミン０．２８ｍｌをＤＭＦ２．１ｍｌに加え、１００℃で４時間攪拌した。室温付近まで放冷した反応混合物に飽和食塩水を加え、酢酸エチルで抽出した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して４’－ヘキシル－キノリン－６－カルボン酸アニリド（以下、本発明化合物７と記す。）５２４ｍｇを得た。
　本発明化合物７
Figure JPOXMLDOC01-appb-C000017
 1H-NMR (CDCl3) δ: 0.86-0.92 (3H, m), 1.26-1.38 (6H, m), 1.57-1.66 (2H, m), 2.61 (2H, t, J = 7.7 Hz), 7.21 (2H, d, J = 8.2 Hz), 7.49 (1H, dd, J = 8.2, 4.2 Hz), 7.59 (2H, d, J = 8.2 Hz), 7.99 (1H, br s), 8.13 (1H, dd, J = 8.7, 1.9 Hz), 8.20 (1H, d, J = 8.7 Hz), 8.26 (1H, dd, J = 8.3, 1.0 Hz), 8.38 (1H, d, J = 1.6 Hz), 9.01 (1H, dd, J = 4.2, 1.6 Hz). Production Example 7
Quinoline-6-carboxylic acid (346 mg), 4-hexylaniline (355 mg), WSC (575 mg), 1-hydroxybenzotriazole (270 mg) and triethylamine (0.28 ml) were added to DMF (2.1 ml), and the mixture was stirred at 100 ° C. for 4 hours. Saturated brine was added to the reaction mixture which had been allowed to cool to near room temperature, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 524 mg of 4′-hexyl-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 7).
Compound 7 of the present invention
Figure JPOXMLDOC01-appb-C000017
 1 H-NMR (CDCl 3 ) δ: 0.86-0.92 (3H, m), 1.26-1.38 (6H, m), 1.57-1.66 (2H, m), 2.61 (2H, t, J = 7.7 Hz), 7.21 (2H, d, J = 8.2 Hz), 7.49 (1H, dd, J = 8.2, 4.2 Hz), 7.59 (2H, d, J = 8.2 Hz), 7.99 (1H, br s), 8.13 (1H, dd , J = 8.7, 1.9 Hz), 8.20 (1H, d, J = 8.7 Hz), 8.26 (1H, dd, J = 8.3, 1.0 Hz), 8.38 (1H, d, J = 1.6 Hz), 9.01 (1H , dd, J = 4.2, 1.6 Hz).
製造例８
　キノリン－６－カルボン酸３４６ｍｇ、４－フェノキシアニリン３７０ｍｇ、ＷＳＣ５７５ｍｇ、１－ヒドロキシベンゾトリアゾール１３５ｍｇ及びトリエチルアミン０．２８ｍｌをＤＭＦ２．１ｍｌに加え、１００℃で４時間攪拌した。室温付近まで放冷した反応混合物に飽和食塩水を加え、酢酸エチルで抽出した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して４’－フェノキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物８と記す。）４８７ｍｇを得た。
　本発明化合物８
Figure JPOXMLDOC01-appb-C000018
 1H-NMR (CDCl3) δ: 7.00-7.07 (4H, m), 7.08-7.13 (1H, m), 7.32-7.37 (2H, m), 7.48 (1H, dd, J = 8.3, 4.2 Hz), 7.65 (2H, d, J = 8.8 Hz), 8.11-8.15 (2H, m), 8.18 (1H, d, J = 8.8 Hz), 8.23 (1H, dd, J = 8.3, 1.6 Hz), 8.38 (1H, d, J = 1.8 Hz), 9.00 (1H, dd, J = 4.2, 1.6 Hz). Production Example 8
Quinoline-6-carboxylic acid (346 mg), 4-phenoxyaniline (370 mg), WSC (575 mg), 1-hydroxybenzotriazole (135 mg) and triethylamine (0.28 ml) were added to DMF (2.1 ml), followed by stirring at 100 ° C. for 4 hours. Saturated brine was added to the reaction mixture which had been allowed to cool to near room temperature, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 487 mg of 4′-phenoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 8).
Compound 8 of the present invention
Figure JPOXMLDOC01-appb-C000018
 1 H-NMR (CDCl 3 ) δ: 7.00-7.07 (4H, m), 7.08-7.13 (1H, m), 7.32-7.37 (2H, m), 7.48 (1H, dd, J = 8.3, 4.2 Hz) , 7.65 (2H, d, J = 8.8 Hz), 8.11-8.15 (2H, m), 8.18 (1H, d, J = 8.8 Hz), 8.23 (1H, dd, J = 8.3, 1.6 Hz), 8.38 ( 1H, d, J = 1.8 Hz), 9.00 (1H, dd, J = 4.2, 1.6 Hz).
製造例９
　キノリン－６－カルボン酸塩化物の塩酸塩０．２０ｇ、２－フルオロ－４－メチルアニリン０．１５ｇ及びトリエチルアミン０．２０ｇをクロロホルム３ｍｌに加え、室温で４時間攪拌した。反応混合物をシリカゲルカラムクロマトグラフィーに付して２’－フルオロ－４’－メチル－キノリン－６－カルボン酸アニリド（以下、本発明化合物９と記す。）０．１７ｇを得た。
　本発明化合物９
Figure JPOXMLDOC01-appb-C000019
 1H-NMR (CDCl3) δ: 2.36 (3H, s), 6.97-7.05 (2H, m), 7.52 (1H, dd, J = 8.3, 4.2 Hz), 8.13 (1H, br s), 8.17 (1H, dd, J = 8.7, 1.8 Hz), 8.23 (1H, d, J = 8.7 Hz), 8.29-8.37 (2H, m), 8.42 (1H, d, J = 1.8 Hz), 9.03 (1H, dd, J = 4.2, 1.8 Hz). Production Example 9
0.20 g of hydrochloride of quinoline-6-carboxylic acid chloride, 0.15 g of 2-fluoro-4-methylaniline and 0.20 g of triethylamine were added to 3 ml of chloroform, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was subjected to silica gel column chromatography to obtain 0.17 g of 2′-fluoro-4′-methyl-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 9).
Compound 9 of the present invention
Figure JPOXMLDOC01-appb-C000019
 1 H-NMR (CDCl 3 ) δ: 2.36 (3H, s), 6.97-7.05 (2H, m), 7.52 (1H, dd, J = 8.3, 4.2 Hz), 8.13 (1H, br s), 8.17 ( 1H, dd, J = 8.7, 1.8 Hz), 8.23 (1H, d, J = 8.7 Hz), 8.29-8.37 (2H, m), 8.42 (1H, d, J = 1.8 Hz), 9.03 (1H, dd , J = 4.2, 1.8 Hz).
製造例１０
キノリン－６－カルボン酸塩化物の塩酸塩０．２０ｇ、４－エチルアニリン０．１５ｇ及びトリエチルアミン０．２０ｇをクロロホルム３ｍｌに加え、室温で４時間攪拌した。反応混合物をシリカゲルカラムクロマトグラフィーに付して４’－エチル－キノリン－６－カルボン酸アニリド（以下、本発明化合物１０と記す。）０．１５ｇを得た。
　本発明化合物１０
Figure JPOXMLDOC01-appb-C000020
 1H-NMR (CDCl3) δ: 1.25 (3H, t, J = 7.6 Hz), 2.66 (2H, q, J = 7.6 Hz), 7.23 (2H, d, J = 8.4 Hz), 7.49 (1H, dd, J = 8.3, 4.2 Hz), 7.60 (2H, d, J = 8.4 Hz), 7.99 (1H, br s), 8.14 (1H, dd, J = 8.7, 2.1 Hz), 8.20 (1H, d, J = 8.7 Hz), 8.26 (1H, dd, J = 8.3, 1.4 Hz), 8.39 (1H, d, J = 1.8 Hz), 9.01 (1H, dd, J = 4.2, 1.8 Hz). Production Example 10
0.20 g of hydrochloride of quinoline-6-carboxylic acid chloride, 0.15 g of 4-ethylaniline and 0.20 g of triethylamine were added to 3 ml of chloroform, followed by stirring at room temperature for 4 hours. The reaction mixture was subjected to silica gel column chromatography to obtain 0.15 g of 4′-ethyl-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 10).
Compound 10 of the present invention
Figure JPOXMLDOC01-appb-C000020
 1 H-NMR (CDCl 3 ) δ: 1.25 (3H, t, J = 7.6 Hz), 2.66 (2H, q, J = 7.6 Hz), 7.23 (2H, d, J = 8.4 Hz), 7.49 (1H, dd, J = 8.3, 4.2 Hz), 7.60 (2H, d, J = 8.4 Hz), 7.99 (1H, br s), 8.14 (1H, dd, J = 8.7, 2.1 Hz), 8.20 (1H, d, J = 8.7 Hz), 8.26 (1H, dd, J = 8.3, 1.4 Hz), 8.39 (1H, d, J = 1.8 Hz), 9.01 (1H, dd, J = 4.2, 1.8 Hz).
製造例１１
　キノリン－６－カルボン酸塩化物の塩酸塩０．２０ｇ、４－プロピルアニリン０．１６ｇ及びトリエチルアミン０．２０ｇをクロロホルム３ｍｌに加え、室温で４時間攪拌した。反応混合物をシリカゲルカラムクロマトグラフィーに付して４’－プロピル－キノリン－６－カルボン酸アニリド（以下、本発明化合物１１と記す。）０．１９ｇを得た。
　本発明化合物１１
Figure JPOXMLDOC01-appb-C000021
 1H-NMR (CDCl3) δ: 0.95 (3H, t, J = 7.4 Hz), 1.60-1.70 (2H, m), 2.59 (2H, t, J = 7.5 Hz), 7.20 (2H, d, J = 8.5 Hz), 7.48 (1H, dd, J = 8.3, 4.3 Hz), 7.59 (2H, d, J = 8.5 Hz), 8.04 (1H, br s), 8.13 (1H, dd, J = 8.7, 1.9 Hz), 8.18 (1H, d, J = 8.7 Hz), 8.24 (1H, dd, J = 8.3, 1.1 Hz), 8.37 (1H, d, J = 1.7 Hz), 9.00 (1H, dd, J = 4.3, 1.7 Hz). Production Example 11
0.20 g of hydrochloride of quinoline-6-carboxylic acid chloride, 0.16 g of 4-propylaniline and 0.20 g of triethylamine were added to 3 ml of chloroform, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was subjected to silica gel column chromatography to obtain 0.19 g of 4′-propyl-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 11).
Compound 11 of the present invention
Figure JPOXMLDOC01-appb-C000021
 1 H-NMR (CDCl 3 ) δ: 0.95 (3H, t, J = 7.4 Hz), 1.60-1.70 (2H, m), 2.59 (2H, t, J = 7.5 Hz), 7.20 (2H, d, J = 8.5 Hz), 7.48 (1H, dd, J = 8.3, 4.3 Hz), 7.59 (2H, d, J = 8.5 Hz), 8.04 (1H, br s), 8.13 (1H, dd, J = 8.7, 1.9 Hz), 8.18 (1H, d, J = 8.7 Hz), 8.24 (1H, dd, J = 8.3, 1.1 Hz), 8.37 (1H, d, J = 1.7 Hz), 9.00 (1H, dd, J = 4.3 , 1.7 Hz).
製造例１２
　キノリン－６－カルボン酸塩化物の塩酸塩０．２０ｇ、４－ブチルアニリン０．１７ｇ及びトリエチルアミン０．２０ｇをクロロホルム３ｍｌに加え、室温で４時間攪拌した。反応混合物をシリカゲルカラムクロマトグラフィーに付して４’－ブチル－キノリン－６－カルボン酸アニリド（以下、本発明化合物１２と記す。）０．２２ｇを得た。
　本発明化合物１２
Figure JPOXMLDOC01-appb-C000022
 1H-NMR (CDCl3) δ: 0.94 (3H, t, J = 7.4 Hz), 1.32-1.41 (2H, m), 1.57-1.64 (2H, m), 2.62 (2H, t, J = 7.7 Hz), 7.21 (2H, d, J = 8.5 Hz), 7.49 (1H, dd, J = 8.4, 4.2 Hz), 7.59 (2H, d, J = 8.5 Hz), 7.98 (1H, br s), 8.13 (1H, dd, J = 8.8, 1.9 Hz), 8.20 (1H, d, J = 8.8 Hz), 8.26 (1H, dd, J = 8.3, 1.3 Hz), 8.38 (1H, d, J = 1.9 Hz), 9.01 (1H, dd, J = 4.2, 1.6 Hz). Production Example 12
0.20 g of hydrochloride of quinoline-6-carboxylic acid chloride, 0.17 g of 4-butylaniline and 0.20 g of triethylamine were added to 3 ml of chloroform, followed by stirring at room temperature for 4 hours. The reaction mixture was subjected to silica gel column chromatography to obtain 0.22 g of 4′-butyl-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 12).
Compound 12 of the present invention
Figure JPOXMLDOC01-appb-C000022
 1 H-NMR (CDCl 3 ) δ: 0.94 (3H, t, J = 7.4 Hz), 1.32-1.41 (2H, m), 1.57-1.64 (2H, m), 2.62 (2H, t, J = 7.7 Hz ), 7.21 (2H, d, J = 8.5 Hz), 7.49 (1H, dd, J = 8.4, 4.2 Hz), 7.59 (2H, d, J = 8.5 Hz), 7.98 (1H, br s), 8.13 ( 1H, dd, J = 8.8, 1.9 Hz), 8.20 (1H, d, J = 8.8 Hz), 8.26 (1H, dd, J = 8.3, 1.3 Hz), 8.38 (1H, d, J = 1.9 Hz), 9.01 (1H, dd, J = 4.2, 1.6 Hz).
製造例１３
　キノリン－６－カルボン酸塩化物の塩酸塩０．２０ｇ、４－ペンチルアニリン０．１８ｇ及びトリエチルアミン０．２０ｇをクロロホルム３ｍｌに加え、室温で４時間攪拌した。反応混合物をシリカゲルカラムクロマトグラフィーに付して４’－ペンチル－キノリン－６－カルボン酸アニリド（以下、本発明化合物１３と記す。）０．２１ｇを得た。
　本発明化合物１３
Figure JPOXMLDOC01-appb-C000023
 1H-NMR (CDCl3) δ: 0.90 (3H, t, J = 6.9 Hz), 1.29-1.38 (4H, m), 1.59-1.66 (2H, m), 2.61 (2H, t, J = 7.6 Hz), 7.21 (2H, d, J = 8.4 Hz), 7.49 (1H, dd, J = 8.3, 4.2 Hz), 7.59 (2H, d, J = 8.4 Hz), 7.99 (1H, br s), 8.13 (1H, dd, J = 8.7, 1.9 Hz), 8.20 (1H, d, J = 8.7 Hz), 8.26 (1H, dd, J = 8.3, 1.2 Hz), 8.38 (1H, d, J = 1.7 Hz), 9.01 (1H, dd, J = 4.2, 1.7 Hz). Production Example 13
0.20 g of hydrochloride of quinoline-6-carboxylic acid chloride, 0.18 g of 4-pentylaniline and 0.20 g of triethylamine were added to 3 ml of chloroform, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was subjected to silica gel column chromatography to obtain 0.21 g of 4′-pentyl-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 13).
Compound 13 of the present invention
Figure JPOXMLDOC01-appb-C000023
 1 H-NMR (CDCl 3 ) δ: 0.90 (3H, t, J = 6.9 Hz), 1.29-1.38 (4H, m), 1.59-1.66 (2H, m), 2.61 (2H, t, J = 7.6 Hz ), 7.21 (2H, d, J = 8.4 Hz), 7.49 (1H, dd, J = 8.3, 4.2 Hz), 7.59 (2H, d, J = 8.4 Hz), 7.99 (1H, br s), 8.13 ( 1H, dd, J = 8.7, 1.9 Hz), 8.20 (1H, d, J = 8.7 Hz), 8.26 (1H, dd, J = 8.3, 1.2 Hz), 8.38 (1H, d, J = 1.7 Hz), 9.01 (1H, dd, J = 4.2, 1.7 Hz).
製造例１４
　キノリン－６－カルボン酸塩化物の塩酸塩０．３０ｇ、３－メトキシ－４－メチルアニリン０．４０ｇ及びトリエチルアミン１．０ｇをクロロホルム５ｍｌに加え、室温で１時間攪拌した。反応混合物をシリカゲルカラムクロマトグラフィーに付して３’－メトキシ－４’－メチル－キノリン－６－カルボン酸アニリド（以下、本発明化合物１４と記す。）０．３６ｇを得た。
本発明化合物１４
Figure JPOXMLDOC01-appb-C000024
 1H-NMR (CDCl3) δ: 2.21 (3H, s), 3.87 (3H, s), 6.96 (1H, dd, J = 8.0, 2.2 Hz), 7.11 (1H, dd, J = 8.0, 0.5 Hz), 7.49 (1H, dd, J = 8.3, 4.2 Hz), 7.52 (1H, d, J = 1.4 Hz), 8.07 (1H, br s), 8.13 (1H, dd, J = 8.7, 1.9 Hz), 8.19 (1H, d, J = 8.7 Hz), 8.24 (1H, dd, J = 8.3, 1.8 Hz), 8.38 (1H, d, J = 1.9 Hz), 9.01 (1H, dd, J = 4.2, 1.8 Hz). Production Example 14
0.30 g of hydrochloride of quinoline-6-carboxylic acid chloride, 0.40 g of 3-methoxy-4-methylaniline and 1.0 g of triethylamine were added to 5 ml of chloroform and stirred at room temperature for 1 hour. The reaction mixture was subjected to silica gel column chromatography to obtain 0.36 g of 3′-methoxy-4′-methyl-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 14).
Compound 14 of the present invention
Figure JPOXMLDOC01-appb-C000024
 1 H-NMR (CDCl 3 ) δ: 2.21 (3H, s), 3.87 (3H, s), 6.96 (1H, dd, J = 8.0, 2.2 Hz), 7.11 (1H, dd, J = 8.0, 0.5 Hz ), 7.49 (1H, dd, J = 8.3, 4.2 Hz), 7.52 (1H, d, J = 1.4 Hz), 8.07 (1H, br s), 8.13 (1H, dd, J = 8.7, 1.9 Hz), 8.19 (1H, d, J = 8.7 Hz), 8.24 (1H, dd, J = 8.3, 1.8 Hz), 8.38 (1H, d, J = 1.9 Hz), 9.01 (1H, dd, J = 4.2, 1.8 Hz) ).
製造例１５
　キノリン－６－カルボン酸塩化物の塩酸塩０．３０ｇ、２－フルオロ－４－フェノキシアニリン０．５０ｇ及びトリエチルアミン０．５０ｇをクロロホルム２ｍｌに加え、室温で２時間攪拌した。反応液をシリカゲルカラムクロマトグラフィーに付して２’－フルオロ－４’－フェノキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物１５と記す。）０．５１ｇを得た。
　本発明化合物１５
Figure JPOXMLDOC01-appb-C000025
 1H-NMR (CDCl3) δ: 6.83-6.91 (2H, m), 7.04-7.08 (2H, m), 7.12-7.19 (1H, m), 7.35-7.41 (2H, m), 7.53 (1H, dd, J = 8.3, 4.2 Hz), 8.09-8.13 (1H, m), 8.17 (1H, dd, J = 8.8, 2.0 Hz), 8.24 (1H, d, J = 8.8 Hz), 8.29-8.33 (1H, m), 8.36-8.44 (2H, m), 9.04 (1H, dd, J = 4.2, 1.8 Hz). Production Example 15
0.30 g of hydrochloride of quinoline-6-carboxylic acid chloride, 0.50 g of 2-fluoro-4-phenoxyaniline and 0.50 g of triethylamine were added to 2 ml of chloroform, followed by stirring at room temperature for 2 hours. The reaction solution was subjected to silica gel column chromatography to obtain 0.51 g of 2′-fluoro-4′-phenoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 15).
Compound 15 of the present invention
Figure JPOXMLDOC01-appb-C000025
 1 H-NMR (CDCl 3 ) δ: 6.83-6.91 (2H, m), 7.04-7.08 (2H, m), 7.12-7.19 (1H, m), 7.35-7.41 (2H, m), 7.53 (1H, dd, J = 8.3, 4.2 Hz), 8.09-8.13 (1H, m), 8.17 (1H, dd, J = 8.8, 2.0 Hz), 8.24 (1H, d, J = 8.8 Hz), 8.29-8.33 (1H , m), 8.36-8.44 (2H, m), 9.04 (1H, dd, J = 4.2, 1.8 Hz).
製造例１６
　キノリン－６－カルボン酸塩化物の塩酸塩０．３０ｇ、４－（２－メチルエチル）アニリン０．２６ｇ及びトリエチルアミン０．４０ｇをクロロホルム３ｍｌに加え、室温で４時間攪拌した。反応混合物をシリカゲルカラムクロマトグラフィーに付して４’－（１－メチルエチル）－キノリン－６－カルボン酸アニリド（以下、本発明化合物１６と記す。）０．３６ｇを得た。
　本発明化合物１６
Figure JPOXMLDOC01-appb-C000026
 1H-NMR (CDCl3) δ: 1.26 (6H, d, J = 6.5 Hz), 2.87-2.97 (1H, m), 7.25 (2H, d, J = 8.2 Hz), 7.48 (1H, dd, J = 8.3, 4.2 Hz), 7.60 (2H, d, J = 8.2 Hz), 8.06 (1H, br s), 8.13 (1H, dd, J = 8.7, 1.8 Hz), 8.18 (1H, d, J = 8.7 Hz), 8.21-8.25 (1H, m), 8.37 (1H, d, J = 1.8 Hz), 9.00 (1H, dd, J = 4.2, 1.6 Hz). Production Example 16
0.30 g of hydrochloride of quinoline-6-carboxylic acid chloride, 0.26 g of 4- (2-methylethyl) aniline and 0.40 g of triethylamine were added to 3 ml of chloroform, followed by stirring at room temperature for 4 hours. The reaction mixture was subjected to silica gel column chromatography to obtain 0.36 g of 4 ′-(1-methylethyl) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 16).
Compound 16 of the present invention
Figure JPOXMLDOC01-appb-C000026
 1 H-NMR (CDCl 3 ) δ: 1.26 (6H, d, J = 6.5 Hz), 2.87-2.97 (1H, m), 7.25 (2H, d, J = 8.2 Hz), 7.48 (1H, dd, J = 8.3, 4.2 Hz), 7.60 (2H, d, J = 8.2 Hz), 8.06 (1H, br s), 8.13 (1H, dd, J = 8.7, 1.8 Hz), 8.18 (1H, d, J = 8.7 Hz), 8.21-8.25 (1H, m), 8.37 (1H, d, J = 1.8 Hz), 9.00 (1H, dd, J = 4.2, 1.6 Hz).
製造例１７
　キノリン－６－カルボン酸塩化物の塩酸塩０．３０ｇ、３，４－ジメチルアニリン０．２４ｇ及びトリエチルアミン０．４０ｇをクロロホルム３ｍｌに加え、室温で４時間攪拌した。反応混合物をシリカゲルカラムクロマトグラフィーに付して３’，４’－ジメチル－キノリン－６－カルボン酸アニリド（以下、本発明化合物１７と記す。）０．３２ｇを得た。
本発明化合物１７
Figure JPOXMLDOC01-appb-C000027
 1H-NMR (CDCl3) δ: 2.25 (3H, s), 2.27 (3H, s), 7.13 (1H, d, J = 8.0 Hz), 7.40 (1H, dd, J = 8.1, 1.8 Hz), 7.45-7.50 (2H, m), 8.03 (1H, br s), 8.12 (1H, dd, J = 8.8, 1.8 Hz), 8.17 (1H, d, J = 8.8 Hz), 8.22 (1H, dd, J = 8.5, 1.0 Hz), 8.36 (1H, d, J = 1.4 Hz), 9.00 (1H, dd, J = 4.3, 1.7 Hz). Production Example 17
0.30 g of hydrochloride of quinoline-6-carboxylic acid chloride, 0.24 g of 3,4-dimethylaniline and 0.40 g of triethylamine were added to 3 ml of chloroform, followed by stirring at room temperature for 4 hours. The reaction mixture was subjected to silica gel column chromatography to obtain 0.32 g of 3 ′, 4′-dimethyl-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 17).
Compound 17 of the present invention
Figure JPOXMLDOC01-appb-C000027
 1 H-NMR (CDCl 3 ) δ: 2.25 (3H, s), 2.27 (3H, s), 7.13 (1H, d, J = 8.0 Hz), 7.40 (1H, dd, J = 8.1, 1.8 Hz), 7.45-7.50 (2H, m), 8.03 (1H, br s), 8.12 (1H, dd, J = 8.8, 1.8 Hz), 8.17 (1H, d, J = 8.8 Hz), 8.22 (1H, dd, J = 8.5, 1.0 Hz), 8.36 (1H, d, J = 1.4 Hz), 9.00 (1H, dd, J = 4.3, 1.7 Hz).
製造例１８
　キノリン－６－カルボン酸塩化物の塩酸塩０．２５ｇ、４－（３－メトキシフェノキシ）アニリン０．２８ｇ及びトリエチルアミン０．４０ｇをクロロホルム３ｍｌに加え、室温で８時間攪拌した。反応混合物を減圧下濃縮し、得られた残渣を飽和炭酸水素ナトリウム水溶液、水、ＭＴＢＥ及びヘキサンで順次洗浄した後、乾燥して４’－（３－メトキシフェノキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物１８と記す。）０．４０ｇを得た。
　本発明化合物１８
Figure JPOXMLDOC01-appb-C000028
 1H-NMR (CDCl3) δ: 3.79 (3H, s), 6.56-6.61 (2H, m), 6.63-6.68 (1H, m), 7.03-7.09 (2H, m), 7.19-7.26 (1H, m), 7.49 (1H, dd, J = 8.3, 4.2 Hz), 7.66 (2H, d, J = 8.7 Hz), 8.04-8.27 (4H, m), 8.36-8.40 (1H, m), 9.01 (1H, dd, J = 4.2, 1.5 Hz). Production Example 18
0.25 g of hydrochloride of quinoline-6-carboxylic acid chloride, 0.28 g of 4- (3-methoxyphenoxy) aniline and 0.40 g of triethylamine were added to 3 ml of chloroform, and the mixture was stirred at room temperature for 8 hours. The reaction mixture was concentrated under reduced pressure, and the obtained residue was washed successively with saturated aqueous sodium hydrogen carbonate solution, water, MTBE and hexane and then dried to give 4 ′-(3-methoxyphenoxy) -quinoline-6-carboxylic acid anilide. (Hereinafter referred to as the present compound 18) 0.40 g was obtained.
Compound 18 of the present invention
Figure JPOXMLDOC01-appb-C000028
 1 H-NMR (CDCl 3 ) δ: 3.79 (3H, s), 6.56-6.61 (2H, m), 6.63-6.68 (1H, m), 7.03-7.09 (2H, m), 7.19-7.26 (1H, m), 7.49 (1H, dd, J = 8.3, 4.2 Hz), 7.66 (2H, d, J = 8.7 Hz), 8.04-8.27 (4H, m), 8.36-8.40 (1H, m), 9.01 (1H , dd, J = 4.2, 1.5 Hz).
製造例１９
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．４０ｇ、１－クロロ－４－ペンチン０．２０ｇ及び炭酸セシウム０．６４ｇをＤＭＦ２ｍｌに加え、８０℃で４時間攪拌した。室温付近まで放冷した反応混合物に水を加えて、クロロホルムで抽出した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して３’－（４－ペンチニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物１９と記す。）０．４５ｇを得た。
　本発明化合物１９
Figure JPOXMLDOC01-appb-C000029
 1H-NMR (CDCl3) δ: 1.98 (1H, t, J = 2.7 Hz), 1.99-2.06 (2H, m), 2.43 (2H, td, J = 7.0, 2.6 Hz), 4.12 (2H, t, J = 6.0 Hz), 6.75 (1H, dd, J = 8.2, 2.4 Hz), 7.14 (1H, t, J = 3.9 Hz), 7.26-7.31 (1H, m), 7.51 (2H, dd, J = 8.3, 4.1 Hz), 8.00 (1H, br s), 8.14 (1H, dd, J = 8.9, 2.1 Hz), 8.21 (1H, d, J = 8.9 Hz), 8.27 (1H, dd, J = 8.3, 1.3 Hz), 8.39 (1H, d, J = 1.9 Hz), 9.02 (1H, dd, J = 4.1, 1.8 Hz). Production Example 19
0.40 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.20 g of 1-chloro-4-pentyne and 0.64 g of cesium carbonate were added to 2 ml of DMF, and the mixture was stirred at 80 ° C. for 4 hours. Water was added to the reaction mixture allowed to cool to around room temperature, and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 0.45 g of 3 ′-(4-pentynyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 19).
Compound 19 of the present invention
Figure JPOXMLDOC01-appb-C000029
 1 H-NMR (CDCl 3 ) δ: 1.98 (1H, t, J = 2.7 Hz), 1.99-2.06 (2H, m), 2.43 (2H, td, J = 7.0, 2.6 Hz), 4.12 (2H, t , J = 6.0 Hz), 6.75 (1H, dd, J = 8.2, 2.4 Hz), 7.14 (1H, t, J = 3.9 Hz), 7.26-7.31 (1H, m), 7.51 (2H, dd, J = 8.3, 4.1 Hz), 8.00 (1H, br s), 8.14 (1H, dd, J = 8.9, 2.1 Hz), 8.21 (1H, d, J = 8.9 Hz), 8.27 (1H, dd, J = 8.3, 1.3 Hz), 8.39 (1H, d, J = 1.9 Hz), 9.02 (1H, dd, J = 4.1, 1.8 Hz).
製造例２０
　キノリン－６－カルボン酸塩化物の塩酸塩６８４ｍｇ、３－メチルチオアニリン４１８ｍｇ及びトリエチルアミン６６８ｍｇをＴＨＦ８ｍｌに加え、室温で８時間攪拌した。反応混合物に飽和炭酸水素ナトリウム水溶液を加えて、生成した固体を濾集した。得られた固体をシリカゲルカラムクロマトグラフィーに付して３’－メチルチオ－キノリン－６－カルボン酸アニリド（以下、本発明化合物２０と記す。）０．６１ｇを得た。
　本発明化合物２０
Figure JPOXMLDOC01-appb-C000030
 1H-NMR (CDCl3) δ: 2.50 (3H, s), 7.03-7.07 (1H, m), 7.29 (1H, d, J = 8.0 Hz), 7.39-7.43 (1H, m), 7.47 (1H, dd, J = 8.3, 4.2 Hz), 7.68-7.71 (1H, m), 8.09-8.23 (4H, m), 8.34-8.37 (1H, m), 8.99 (1H, dd, J = 4.2, 1.8 Hz). Production Example 20
684 mg of quinoline-6-carboxylic acid chloride hydrochloride, 418 mg of 3-methylthioaniline and 668 mg of triethylamine were added to 8 ml of THF, and the mixture was stirred at room temperature for 8 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the resulting solid was collected by filtration. The obtained solid was subjected to silica gel column chromatography to obtain 0.61 g of 3′-methylthio-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 20).
Compound 20 of the present invention
Figure JPOXMLDOC01-appb-C000030
 1 H-NMR (CDCl 3 ) δ: 2.50 (3H, s), 7.03-7.07 (1H, m), 7.29 (1H, d, J = 8.0 Hz), 7.39-7.43 (1H, m), 7.47 (1H , dd, J = 8.3, 4.2 Hz), 7.68-7.71 (1H, m), 8.09-8.23 (4H, m), 8.34-8.37 (1H, m), 8.99 (1H, dd, J = 4.2, 1.8 Hz ).
製造例２１
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド１．０ｇ、１－ブロモブタン１．３ｇ及び炭酸セシウム３．０ｇをＤＭＦ５ｍｌに加え、室温で４時間攪拌した。反応混合物に水を加えて、クロロホルムで抽出した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して３’－ブトキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物２１と記す。）０．２４ｇを得た。
　本発明化合物２１
Figure JPOXMLDOC01-appb-C000031
 1H-NMR (CDCl3) δ: 0.98 (3H, t, J = 7.4 Hz), 1.45-1.55 (2H, m), 1.74-1.82 (2H, m), 4.00 (2H, t, J = 6.5 Hz), 6.73 (1H, dd, J = 8.2, 2.4 Hz), 7.13 (1H, dd, J = 7.6, 1.6 Hz), 7.27 (1H, t, J = 8.2 Hz), 7.46-7.51 (2H, m), 8.05 (1H, br s), 8.13 (1H, dd, J = 8.8, 1.9 Hz), 8.19 (1H, d, J = 8.8 Hz), 8.25 (1H, dd, J = 8.3, 1.3 Hz), 8.38 (1H, d, J = 1.9 Hz), 9.01 (1H, dd, J = 4.3, 1.7 Hz). Production Example 21
1.0 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 1.3 g of 1-bromobutane and 3.0 g of cesium carbonate were added to 5 ml of DMF and stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 0.24 g of 3′-butoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 21).
Compound 21 of the present invention
Figure JPOXMLDOC01-appb-C000031
 1 H-NMR (CDCl 3 ) δ: 0.98 (3H, t, J = 7.4 Hz), 1.45-1.55 (2H, m), 1.74-1.82 (2H, m), 4.00 (2H, t, J = 6.5 Hz ), 6.73 (1H, dd, J = 8.2, 2.4 Hz), 7.13 (1H, dd, J = 7.6, 1.6 Hz), 7.27 (1H, t, J = 8.2 Hz), 7.46-7.51 (2H, m) , 8.05 (1H, br s), 8.13 (1H, dd, J = 8.8, 1.9 Hz), 8.19 (1H, d, J = 8.8 Hz), 8.25 (1H, dd, J = 8.3, 1.3 Hz), 8.38 (1H, d, J = 1.9 Hz), 9.01 (1H, dd, J = 4.3, 1.7 Hz).
製造例２２
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、１－ヨードプロパン０．２３ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－プロポキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物２２と記す。）０．２９ｇを得た。
　本発明化合物２２
Figure JPOXMLDOC01-appb-C000032
 1H-NMR (CDCl3) δ: 1.04 (3H, t, J = 7.4 Hz), 1.77-1.86 (2H, m), 3.95 (2H, t, J = 6.6 Hz), 6.73 (1H, dd, J = 8.1, 1.8 Hz), 7.14 (1H, d, J = 7.5 Hz), 7.24-7.29 (1H, m), 7.46-7.49 (2H, m), 8.11-8.19 (2H, m), 8.23 (2H, d, J = 8.2 Hz), 8.37 (1H, s), 8.99-9.01 (1H, m). Production Example 22
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.23 g of 1-iodopropane and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with a 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and dried with 3′-propoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as “anilide”). This is referred to as the present compound 22.) 0.29 g was obtained.
Compound 22 of the present invention
Figure JPOXMLDOC01-appb-C000032
 1 H-NMR (CDCl 3 ) δ: 1.04 (3H, t, J = 7.4 Hz), 1.77-1.86 (2H, m), 3.95 (2H, t, J = 6.6 Hz), 6.73 (1H, dd, J = 8.1, 1.8 Hz), 7.14 (1H, d, J = 7.5 Hz), 7.24-7.29 (1H, m), 7.46-7.49 (2H, m), 8.11-8.19 (2H, m), 8.23 (2H, d, J = 8.2 Hz), 8.37 (1H, s), 8.99-9.01 (1H, m).
製造例２３
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、１－ヨードペンタン０．２７及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－ペンチルオキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物２３と記す。）０．２７ｇを得た。
　本発明化合物２３
Figure JPOXMLDOC01-appb-C000033
 1H-NMR (CDCl3) δ: 0.93 (3H, t, J = 6.9 Hz), 1.36-1.48 (4H, m), 1.76-1.83 (2H, m), 3.98 (2H, t, J = 6.5 Hz), 6.72 (1H, d, J = 8.0 Hz), 7.14 (1H, d, J = 7.7 Hz), 7.24-7.28 (1H, m), 7.46-7.49 (2H, m), 8.11-8.18 (3H, m), 8.22 (1H, d, J = 8.2 Hz), 8.36 (1H, s), 8.99-9.00 (1H, m). Production Example 23
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.27 of 1-iodopentane and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3'-pentyloxy-quinoline-6-carboxylic acid anilide ( Hereinafter referred to as the present compound 23.) 0.27 g was obtained.
Compound 23 of the present invention
Figure JPOXMLDOC01-appb-C000033
 1 H-NMR (CDCl 3 ) δ: 0.93 (3H, t, J = 6.9 Hz), 1.36-1.48 (4H, m), 1.76-1.83 (2H, m), 3.98 (2H, t, J = 6.5 Hz ), 6.72 (1H, d, J = 8.0 Hz), 7.14 (1H, d, J = 7.7 Hz), 7.24-7.28 (1H, m), 7.46-7.49 (2H, m), 8.11-8.18 (3H, m), 8.22 (1H, d, J = 8.2 Hz), 8.36 (1H, s), 8.99-9.00 (1H, m).
製造例２４
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、シクロプロピルメチルブロマイド０．１８ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－シクロプロピルメトキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物２４と記す。）０．２８ｇを得た。
　本発明化合物２４
Figure JPOXMLDOC01-appb-C000034
 1H-NMR (CDCl3) δ: 0.35-0.39 (2H, m), 0.63-0.68 (2H, m), 1.25-1.34 (1H, m), 3.86 (2H, d, J = 6.8 Hz), 6.74-6.76 (1H, m), 7.12 (1H, d, J = 7.1 Hz), 7.26-7.30 (1H, m), 7.48-7.52 (2H, m), 7.96 (1H, s), 8.14 (1H, d, J = 8.5 Hz), 8.21 (1H, d, J = 9.0 Hz), 8.27 (1H, d, J = 8.0 Hz), 8.39 (1H, s), 9.02 (1H, d, J = 3.4 Hz). Production Example 24
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.18 g of cyclopropylmethyl bromide and 5 ml of DMF, 0.55 g of cesium carbonate was added and stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, and dried under reduced pressure to give 3'-cyclopropylmethoxy-quinoline-6-carboxylic acid anilide. (Hereinafter referred to as the present compound 24.) 0.28 g was obtained.
Compound 24 of the present invention
Figure JPOXMLDOC01-appb-C000034
 1 H-NMR (CDCl 3 ) δ: 0.35-0.39 (2H, m), 0.63-0.68 (2H, m), 1.25-1.34 (1H, m), 3.86 (2H, d, J = 6.8 Hz), 6.74 -6.76 (1H, m), 7.12 (1H, d, J = 7.1 Hz), 7.26-7.30 (1H, m), 7.48-7.52 (2H, m), 7.96 (1H, s), 8.14 (1H, d , J = 8.5 Hz), 8.21 (1H, d, J = 9.0 Hz), 8.27 (1H, d, J = 8.0 Hz), 8.39 (1H, s), 9.02 (1H, d, J = 3.4 Hz).
製造例２５
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、シクロブチルメチルブロマイド０．２０ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－シクロブチルメトキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物２５と記す。）０．１０ｇを得た。
　本発明化合物２５
Figure JPOXMLDOC01-appb-C000035
 1H-NMR (CDCl3) δ: 1.84-2.01 (4H, m), 2.11-2.18 (2H, m), 2.75-2.82 (1H, m), 3.98 (2H, d, J = 6.6 Hz), 6.74 (1H, d, J = 8.3 Hz), 7.12 (1H, d, J = 7.3 Hz), 7.25-7.29 (1H, m), 7.49-7.51 (2H, m), 8.00 (1H, s), 8.14 (1H, d, J = 8.8 Hz), 8.21 (1H, d, J = 9.0 Hz), 8.26 (1H, d, J = 8.5 Hz), 8.39 (1H, s), 9.02 (1H, d, J = 3.9 Hz). Production Example 25
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.20 g of cyclobutylmethyl bromide and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3'-cyclobutylmethoxy-quinoline-6-carboxylic acid anilide. (Hereinafter referred to as the present compound 25.) 0.10 g was obtained.
Compound 25 of the present invention
Figure JPOXMLDOC01-appb-C000035
 1 H-NMR (CDCl 3 ) δ: 1.84-2.01 (4H, m), 2.11-2.18 (2H, m), 2.75-2.82 (1H, m), 3.98 (2H, d, J = 6.6 Hz), 6.74 (1H, d, J = 8.3 Hz), 7.12 (1H, d, J = 7.3 Hz), 7.25-7.29 (1H, m), 7.49-7.51 (2H, m), 8.00 (1H, s), 8.14 ( 1H, d, J = 8.8 Hz), 8.21 (1H, d, J = 9.0 Hz), 8.26 (1H, d, J = 8.5 Hz), 8.39 (1H, s), 9.02 (1H, d, J = 3.9 Hz).
製造例２６
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、１－ブロモ－３－メトキシプロパン０．２１ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（３－メトキシ）プロポキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物２６と記す。）０．１３ｇを得た。
　本発明化合物２６
Figure JPOXMLDOC01-appb-C000036
 1H-NMR (CDCl3) δ: 2.04-2.10 (2H, m), 3.37 (3H, s), 3.57 (2H, t, J = 6.2 Hz), 4.11 (2H, t, J = 6.3 Hz), 6.74 (1H, dd, J = 8.2, 2.3 Hz), 7.13-7.15 (1H, m), 7.25-7.30 (1H, m), 7.47 (1H, t, J = 2.1 Hz), 7.51 (1H, dd, J = 8.3, 4.1 Hz), 7.94 (1H, s), 8.14 (1H, dd, J = 8.8, 2.0 Hz), 8.22 (1H, d, J = 8.8 Hz), 8.29 (1H, d, J = 8.3 Hz), 8.39 (1H, d, J = 1.7 Hz), 9.02 (1H, dd, J = 4.1, 1.7 Hz). Production Example 26
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.21 g of 1-bromo-3-methoxypropane and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, and dried under reduced pressure to give 3 '-(3-methoxy) propoxy-quinoline-6- 0.13 g of carboxylic acid anilide (hereinafter referred to as the present compound 26) was obtained.
Compound 26 of the present invention
Figure JPOXMLDOC01-appb-C000036
 1 H-NMR (CDCl 3 ) δ: 2.04-2.10 (2H, m), 3.37 (3H, s), 3.57 (2H, t, J = 6.2 Hz), 4.11 (2H, t, J = 6.3 Hz), 6.74 (1H, dd, J = 8.2, 2.3 Hz), 7.13-7.15 (1H, m), 7.25-7.30 (1H, m), 7.47 (1H, t, J = 2.1 Hz), 7.51 (1H, dd, J = 8.3, 4.1 Hz), 7.94 (1H, s), 8.14 (1H, dd, J = 8.8, 2.0 Hz), 8.22 (1H, d, J = 8.8 Hz), 8.29 (1H, d, J = 8.3 Hz), 8.39 (1H, d, J = 1.7 Hz), 9.02 (1H, dd, J = 4.1, 1.7 Hz).
製造例２７
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、４－メトキシブチルメタンスルホネート０．２５ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（４－メトキシ）ブトキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物２７と記す。）０．１７ｇを得た。
　本発明化合物２７
Figure JPOXMLDOC01-appb-C000037
 1H-NMR (CDCl3) δ: 1.74-1.80 (2H, m), 1.85-1.91 (2H, m), 3.36 (3H, s), 3.46 (2H, t, J = 6.1 Hz), 4.03 (2H, t, J = 6.2 Hz), 6.73 (1H, d, J = 8.3 Hz), 7.14 (1H, d, J = 8.0 Hz), 7.26-7.30 (1H, m), 7.46 (1H, s), 7.51 (1H, dd, J = 7.9, 4.0 Hz), 7.98 (1H, s), 8.14 (1H, d, J = 8.5 Hz), 8.21 (1H, d, J = 8.8 Hz), 8.28 (1H, d, J = 8.0 Hz), 8.39 (1H, s), 9.02 (1H, d, J = 3.2 Hz). Production Example 27
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.25 g of 4-methoxybutylmethanesulfonate and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 '-(4-methoxy) butoxy-quinoline-6- 0.17 g of carboxylic acid anilide (hereinafter referred to as the present compound 27) was obtained.
Compound 27 of the present invention
Figure JPOXMLDOC01-appb-C000037
 1 H-NMR (CDCl 3) δ: 1.74-1.80 (2H, m), 1.85-1.91 (2H, m), 3.36 (3H, s), 3.46 (2H, t, J = 6.1 Hz), 4.03 (2H , t, J = 6.2 Hz), 6.73 (1H, d, J = 8.3 Hz), 7.14 (1H, d, J = 8.0 Hz), 7.26-7.30 (1H, m), 7.46 (1H, s), 7.51 (1H, dd, J = 7.9, 4.0 Hz), 7.98 (1H, s), 8.14 (1H, d, J = 8.5 Hz), 8.21 (1H, d, J = 8.8 Hz), 8.28 (1H, d, J = 8.0 Hz), 8.39 (1H, s), 9.02 (1H, d, J = 3.2 Hz).
製造例２８
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、３－エトキシプロピルメタンスルホネート０．２５ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（３－エトキシ）プロポキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物２８と記す。）０．１５ｇを得た。
　本発明化合物２８
Figure JPOXMLDOC01-appb-C000038
 1H-NMR (CDCl3) δ: 1.21 (3H, t, J = 7.1 Hz), 2.04-2.10 (2H, m), 3.50 (2H, q, J = 7.0 Hz), 3.61 (2H, t, J = 6.2 Hz), 4.10 (2H, t, J = 6.2 Hz), 6.74 (1H, dd, J = 8.3, 2.4 Hz), 7.14-7.16 (1H, m), 7.28 (1H, t, J = 8.0 Hz), 7.46 (1H, t, J = 2.0 Hz), 7.50 (1H, dd, J = 8.3, 4.1 Hz), 8.03 (1H, s), 8.13 (1H, dd, J = 8.8, 2.2 Hz), 8.20 (1H, d, J = 8.8 Hz), 8.25-8.27 (1H, m), 8.38 (1H, d, J = 2.0 Hz), 9.01 (1H, dd, J = 4.1, 1.7 Hz). Production Example 28
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.25 g of 3-ethoxypropyl methanesulfonate and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 '-(3-ethoxy) propoxy-quinoline-6- 0.15 g of carboxylic acid anilide (hereinafter referred to as the present compound 28) was obtained.
Compound 28 of the present invention
Figure JPOXMLDOC01-appb-C000038
 1 H-NMR (CDCl 3 ) δ: 1.21 (3H, t, J = 7.1 Hz), 2.04-2.10 (2H, m), 3.50 (2H, q, J = 7.0 Hz), 3.61 (2H, t, J = 6.2 Hz), 4.10 (2H, t, J = 6.2 Hz), 6.74 (1H, dd, J = 8.3, 2.4 Hz), 7.14-7.16 (1H, m), 7.28 (1H, t, J = 8.0 Hz ), 7.46 (1H, t, J = 2.0 Hz), 7.50 (1H, dd, J = 8.3, 4.1 Hz), 8.03 (1H, s), 8.13 (1H, dd, J = 8.8, 2.2 Hz), 8.20 (1H, d, J = 8.8 Hz), 8.25-8.27 (1H, m), 8.38 (1H, d, J = 2.0 Hz), 9.01 (1H, dd, J = 4.1, 1.7 Hz).
製造例２９
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、２－ヨードプロパン０．２３ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（１－メチル）エトキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物２９と記す。）０．１８ｇを得た。
　本発明化合物２９
Figure JPOXMLDOC01-appb-C000039
 1H-NMR (CDCl3) δ: 1.37 (6H, d, J = 6.1 Hz), 4.58-4.64 (1H, m), 6.73 (1H, dd, J = 7.9, 2.1 Hz), 7.11-7.13 (1H, m), 7.25-7.30 (1H, m), 7.46 (1H, s), 7.51 (1H, dd, J = 8.3, 4.1 Hz), 7.95 (1H, s), 8.14 (1H, dd, J = 8.8, 2.0 Hz), 8.21 (1H, d, J = 8.8 Hz), 8.28 (1H, d, J = 7.6 Hz), 8.39 (1H, d, J = 2.0 Hz), 9.02 (1H, dd, J = 4.1, 1.7 Hz). Production Example 29
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.23 g of 2-iodopropane and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 '-(1-methyl) ethoxy-quinoline-6- 0.18 g of carboxylic acid anilide (hereinafter referred to as the present compound 29) was obtained.
Compound 29 of the present invention
Figure JPOXMLDOC01-appb-C000039
 1 H-NMR (CDCl 3 ) δ: 1.37 (6H, d, J = 6.1 Hz), 4.58-4.64 (1H, m), 6.73 (1H, dd, J = 7.9, 2.1 Hz), 7.11-7.13 (1H , m), 7.25-7.30 (1H, m), 7.46 (1H, s), 7.51 (1H, dd, J = 8.3, 4.1 Hz), 7.95 (1H, s), 8.14 (1H, dd, J = 8.8 , 2.0 Hz), 8.21 (1H, d, J = 8.8 Hz), 8.28 (1H, d, J = 7.6 Hz), 8.39 (1H, d, J = 2.0 Hz), 9.02 (1H, dd, J = 4.1 , 1.7 Hz).
製造例３０
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、１－ブロモ－２－メチルプロパン０．１９ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（２－メチル）プロポキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物３０と記す。）０．２１ｇを得た。
　本発明化合物３０
Figure JPOXMLDOC01-appb-C000040
 1H-NMR (CDCl3) δ: 1.03 (6H, d, J = 6.6 Hz), 2.07-2.14 (1H, m), 3.77 (2H, d, J = 6.6 Hz), 6.74 (1H, d, J = 8.3 Hz), 7.12 (1H, d, J = 7.1 Hz), 7.26-7.29 (1H, m), 7.49-7.51 (2H, m), 8.02 (1H, s), 8.13 (1H, d, J = 9.3 Hz), 8.20 (1H, d, J = 8.8 Hz), 8.26 (1H, d, J = 8.3 Hz), 8.38 (1H, s), 9.02 (1H, d, J = 2.9 Hz). Production Example 30
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.19 g of 1-bromo-2-methylpropane and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 '-(2-methyl) propoxy-quinoline-6- 0.21 g of carboxylic acid anilide (hereinafter referred to as the present compound 30) was obtained.
Compound 30 of the present invention
Figure JPOXMLDOC01-appb-C000040
 1 H-NMR (CDCl 3 ) δ: 1.03 (6H, d, J = 6.6 Hz), 2.07-2.14 (1H, m), 3.77 (2H, d, J = 6.6 Hz), 6.74 (1H, d, J = 8.3 Hz), 7.12 (1H, d, J = 7.1 Hz), 7.26-7.29 (1H, m), 7.49-7.51 (2H, m), 8.02 (1H, s), 8.13 (1H, d, J = 9.3 Hz), 8.20 (1H, d, J = 8.8 Hz), 8.26 (1H, d, J = 8.3 Hz), 8.38 (1H, s), 9.02 (1H, d, J = 2.9 Hz).
製造例３１
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、２－ブロモブタン０．１９ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（１－メチル）プロポキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物３１と記す。）０．１９ｇを得た。
　本発明化合物３１
Figure JPOXMLDOC01-appb-C000041
 1H-NMR (CDCl3) δ: 0.99 (3H, t, J = 6.8 Hz), 1.32 (3H, d, J = 5.1 Hz), 1.62-1.80 (2H, m), 4.33-4.38 (1H, m), 6.72 (1H, d, J = 7.1 Hz), 7.13 (1H, d, J = 7.1 Hz), 7.25-7.28 (1H, m), 7.47-7.50 (2H, m), 8.05 (1H, s), 8.13 (1H, d, J = 7.8 Hz), 8.19 (1H, d, J = 8.5 Hz), 8.25 (1H, d, J = 7.6 Hz), 8.38 (1H, s), 9.01 (1H, s). Production Example 31
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.19 g of 2-bromobutane and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 '-(1-methyl) propoxy-quinoline-6- 0.19 g of carboxylic acid anilide (hereinafter referred to as the present compound 31) was obtained.
Compound 31 of the present invention
Figure JPOXMLDOC01-appb-C000041
 1 H-NMR (CDCl 3 ) δ: 0.99 (3H, t, J = 6.8 Hz), 1.32 (3H, d, J = 5.1 Hz), 1.62-1.80 (2H, m), 4.33-4.38 (1H, m ), 6.72 (1H, d, J = 7.1 Hz), 7.13 (1H, d, J = 7.1 Hz), 7.25-7.28 (1H, m), 7.47-7.50 (2H, m), 8.05 (1H, s) , 8.13 (1H, d, J = 7.8 Hz), 8.19 (1H, d, J = 8.5 Hz), 8.25 (1H, d, J = 7.6 Hz), 8.38 (1H, s), 9.01 (1H, s) .
製造例３２
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、１－ブロモ－２－エトキシエタン０．２３ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（３－エトキシ）エトキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物３２と記す。）０．３４ｇを得た。
　本発明化合物３２
Figure JPOXMLDOC01-appb-C000042
 1H-NMR (CDCl3) δ: 1.25 (3H, t, J = 6.8 Hz), 3.61 (2H, q, J = 6.8 Hz), 3.80-3.82 (2H, m), 4.15-4.17 (2H, m), 6.76 (1H, d, J = 7.8 Hz), 7.16 (1H, d, J = 7.3 Hz), 7.25-7.29 (1H, m), 7.47-7.50 (2H, m), 8.11-8.19 (3H, m), 8.24 (1H, d, J = 8.0 Hz), 8.37 (1H, s), 9.00 (1H, d, J = 2.7 Hz). Production Example 32
To a mixture of 0.3 'g of 3'-hydroxy-quinoline-6-carboxylic acid anilide, 0.23 g of 1-bromo-2-ethoxyethane and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 '-(3-ethoxy) ethoxy-quinoline-6- 0.34 g of carboxylic acid anilide (hereinafter referred to as the present compound 32) was obtained.
Compound 32 of the present invention
Figure JPOXMLDOC01-appb-C000042
 1 H-NMR (CDCl 3 ) δ: 1.25 (3H, t, J = 6.8 Hz), 3.61 (2H, q, J = 6.8 Hz), 3.80-3.82 (2H, m), 4.15-4.17 (2H, m ), 6.76 (1H, d, J = 7.8 Hz), 7.16 (1H, d, J = 7.3 Hz), 7.25-7.29 (1H, m), 7.47-7.50 (2H, m), 8.11-8.19 (3H, m), 8.24 (1H, d, J = 8.0 Hz), 8.37 (1H, s), 9.00 (1H, d, J = 2.7 Hz).
製造例３３
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、３－クロロ－１－プロペン０．１１ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（２－プロペニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物３３と記す。）０．２５ｇを得た。
　本発明化合物３３
Figure JPOXMLDOC01-appb-C000043
 1H-NMR (CDCl3) δ: 4.59 (2H, d, J = 4.1 Hz), 5.31 (1H, d, J = 10.5 Hz), 5.45 (1H, d, J = 17.3 Hz), 6.03-6.13 (1H, m), 6.76 (1H, d, J = 8.3 Hz), 7.14 (1H, d, J = 7.8 Hz), 7.26-7.31 (1H, m), 7.49-7.52 (2H, m), 7.98 (1H, s), 8.14 (1H, d, J = 9.0 Hz), 8.21 (1H, d, J = 8.5 Hz), 8.27 (1H, d, J = 8.0 Hz), 8.39 (1H, s), 9.02 (1H, d, J = 3.9 Hz). Production Example 33
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.11 g of 3-chloro-1-propene and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 ′-(2-propenyloxy) -quinoline-6-. 0.25 g of carboxylic acid anilide (hereinafter referred to as the present compound 33) was obtained.
Compound 33 of the present invention
Figure JPOXMLDOC01-appb-C000043
 1 H-NMR (CDCl 3 ) δ: 4.59 (2H, d, J = 4.1 Hz), 5.31 (1H, d, J = 10.5 Hz), 5.45 (1H, d, J = 17.3 Hz), 6.03-6.13 ( 1H, m), 6.76 (1H, d, J = 8.3 Hz), 7.14 (1H, d, J = 7.8 Hz), 7.26-7.31 (1H, m), 7.49-7.52 (2H, m), 7.98 (1H , s), 8.14 (1H, d, J = 9.0 Hz), 8.21 (1H, d, J = 8.5 Hz), 8.27 (1H, d, J = 8.0 Hz), 8.39 (1H, s), 9.02 (1H , d, J = 3.9 Hz).
製造例３４
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、１－ブロモ－２－ブテン０．２０ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（２－ブテニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物３４と記す。）０．１６ｇを得た。
　本発明化合物３４
Figure JPOXMLDOC01-appb-C000044
 1H-NMR (CDCl3) δ: 1.76-1.78 (3.0H, m), 4.50 (1.6H, d, J = 5.9 Hz), 4.64 (0.4H, d, J = 5.4 Hz), 5.71-5.80 (1.2H, m), 5.84-5.93 (0.8H, m), 6.73-6.77 (1.0H, m), 7.14-7.16 (1.0H, m), 7.25-7.30 (1.0H, m), 7.47-7.50 (2.0H, m), 8.05 (1.0H, s), 8.12 (1.0H, dd, J = 8.8, 2.0 Hz), 8.19 (1.0H, d, J = 8.8 Hz), 8.25 (1.0H, d, J = 8.3 Hz), 8.37 (1.0H, d, J = 2.0 Hz), 9.01 (1.0H, dd, J = 4.1, 1.7 Hz). Production Example 34
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.20 g of 1-bromo-2-butene and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, and dried under reduced pressure to give 3 '-(2-butenyloxy) -quinoline-6-carvone. 0.16 g of acid anilide (hereinafter referred to as the present compound 34) was obtained.
Compound 34 of the present invention
Figure JPOXMLDOC01-appb-C000044
 1 H-NMR (CDCl 3 ) δ: 1.76-1.78 (3.0H, m), 4.50 (1.6H, d, J = 5.9 Hz), 4.64 (0.4H, d, J = 5.4 Hz), 5.71-5.80 ( 1.2H, m), 5.84-5.93 (0.8H, m), 6.73-6.77 (1.0H, m), 7.14-7.16 (1.0H, m), 7.25-7.30 (1.0H, m), 7.47-7.50 ( 2.0H, m), 8.05 (1.0H, s), 8.12 (1.0H, dd, J = 8.8, 2.0 Hz), 8.19 (1.0H, d, J = 8.8 Hz), 8.25 (1.0H, d, J = 8.3 Hz), 8.37 (1.0H, d, J = 2.0 Hz), 9.01 (1.0H, dd, J = 4.1, 1.7 Hz).
製造例３５
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、１－ブロモ－２－ペンテン０．２２ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（２－ペンテニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物３５と記す。）０．３２ｇを得た。
　本発明化合物３５
Figure JPOXMLDOC01-appb-C000045
 1H-NMR (CDCl3) δ: 1.02-1.06 (3.0H, m), 2.09-2.21 (2.0H, m), 4.53 (1.2H, d, J = 5.6 Hz), 4.63 (0.8H, d, J = 4.1 Hz), 5.69-5.96 (2.0H, m), 6.74-6.77 (1.0H, m), 7.15 (1.0H, d, J = 7.8 Hz), 7.26-7.30 (1.0H, m), 7.48-7.52 (2.0H, m), 7.95 (1.0H, s), 8.14 (1.0H, d, J = 8.8 Hz), 8.22 (1.0H, d, J = 8.8 Hz), 8.28 (1.0H, d, J = 7.8 Hz), 8.39 (1.0H, s), 9.02 (1.0H, d, J = 3.4 Hz). Production Example 35
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.22 g of 1-bromo-2-pentene and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 '-(2-pentenyloxy) -quinoline-6- 0.32 g of carboxylic acid anilide (hereinafter referred to as the present compound 35) was obtained.
Compound 35 of the present invention
Figure JPOXMLDOC01-appb-C000045
 1 H-NMR (CDCl 3 ) δ: 1.02-1.06 (3.0H, m), 2.09-2.21 (2.0H, m), 4.53 (1.2H, d, J = 5.6 Hz), 4.63 (0.8H, d, J = 4.1 Hz), 5.69-5.96 (2.0H, m), 6.74-6.77 (1.0H, m), 7.15 (1.0H, d, J = 7.8 Hz), 7.26-7.30 (1.0H, m), 7.48 -7.52 (2.0H, m), 7.95 (1.0H, s), 8.14 (1.0H, d, J = 8.8 Hz), 8.22 (1.0H, d, J = 8.8 Hz), 8.28 (1.0H, d, J = 7.8 Hz), 8.39 (1.0H, s), 9.02 (1.0H, d, J = 3.4 Hz).
製造例３６
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、５－ブロモ－１－ペンテン０．２２ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（４－ペンテニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物３６と記す。）０．３３ｇを得た。
　本発明化合物３６
Figure JPOXMLDOC01-appb-C000046
 1H-NMR (CDCl3) δ: 1.87-1.94 (2H, m), 2.23-2.28 (2H, m), 4.02 (2H, t, J = 6.3 Hz), 5.01 (1H, d, J = 10.2 Hz), 5.08 (1H, dd, J = 17.1, 1.5 Hz), 5.82-5.92 (1H, m), 6.74 (1H, dd, J = 8.2, 2.3 Hz), 7.13 (1H, d, J = 7.8 Hz), 7.28 (1H, t, J = 10.0 Hz), 7.47-7.52 (2H, m), 7.97 (1H, s), 8.14 (1H, dd, J = 8.8, 2.0 Hz), 8.21 (1H, d, J = 8.8 Hz), 8.27 (1H, d, J = 8.0 Hz), 8.39 (1H, d, J = 2.0 Hz), 9.02 (1H, dd, J = 4.3, 1.6 Hz). Production Example 36
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.22 g of 5-bromo-1-pentene and 5 ml of DMF, 0.55 g of cesium carbonate was added and stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with a 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 '-(4-pentenyloxy) -quinoline-6-. 0.33 g of carboxylic acid anilide (hereinafter referred to as the present compound 36) was obtained.
Compound 36 of the present invention
Figure JPOXMLDOC01-appb-C000046
 1 H-NMR (CDCl 3 ) δ: 1.87-1.94 (2H, m), 2.23-2.28 (2H, m), 4.02 (2H, t, J = 6.3 Hz), 5.01 (1H, d, J = 10.2 Hz ), 5.08 (1H, dd, J = 17.1, 1.5 Hz), 5.82-5.92 (1H, m), 6.74 (1H, dd, J = 8.2, 2.3 Hz), 7.13 (1H, d, J = 7.8 Hz) , 7.28 (1H, t, J = 10.0 Hz), 7.47-7.52 (2H, m), 7.97 (1H, s), 8.14 (1H, dd, J = 8.8, 2.0 Hz), 8.21 (1H, d, J = 8.8 Hz), 8.27 (1H, d, J = 8.0 Hz), 8.39 (1H, d, J = 2.0 Hz), 9.02 (1H, dd, J = 4.3, 1.6 Hz).
製造例３７
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、６－ブロモ－１－ヘキセン０．２４ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（５－ヘキセニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物３７と記す。）０．３４ｇを得た。
　本発明化合物３７
Figure JPOXMLDOC01-appb-C000047
 1H-NMR (CDCl3) δ: 1.54-1.62 (2H, m), 1.78-1.85 (2H, m), 2.11-2.17 (2H, m), 4.01 (2H, t, J = 6.5 Hz), 4.96-4.99 (1H, m), 5.04 (1H, d, J = 17.1 Hz), 5.79-5.89 (1H, m), 6.73 (1H, dd, J = 8.3, 2.4 Hz), 7.13 (1H, d, J = 7.1 Hz), 7.27 (1H, t, J = 8.2 Hz), 7.48-7.51 (2H, m), 8.03 (1H, s), 8.13 (1H, dd, J = 8.8, 1.7 Hz), 8.19 (1H, d, J = 8.8 Hz), 8.25 (1H, d, J = 7.8 Hz), 8.38 (1H, d, J = 1.7 Hz), 9.00-9.02 (1H, m). Production Example 37
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.24 g of 6-bromo-1-hexene and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 '-(5-hexenyloxy) -quinoline-6-. 0.34 g of carboxylic acid anilide (hereinafter referred to as the present compound 37) was obtained.
Compound 37 of the present invention
Figure JPOXMLDOC01-appb-C000047
 1 H-NMR (CDCl 3 ) δ: 1.54-1.62 (2H, m), 1.78-1.85 (2H, m), 2.11-2.17 (2H, m), 4.01 (2H, t, J = 6.5 Hz), 4.96 -4.99 (1H, m), 5.04 (1H, d, J = 17.1 Hz), 5.79-5.89 (1H, m), 6.73 (1H, dd, J = 8.3, 2.4 Hz), 7.13 (1H, d, J = 7.1 Hz), 7.27 (1H, t, J = 8.2 Hz), 7.48-7.51 (2H, m), 8.03 (1H, s), 8.13 (1H, dd, J = 8.8, 1.7 Hz), 8.19 (1H , d, J = 8.8 Hz), 8.25 (1H, d, J = 7.8 Hz), 8.38 (1H, d, J = 1.7 Hz), 9.00-9.02 (1H, m).
製造例３８
　[１，５]－ナフチリジン－２－カルボン酸３４８ｍｇ、４－メチルアニリン２１４ｍｇ、ＢＯＰ試薬８８４ｍｇ及びトリエチルアミン１．０ｇをＤＭＦ１ｍｌに加え、室温で３時間攪拌した後、一晩放置した。反応混合物に酢酸エチルを加え、水及び飽和炭酸水素ナトリウム水溶液で順次洗浄した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して４’－メチル－[１，５]－ナフチリジン－２－カルボン酸アニリド（以下、本発明化合物３８と記す。）１９３ｍｇを得た。
　本発明化合物３８
Figure JPOXMLDOC01-appb-C000048
 1H-NMR (CDCl3) δ: 2.37 (3H, s), 7.23 (2H, d, J = 8.1 Hz), 7.71-7.76 (3H, m), 8.48-8.51 (1H, m), 8.60 (1H, d, J = 9.1 Hz), 8.65 (1H, d, J = 8.6 Hz), 9.09 (1H, dd, J = 4.2, 1.6 Hz), 10.05 (1H, br s). Production Example 38
348 mg of [1,5] -naphthyridine-2-carboxylic acid, 214 mg of 4-methylaniline, 884 mg of BOP reagent and 1.0 g of triethylamine were added to 1 ml of DMF, stirred at room temperature for 3 hours, and then left overnight. Ethyl acetate was added to the reaction mixture, and the mixture was washed successively with water and saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 193 mg of 4′-methyl- [1,5] -naphthyridine-2-carboxylic acid anilide (hereinafter referred to as the present compound 38).
Compound 38 of the present invention
Figure JPOXMLDOC01-appb-C000048
 1 H-NMR (CDCl 3 ) δ: 2.37 (3H, s), 7.23 (2H, d, J = 8.1 Hz), 7.71-7.76 (3H, m), 8.48-8.51 (1H, m), 8.60 (1H , d, J = 9.1 Hz), 8.65 (1H, d, J = 8.6 Hz), 9.09 (1H, dd, J = 4.2, 1.6 Hz), 10.05 (1H, br s).
製造例３９
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド０．２０ｇ、１－クロロ－４－ペンチン８０ｍｇ及び炭酸セシウム０．３０ｇをＤＭＦ２ｍｌに加え、室温で２０時間攪拌した。反応混合物に水を加えて、酢酸エチルで抽出した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２’－フルオロ－３’－（４－ペンチニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物３９と記す。）５４ｍｇを得た。
本発明化合物３９
Figure JPOXMLDOC01-appb-C000049
 1H-NMR (CDCl3) δ: 1.99 (1H, t, J = 2.6 Hz), 2.03-2.09 (2H, m), 2.46 (2H, td, J = 6.9, 2.6 Hz), 4.19 (2H, t, J = 6.1 Hz), 6.82 (1H, td, J = 8.2, 1.4 Hz), 7.12 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.1 Hz), 8.07-8.11 (1H, m), 8.16-8.25 (3H, m), 8.31 (1H, dd, J = 8.2, 1.3 Hz), 8.42 (1H, d, J = 1.7 Hz), 9.03 (1H, dd, J = 4.4, 1.7 Hz). Production Example 39
2'-Fluoro-3'-hydroxy-quinoline-6-carboxylic acid anilide (0.20 g), 1-chloro-4-pentine (80 mg) and cesium carbonate (0.30 g) were added to DMF (2 ml), and the mixture was stirred at room temperature for 20 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 54 mg of 2′-fluoro-3 ′-(4-pentynyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 39). It was.
Compound 39 of the present invention
Figure JPOXMLDOC01-appb-C000049
 1 H-NMR (CDCl 3 ) δ: 1.99 (1H, t, J = 2.6 Hz), 2.03-2.09 (2H, m), 2.46 (2H, td, J = 6.9, 2.6 Hz), 4.19 (2H, t , J = 6.1 Hz), 6.82 (1H, td, J = 8.2, 1.4 Hz), 7.12 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.1 Hz), 8.07 -8.11 (1H, m), 8.16-8.25 (3H, m), 8.31 (1H, dd, J = 8.2, 1.3 Hz), 8.42 (1H, d, J = 1.7 Hz), 9.03 (1H, dd, J = 4.4, 1.7 Hz).
製造例４０
　３'－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、３－ブロモ－１－プロピン０．２０ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（２－プロピニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物４０と記す。）０．２８ｇを得た。
　本発明化合物４０
Figure JPOXMLDOC01-appb-C000050
 1H-NMR (CDCl3) δ: 2.55 (1H, s), 4.73 (2H, s), 6.81-6.83 (1H, m), 7.23-7.32 (2H, m), 7.49-7.53 (2H, m), 8.10-8.13 (2H, m), 8.19 (1H, d, J = 8.0 Hz), 8.24 (1H, d, J = 7.8 Hz), 8.38 (1H, s), 9.01 (1H, s). Production Example 40
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.20 g of 3-bromo-1-propyne and 5 ml of DMF, 0.55 g of cesium carbonate was added and stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 '-(2-propynyloxy) -quinoline-6- 0.28 g of carboxylic acid anilide (hereinafter referred to as the present compound 40) was obtained.
Compound 40 of the present invention
Figure JPOXMLDOC01-appb-C000050
 1 H-NMR (CDCl 3 ) δ: 2.55 (1H, s), 4.73 (2H, s), 6.81-6.83 (1H, m), 7.23-7.32 (2H, m), 7.49-7.53 (2H, m) , 8.10-8.13 (2H, m), 8.19 (1H, d, J = 8.0 Hz), 8.24 (1H, d, J = 7.8 Hz), 8.38 (1H, s), 9.01 (1H, s).
製造例４１
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、４－ブロモ－２－メチル－２－ブテン０．２２ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（３－メチル－２－ブテニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物４１と記す。）０．１０ｇを得た。
　本発明化合物４１
Figure JPOXMLDOC01-appb-C000051
 1H-NMR (CDCl3) δ: 1.76 (3H, s), 1.81 (3H, s), 4.56 (2H, d, J = 6.6 Hz), 5.51-5.54 (1H, m), 6.76 (1H, d, J = 7.8 Hz), 7.15 (1H, d, J = 8.0 Hz), 7.26-7.30 (1H, m), 7.49-7.52 (2H, m), 7.98 (1H, s), 8.14 (1H, d, J = 8.5 Hz), 8.21 (1H, d, J = 8.3 Hz), 8.28 (1H, d, J = 8.3 Hz), 8.39 (1H, s), 9.03 (1H, s). Production Example 41
To a mixture of 0.3 'g of 3'-hydroxy-quinoline-6-carboxylic acid anilide, 0.22 g of 4-bromo-2-methyl-2-butene and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. . Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, and dried under reduced pressure to give 3 ′-(3-methyl-2-butenyloxy) -quinoline. 0.10 g of -6-carboxylic acid anilide (hereinafter referred to as the present compound 41) was obtained.
Compound 41 of the present invention
Figure JPOXMLDOC01-appb-C000051
 1 H-NMR (CDCl 3 ) δ: 1.76 (3H, s), 1.81 (3H, s), 4.56 (2H, d, J = 6.6 Hz), 5.51-5.54 (1H, m), 6.76 (1H, d , J = 7.8 Hz), 7.15 (1H, d, J = 8.0 Hz), 7.26-7.30 (1H, m), 7.49-7.52 (2H, m), 7.98 (1H, s), 8.14 (1H, d, J = 8.5 Hz), 8.21 (1H, d, J = 8.3 Hz), 8.28 (1H, d, J = 8.3 Hz), 8.39 (1H, s), 9.03 (1H, s).
製造例４２
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、１－ブロモ－３－メチルブタン０．２１ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（３－メチル－２－ブトキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物４２と記す。）０．３３ｇを得た。
　本発明化合物４２
Figure JPOXMLDOC01-appb-C000052
 1H-NMR (CDCl3) δ: 0.98 (6H, d, J = 6.6 Hz), 1.67-1.72 (2H, m), 1.80-1.91 (1H, m), 4.04 (2H, t, J = 6.7 Hz), 6.74 (1H, dd, J = 8.3, 2.4 Hz), 7.13 (1H, d, J = 7.8 Hz), 7.25-7.30 (1H, m), 7.47 (1H, s), 7.51 (1H, dd, J = 8.3, 4.1 Hz), 7.94 (1H, s), 8.14 (1H, dd, J = 8.8, 2.0 Hz), 8.22 (1H, d, J = 8.8 Hz), 8.29 (1H, d, J = 7.8 Hz), 8.40 (1H, d, J = 2.0 Hz), 9.03 (1H, dd, J = 4.1, 1.7 Hz). Production Example 42
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.21 g of 1-bromo-3-methylbutane and 5 ml of DMF was added 0.55 g of cesium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, and dried under reduced pressure to give 3 ′-(3-methyl-2-butoxy) -quinoline. 0.33 g of -6-carboxylic acid anilide (hereinafter referred to as the present compound 42) was obtained.
Compound 42 of the present invention
Figure JPOXMLDOC01-appb-C000052
 1 H-NMR (CDCl 3 ) δ: 0.98 (6H, d, J = 6.6 Hz), 1.67-1.72 (2H, m), 1.80-1.91 (1H, m), 4.04 (2H, t, J = 6.7 Hz ), 6.74 (1H, dd, J = 8.3, 2.4 Hz), 7.13 (1H, d, J = 7.8 Hz), 7.25-7.30 (1H, m), 7.47 (1H, s), 7.51 (1H, dd, J = 8.3, 4.1 Hz), 7.94 (1H, s), 8.14 (1H, dd, J = 8.8, 2.0 Hz), 8.22 (1H, d, J = 8.8 Hz), 8.29 (1H, d, J = 7.8 Hz), 8.40 (1H, d, J = 2.0 Hz), 9.03 (1H, dd, J = 4.1, 1.7 Hz).
製造例４３
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、１－ブロモ－２－ペンチン０．２０ｇ及びＤＭＦ５ｍｌの混合物に、炭酸カリウム０．２４ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（２－ペンチニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物４３と記す。）０．２６ｇを得た。
　本発明化合物４３
Figure JPOXMLDOC01-appb-C000053
 1H-NMR (CDCl3) δ: 1.15 (3H, t, J = 7.4 Hz), 2.23-2.28 (2H, m), 4.71 (2H, s), 6.81 (1H, d, J = 7.6 Hz), 7.25-7.32 (2H, m), 7.46 (1H, s), 7.49 (1H, dd, J = 8.3, 4.1 Hz), 8.08 (1H, s), 8.13 (1H, d, J = 8.5 Hz), 8.19 (1H, d, J = 8.8 Hz), 8.26 (1H, d, J = 8.0 Hz), 8.40 (1H, s), 9.01 (1H, d, J = 2.7 Hz). Production Example 43
To a mixture of 0.3 'g of 3'-hydroxy-quinoline-6-carboxylic acid anilide, 0.20 g of 1-bromo-2-pentyne and 5 ml of DMF was added 0.24 g of potassium carbonate, and the mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 '-(2-pentynyloxy) -quinoline-6. -0.26 g of carboxylic acid anilide (hereinafter referred to as the present compound 43) was obtained.
Compound 43 of the present invention
Figure JPOXMLDOC01-appb-C000053
 1 H-NMR (CDCl 3 ) δ: 1.15 (3H, t, J = 7.4 Hz), 2.23-2.28 (2H, m), 4.71 (2H, s), 6.81 (1H, d, J = 7.6 Hz), 7.25-7.32 (2H, m), 7.46 (1H, s), 7.49 (1H, dd, J = 8.3, 4.1 Hz), 8.08 (1H, s), 8.13 (1H, d, J = 8.5 Hz), 8.19 (1H, d, J = 8.8 Hz), 8.26 (1H, d, J = 8.0 Hz), 8.40 (1H, s), 9.01 (1H, d, J = 2.7 Hz).
製造例４４
　３’－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、６－クロロ－１－ヘキシン０．１６ｇ及びＤＭＦ５ｍｌの混合物に、炭酸セシウム０．５５ｇを加え、室温で８時間攪拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して３’－（５－ヘキシニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物４４と記す。）０．３４ｇを得た。
　本発明化合物４４
Figure JPOXMLDOC01-appb-C000054
 1H-NMR (CDCl3) δ: 1.69-1.77 (2H, m), 1.88-1.98 (3H, m), 2.25-2.29 (2H, m), 3.98-4.01 (2H, m), 6.71 (1H, d, J = 7.6 Hz), 7.15 (1H, d, J = 7.3 Hz), 7.24 (1H, d, J = 8.0 Hz), 7.43-7.50 (2H, m), 8.09-8.17 (3H, m), 8.32-8.34 (2H, m), 8.97 (1H, s). Production Example 44
To a mixture of 0.30 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.16 g of 6-chloro-1-hexyne and 5 ml of DMF, 0.55 g of cesium carbonate was added and stirred at room temperature for 8 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, dried under reduced pressure, and 3 '-(5-hexynyloxy) -quinoline-6-carvone. 0.34 g of acid anilide (hereinafter referred to as the present compound 44) was obtained.
Compound 44 of the present invention
Figure JPOXMLDOC01-appb-C000054
 1 H-NMR (CDCl 3) δ: 1.69-1.77 (2H, m), 1.88-1.98 (3H, m), 2.25-2.29 (2H, m), 3.98-4.01 (2H, m), 6.71 (1H, d, J = 7.6 Hz), 7.15 (1H, d, J = 7.3 Hz), 7.24 (1H, d, J = 8.0 Hz), 7.43-7.50 (2H, m), 8.09-8.17 (3H, m), 8.32-8.34 (2H, m), 8.97 (1H, s).
製造例４５
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、１－ヨードペンタン０．２３ｇ及び炭酸セシウム０．４５ｇをＤＭＦ２ｍｌに加え、室温で２０時間攪拌した。反応混合物に水を加えて、酢酸エチルで抽出した後、飽和炭酸水素ナトリウム水溶液で洗浄した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２’－フルオロ－３’－ペンチルオキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物４５と記す。）１８９ｍｇを得た。
　本発明化合物４５
Figure JPOXMLDOC01-appb-C000055
 1H -NMR (CDCl3) δ: 0.95 (3H, t, J = 7.0 Hz), 1.37-1.51 (4H, m), 1.81-1.88 (2H, m), 4.07 (2H, t, J = 6.6 Hz), 6.79 (1H, t, J = 8.3 Hz), 7.12 (1H, t, J = 8.3 Hz), 7.52 (1H, dd, J = 8.3, 4.1 Hz), 8.07 (1H, t, J = 7.3 Hz), 8.16-8.33 (4H, m), 8.42 (1H, s), 9.04 (1H, d, J = 4.1 Hz). Production Example 45
2'-Fluoro-3'-hydroxy-quinoline-6-carboxylic acid anilide (0.30 g), 1-iodopentane (0.23 g) and cesium carbonate (0.45 g) were added to DMF (2 ml), and the mixture was stirred at room temperature for 20 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 189 mg of 2′-fluoro-3′-pentyloxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 45).
Compound 45 of the present invention
Figure JPOXMLDOC01-appb-C000055
 1 H -NMR (CDCl 3 ) δ: 0.95 (3H, t, J = 7.0 Hz), 1.37-1.51 (4H, m), 1.81-1.88 (2H, m), 4.07 (2H, t, J = 6.6 Hz ), 6.79 (1H, t, J = 8.3 Hz), 7.12 (1H, t, J = 8.3 Hz), 7.52 (1H, dd, J = 8.3, 4.1 Hz), 8.07 (1H, t, J = 7.3 Hz) ), 8.16-8.33 (4H, m), 8.42 (1H, s), 9.04 (1H, d, J = 4.1 Hz).
製造例４６
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド０．３０ｇ、１－ブロモヘキサン０．１９ｇ及び炭酸セシウム０．４５ｇをＤＭＦ２ｍｌに加え、室温で２０時間攪拌した。反応混合物に水を加えて、酢酸エチルで抽出した後、飽和炭酸水素ナトリウム水溶液で洗浄した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２’－フルオロ－３’－ヘキシルオキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物４６と記す。）１０７ｍｇを得た。
　本発明化合物４６
Figure JPOXMLDOC01-appb-C000056
 1H-NMR (CDCl3) δ: 0.92 (3H, t, J = 7.1 Hz), 1.33-1.39 (4H, m), 1.45-1.51 (2H, m), 1.80-1.87 (2H, m), 4.07 (2H, t, J = 6.6 Hz), 6.79 (1H, td, J = 8.3, 1.5 Hz), 7.11 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.4 Hz), 8.05-8.10 (1H, m), 8.16-8.25 (3H, m), 8.31 (1H, dd, J = 8.4, 1.1 Hz), 8.42 (1H, d, J = 2.0 Hz), 9.03 (1H, dd, J = 4.4, 1.7 Hz). Production Example 46
0.30 g of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.19 g of 1-bromohexane and 0.45 g of cesium carbonate were added to 2 ml of DMF, and the mixture was stirred at room temperature for 20 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 107 mg of 2′-fluoro-3′-hexyloxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 46).
Compound 46 of the present invention
Figure JPOXMLDOC01-appb-C000056
 1 H-NMR (CDCl 3 ) δ: 0.92 (3H, t, J = 7.1 Hz), 1.33-1.39 (4H, m), 1.45-1.51 (2H, m), 1.80-1.87 (2H, m), 4.07 (2H, t, J = 6.6 Hz), 6.79 (1H, td, J = 8.3, 1.5 Hz), 7.11 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.4 Hz), 8.05-8.10 (1H, m), 8.16-8.25 (3H, m), 8.31 (1H, dd, J = 8.4, 1.1 Hz), 8.42 (1H, d, J = 2.0 Hz), 9.03 (1H , dd, J = 4.4, 1.7 Hz).
製造例４７
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド０．２８ｇ、４－ブロモ－１－ペンテン０．１５ｇ及び炭酸セシウム０．４２ｇをＤＭＦ２ｍｌに加え、室温で５時間攪拌した。反応混合物に水を加えて、酢酸エチルで抽出した後、飽和食塩水で洗浄した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２’－フルオロ－３’－（４－ペンテニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物４７と記す。）２１５ｍｇを得た。
　本発明化合物４７
Figure JPOXMLDOC01-appb-C000057
 1H-NMR (CDCl3) δ: 1.91-1.98 (2H, m), 2.25-2.31 (2H, m), 4.08 (2H, t, J = 6.5 Hz), 5.01-5.11 (2H, m), 5.81-5.93 (1H, m), 6.77-6.82 (1H, m), 7.09-7.13 (1H, m), 7.52 (1H, dd, J = 8.2, 4.3 Hz), 8.06-8.33 (5H, m), 8.42-8.44 (1H, m), 9.03-9.05 (1H, m). Production Example 47
0.28 g of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.15 g of 4-bromo-1-pentene and 0.42 g of cesium carbonate were added to 2 ml of DMF, and the mixture was stirred at room temperature for 5 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 215 mg of 2′-fluoro-3 ′-(4-pentenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 47). .
Compound 47 of the present invention
Figure JPOXMLDOC01-appb-C000057
 1 H-NMR (CDCl 3 ) δ: 1.91-1.98 (2H, m), 2.25-2.31 (2H, m), 4.08 (2H, t, J = 6.5 Hz), 5.01-5.11 (2H, m), 5.81 -5.93 (1H, m), 6.77-6.82 (1H, m), 7.09-7.13 (1H, m), 7.52 (1H, dd, J = 8.2, 4.3 Hz), 8.06-8.33 (5H, m), 8.42 -8.44 (1H, m), 9.03-9.05 (1H, m).
製造例４８
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド０．２８ｇ、６－ブロモ－１－ヘキセン０．１６ｇ及び炭酸セシウム０．４２ｇをＤＭＦ２ｍｌに加え、室温で５時間攪拌した。反応混合物に水を加えて、酢酸エチルで抽出した後、飽和炭酸水素ナトリウム水溶液で洗浄した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２’－フルオロ－３’－（５－ヘキセニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物４８と記す。）２５２ｍｇを得た。
　本発明化合物４８
Figure JPOXMLDOC01-appb-C000058
 1H-NMR (CDCl3) δ: 1.56-1.64 (2H, m), 1.83-1.90 (2H, m), 2.12-2.19 (2H, m), 4.08 (2H, t, J = 6.5 Hz), 4.97-5.09 (2H, m), 5.79-5.89 (1H, m), 6.79 (1H, td, J = 8.3, 1.2 Hz), 7.11 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.1 Hz), 8.08 (1H, t, J = 7.0 Hz), 8.16-8.26 (3H, m), 8.31 (1H, d, J = 8.3 Hz), 8.42 (1H, d, J = 1.7 Hz), 9.04 (1H, dd, J = 4.1, 1.7 Hz). Production Example 48
0.28 g of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.16 g of 6-bromo-1-hexene and 0.42 g of cesium carbonate were added to 2 ml of DMF, and the mixture was stirred at room temperature for 5 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 252 mg of 2′-fluoro-3 ′-(5-hexenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 48). .
Compound 48 of the present invention
Figure JPOXMLDOC01-appb-C000058
 1 H-NMR (CDCl 3 ) δ: 1.56-1.64 (2H, m), 1.83-1.90 (2H, m), 2.12-2.19 (2H, m), 4.08 (2H, t, J = 6.5 Hz), 4.97 -5.09 (2H, m), 5.79-5.89 (1H, m), 6.79 (1H, td, J = 8.3, 1.2 Hz), 7.11 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd , J = 8.3, 4.1 Hz), 8.08 (1H, t, J = 7.0 Hz), 8.16-8.26 (3H, m), 8.31 (1H, d, J = 8.3 Hz), 8.42 (1H, d, J = 1.7 Hz), 9.04 (1H, dd, J = 4.1, 1.7 Hz).
製造例４９
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド０．２８ｇ、６－ブロモ－１－ヘキシン０．１８ｇ及び炭酸セシウム０．４２ｇをＤＭＦ２ｍｌに加え、室温で２０時間攪拌した。反応混合物に水を加えて、酢酸エチルで抽出した後、飽和炭酸水素ナトリウム水溶液で洗浄した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２’－フルオロ－３’－（５－ヘキシニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物４９と記す。）２０５ｍｇを得た。
　本発明化合物４９
Figure JPOXMLDOC01-appb-C000059
 1H-NMR (CDCl3) δ: 1.72-1.80 (2H, m), 1.93-2.01 (3H, m), 2.31 (2H, td, J = 7.0, 2.5 Hz), 4.10 (2H, t, J = 6.2 Hz), 6.79 (1H, td, J = 8.2, 1.3 Hz), 7.11 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.1 Hz), 8.05-8.09 (1H, m), 8.15-8.25 (3H, m), 8.30 (1H, dd, J = 8.4, 1.1 Hz), 8.41 (1H, d, J = 2.0 Hz), 9.03 (1H, dd, J = 4.4, 1.7 Hz). Production Example 49
0.28 g of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 0.18 g of 6-bromo-1-hexyne and 0.42 g of cesium carbonate were added to 2 ml of DMF, and the mixture was stirred at room temperature for 20 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and washed with a saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 205 mg of 2′-fluoro-3 ′-(5-hexynyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 49).
Compound 49 of the present invention
Figure JPOXMLDOC01-appb-C000059
 1 H-NMR (CDCl 3 ) δ: 1.72-1.80 (2H, m), 1.93-2.01 (3H, m), 2.31 (2H, td, J = 7.0, 2.5 Hz), 4.10 (2H, t, J = 6.2 Hz), 6.79 (1H, td, J = 8.2, 1.3 Hz), 7.11 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.1 Hz), 8.05-8.09 ( 1H, m), 8.15-8.25 (3H, m), 8.30 (1H, dd, J = 8.4, 1.1 Hz), 8.41 (1H, d, J = 2.0 Hz), 9.03 (1H, dd, J = 4.4, 1.7 Hz).
製造例５０
　２－フルオロ－３－メトキシアニリン０．１６ｇ、［１，５］ナフチリジン－２－カルボン酸０．２０ｇ、ＷＳＣ０．２９ｇ及びピリジン３ｍｌの混合物を室温で４時間撹拌した。反応混合物に水を加え、析出した固体を濾集し、３％水酸化ナトリウム水溶液、水及びヘキサンで順次洗浄し、減圧下で乾燥して２’－フルオロ－３’－メトキシ－[１，５]－ナフチリジン－２－カルボン酸アニリド（以下、本発明化合物５０と記す。）０．２７ｇを得た。
　本発明化合物５０
Figure JPOXMLDOC01-appb-C000060
 1H-NMR (CDCl3) δ: 3.94 (3H, s), 6.78-6.82 (1H, m), 7.12-7.17 (1H, m), 7.75-7.77 (1H, m), 8.18-8.22 (1H, m), 8.53 (1H, d, J = 8.5 Hz), 8.62 (2H, s), 9.10 (1H, s), 10.45 (1H, s). Production Example 50
A mixture of 0.16 g of 2-fluoro-3-methoxyaniline, 0.20 g of [1,5] naphthyridine-2-carboxylic acid, 0.29 g of WSC and 3 ml of pyridine was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the precipitated solid was collected by filtration, washed successively with 3% aqueous sodium hydroxide solution, water and hexane, and dried under reduced pressure to give 2'-fluoro-3'-methoxy- [1,5 ] -Naphthyridine-2-carboxylic acid anilide (hereinafter referred to as the present compound 50) 0.27 g was obtained.
Compound 50 of the present invention
Figure JPOXMLDOC01-appb-C000060
 1 H-NMR (CDCl 3 ) δ: 3.94 (3H, s), 6.78-6.82 (1H, m), 7.12-7.17 (1H, m), 7.75-7.77 (1H, m), 8.18-8.22 (1H, m), 8.53 (1H, d, J = 8.5 Hz), 8.62 (2H, s), 9.10 (1H, s), 10.45 (1H, s).
製造例５１
　ベンゾチアゾール－６－カルボン酸塩化物０．２０ｇ、２－フルオロ－３－メトキシアニリン０．１５ｇ及びトリエチルアミン０．２０ｇをクロロホルム１ｍｌに加え、室温で４時間攪拌した。反応混合物をシリカゲルカラムクロマトグラフィーに付して２’－フルオロ－３’－メトキシ－ベンゾチアゾール－６－カルボン酸アニリド（以下、本発明化合物５１と記す。）０．２７ｇを得た。
本発明化合物５１
Figure JPOXMLDOC01-appb-C000061
 1H -NMR (CDCl3) δ: 3.93 (3H, s), 6.77-6.82 (1H, m), 7.10-7.16 (1H, m), 8.01 (1H, dd, J = 8.7, 1.4 Hz), 8.04-8.09 (1H, m), 8.14 (1H, br s), 8.25 (1H, d, J = 8.7 Hz), 8.59 (1H, d, J = 1.4 Hz), 9.17 (1H, s). Production Example 51
0.20 g of benzothiazole-6-carboxylic acid chloride, 0.15 g of 2-fluoro-3-methoxyaniline and 0.20 g of triethylamine were added to 1 ml of chloroform, followed by stirring at room temperature for 4 hours. The reaction mixture was subjected to silica gel column chromatography to obtain 0.27 g of 2′-fluoro-3′-methoxy-benzothiazole-6-carboxylic acid anilide (hereinafter referred to as the present compound 51).
Compound 51 of the present invention
Figure JPOXMLDOC01-appb-C000061
 1 H -NMR (CDCl 3 ) δ: 3.93 (3H, s), 6.77-6.82 (1H, m), 7.10-7.16 (1H, m), 8.01 (1H, dd, J = 8.7, 1.4 Hz), 8.04 -8.09 (1H, m), 8.14 (1H, br s), 8.25 (1H, d, J = 8.7 Hz), 8.59 (1H, d, J = 1.4 Hz), 9.17 (1H, s).
製造例５２
　ベンゾチアゾール－６－カルボン酸塩化物２００ｍｇ、４－メチルアニリン２６８ｍｇ及びトリエチルアミン１１１ｍｇをＴＨＦ２ｍｌに加え、室温で１時間攪拌した。反応混合物に飽和食塩水を加え、酢酸エチルで抽出した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して４’－メチル－ベンゾチアゾール－６－カルボン酸アニリド（以下、本発明化合物５２と記す。）１００ｍｇを得た。
　本発明化合物５２
Figure JPOXMLDOC01-appb-C000062
 1H-NMR (CDCl3) δ: 2.36 (3H, s), 7.20 (2H, d, J = 8.3 Hz), 7.54 (2H, d, J = 8.3 Hz), 7.87 (1H, br s), 7.97 (1H, dd, J = 8.6, 1.5 Hz), 8.22 (1H, d, J = 8.6 Hz), 8.56 (1H, d, J = 1.5 Hz), 9.14 (1H, s). Production Example 52
200 mg of benzothiazole-6-carboxylic acid chloride, 268 mg of 4-methylaniline and 111 mg of triethylamine were added to 2 ml of THF, and the mixture was stirred at room temperature for 1 hour. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 100 mg of 4′-methyl-benzothiazole-6-carboxylic acid anilide (hereinafter referred to as the present compound 52).
Compound 52 of the present invention
Figure JPOXMLDOC01-appb-C000062
 1 H-NMR (CDCl 3 ) δ: 2.36 (3H, s), 7.20 (2H, d, J = 8.3 Hz), 7.54 (2H, d, J = 8.3 Hz), 7.87 (1H, br s), 7.97 (1H, dd, J = 8.6, 1.5 Hz), 8.22 (1H, d, J = 8.6 Hz), 8.56 (1H, d, J = 1.5 Hz), 9.14 (1H, s).
製造例５３
　ベンゾチアゾール－６－カルボン酸塩化物２００ｍｇ、３－フェノキシアニリン１８５ｍｇ及びトリエチルアミン１１１ｍｇをＴＨＦ２ｍｌに加え、室温で１時間攪拌した。反応混合物に飽和食塩水を加え、酢酸エチルで抽出した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して３’－フェノキシ－ベンゾチアゾール－６－カルボン酸アニリド（以下、本発明化合物５３と記す。）１７９ｍｇを得た。
　本発明化合物５３
Figure JPOXMLDOC01-appb-C000063
 1H-NMR (CDCl3) δ: 6.83 (1H, ddd, J = 8.1, 2.2, 1.1 Hz), 7.04-7.08 (2H, m), 7.11-7.16 (1H, m), 7.32-7.38 (4H, m), 7.41-7.44 (1H, m), 7.89 (1H, br s), 7.95 (1H, dd, J = 8.3, 1.5 Hz), 8.21 (1H, d, J = 8.3 Hz), 8.54 (1H, d, J = 1.5 Hz), 9.15 (1H, s). Production Example 53
200 mg of benzothiazole-6-carboxylic acid chloride, 185 mg of 3-phenoxyaniline and 111 mg of triethylamine were added to 2 ml of THF, followed by stirring at room temperature for 1 hour. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 179 mg of 3′-phenoxy-benzothiazole-6-carboxylic acid anilide (hereinafter referred to as the present compound 53).
Compound 53 of the present invention
Figure JPOXMLDOC01-appb-C000063
 1 H-NMR (CDCl 3 ) δ: 6.83 (1H, ddd, J = 8.1, 2.2, 1.1 Hz), 7.04-7.08 (2H, m), 7.11-7.16 (1H, m), 7.32-7.38 (4H, m), 7.41-7.44 (1H, m), 7.89 (1H, br s), 7.95 (1H, dd, J = 8.3, 1.5 Hz), 8.21 (1H, d, J = 8.3 Hz), 8.54 (1H, d, J = 1.5 Hz), 9.15 (1H, s).
製造例５４
　ベンゾチアゾール－６－カルボン酸塩化物２００ｍｇ、３－メトキシアニリン１２３ｍｇ及びトリエチルアミン１１１ｍｇをＴＨＦ２ｍｌに加え、室温で１時間攪拌した。反応混合物に飽和食塩水を加え、酢酸エチルで抽出した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して３’－メトキシ－ベンゾチアゾール－６－カルボン酸アニリド（以下、本発明化合物５４と記す。）１１４ｍｇを得た。
　本発明化合物５４
Figure JPOXMLDOC01-appb-C000064
 1H-NMR (CDCl3) δ: 3.85 (3H, s), 6.74 (1H, dd, J = 8.2, 1.9 Hz), 7.13 (1H, dd, J = 8.0, 2.2 Hz), 7.29 (1H, dd, J = 8.2, 8.0 Hz), 7.45 (1H, dd, J = 2.2, 1.9 Hz), 7.89 (1H, br s), 7.98 (1H, dd, J = 8.6, 1.8 Hz), 8.23 (1H, d, J = 8.6 Hz), 8.57 (1H, d, J = 1.8 Hz), 9.15 (1H, s). Production Example 54
200 mg of benzothiazole-6-carboxylic acid chloride, 123 mg of 3-methoxyaniline and 111 mg of triethylamine were added to 2 ml of THF, and the mixture was stirred at room temperature for 1 hour. Saturated brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 114 mg of 3′-methoxy-benzothiazole-6-carboxylic acid anilide (hereinafter referred to as the present compound 54).
Compound 54 of the present invention
Figure JPOXMLDOC01-appb-C000064
 1 H-NMR (CDCl 3 ) δ: 3.85 (3H, s), 6.74 (1H, dd, J = 8.2, 1.9 Hz), 7.13 (1H, dd, J = 8.0, 2.2 Hz), 7.29 (1H, dd , J = 8.2, 8.0 Hz), 7.45 (1H, dd, J = 2.2, 1.9 Hz), 7.89 (1H, br s), 7.98 (1H, dd, J = 8.6, 1.8 Hz), 8.23 (1H, d , J = 8.6 Hz), 8.57 (1H, d, J = 1.8 Hz), 9.15 (1H, s).
製造例５５
　[１，５]－ナフチリジン－２－カルボン酸３４８ｍｇ、４－ブチルアニリン２９８ｍｇ、ＢＯＰ試薬８８４ｍｇ及びトリエチルアミン１．０ｇをＤＭＦ１ｍｌに加え、室温で３時間攪拌した後、一晩放置した。反応混合物に酢酸エチルを加え、水及び飽和炭酸水素ナトリウム水溶液で順次洗浄した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して４’－ブチル－[１，５]－ナフチリジン－２－カルボン酸アニリド（以下、本発明化合物５５と記す。）１５５ｍｇを得た。
　本発明化合物５５
Figure JPOXMLDOC01-appb-C000065
 1H-NMR (CDCl3) δ: 0.94 (3H, t, J = 7.5 Hz), 1.33-1.42 (2H, m), 1.58-1.66 (2H, m), 2.63 (2H, t, J = 7.7 Hz), 7.24 (2H, d, J = 8.6 Hz), 7.72-7.76 (3H, m), 8.50 (1H, ddd, J = 8.6, 1.6, 0.8 Hz), 8.60 (1H, dd, J = 8.7, 0.8 Hz), 8.65 (1H, d, J = 8.8 Hz), 9.09 (1H, dd, J = 4.2, 1.6 Hz), 10.06 (1H, br s). Production Example 55
348 mg of [1,5] -naphthyridine-2-carboxylic acid, 298 mg of 4-butylaniline, 884 mg of BOP reagent and 1.0 g of triethylamine were added to 1 ml of DMF, stirred at room temperature for 3 hours, and then left overnight. Ethyl acetate was added to the reaction mixture, and the mixture was washed successively with water and saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 155 mg of 4′-butyl- [1,5] -naphthyridine-2-carboxylic acid anilide (hereinafter referred to as the present compound 55).
Compound 55 of the present invention
Figure JPOXMLDOC01-appb-C000065
 1 H-NMR (CDCl 3 ) δ: 0.94 (3H, t, J = 7.5 Hz), 1.33-1.42 (2H, m), 1.58-1.66 (2H, m), 2.63 (2H, t, J = 7.7 Hz ), 7.24 (2H, d, J = 8.6 Hz), 7.72-7.76 (3H, m), 8.50 (1H, ddd, J = 8.6, 1.6, 0.8 Hz), 8.60 (1H, dd, J = 8.7, 0.8 Hz), 8.65 (1H, d, J = 8.8 Hz), 9.09 (1H, dd, J = 4.2, 1.6 Hz), 10.06 (1H, br s).
製造例５６
　[１，５]－ナフチリジン－６－カルボン酸３４８ｍｇ、３－メチルアニリン２１４ｍｇ、ＢＯＰ試薬８８４ｍｇ及びトリエチルアミン１．０ｇをＤＭＦ１ｍｌに加え、室温で３時間攪拌した後、一晩放置した。反応混合物に酢酸エチルを加え、水及び飽和炭酸水素ナトリウム水溶液で順次洗浄した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して３’－メチル－[１，５]－ナフチリジン－２－カルボン酸アニリド（以下、本発明化合物５６と記す。）２１４ｍｇを得た。
　本発明化合物５６
Figure JPOXMLDOC01-appb-C000066
 1H-NMR (CDCl3) δ: 2.42 (3H, s), 7.01 (1H, d, J = 7.7 Hz), 7.29-7.34 (1H, m), 7.62-7.66 (1H, m), 7.70-7.72 (1H, m), 7.75 (1H, dd, J = 8.5, 4.2 Hz), 8.50 (1H, ddd, J = 8.6, 1.6, 0.8 Hz), 8.61 (1H, dd, J = 8.7, 0.8 Hz), 8.65 (1H, d, J = 8.6 Hz), 9.09 (1H, dd, J = 4.2, 1.6 Hz), 10.07 (1H, br s). Production Example 56
348 mg of [1,5] -naphthyridine-6-carboxylic acid, 214 mg of 3-methylaniline, 884 mg of BOP reagent and 1.0 g of triethylamine were added to 1 ml of DMF, stirred at room temperature for 3 hours, and then left overnight. Ethyl acetate was added to the reaction mixture, and the mixture was washed successively with water and saturated aqueous sodium hydrogen carbonate solution. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 214 mg of 3′-methyl- [1,5] -naphthyridine-2-carboxylic acid anilide (hereinafter referred to as the present compound 56).
Compound 56 of the present invention
Figure JPOXMLDOC01-appb-C000066
 1 H-NMR (CDCl 3 ) δ: 2.42 (3H, s), 7.01 (1H, d, J = 7.7 Hz), 7.29-7.34 (1H, m), 7.62-7.66 (1H, m), 7.70-7.72 (1H, m), 7.75 (1H, dd, J = 8.5, 4.2 Hz), 8.50 (1H, ddd, J = 8.6, 1.6, 0.8 Hz), 8.61 (1H, dd, J = 8.7, 0.8 Hz), 8.65 (1H, d, J = 8.6 Hz), 9.09 (1H, dd, J = 4.2, 1.6 Hz), 10.07 (1H, br s).
製造例５７
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２９５ｍｇ、１－ブロモ－３－メトキシープロパン１７６ｍｇ及び炭酸セシウム４０９ｍｇをＤＭＦ４ｍｌに加え、室温で３時間攪拌した。反応混合物に水を加えてから氷冷した後、析出した固体をろ過し、へキサンで洗浄した。得られた固体を減圧下乾燥し、２'－フルオロ－３'－（３－メトキシプロピルオキシ）キノリン－６－カルボン酸アニリド（以下、本発明化合物５７と記す。）３２８ｍｇを得た。
　本発明化合物５７
Figure JPOXMLDOC01-appb-C000067
 1H-NMR (CDCl3) δ: 2.07-2.13 (2H, m), 3.37 (3H, s), 3.59 (2H, t, J = 6.0 Hz), 4.17 (2H, t, J = 6.3 Hz), 6.80-6.84 (1H, m), 7.11 (1H, td, J = 8.5, 1.9 Hz), 7.52 (1H, dd, J = 8.3, 4.2 Hz), 8.07 (1H, t, J = 7.0 Hz), 8.20-8.27 (4H, m), 8.42 (1H, d, J = 1.7 Hz), 9.03 (1H, dd, J = 4.1, 1.7 Hz). Production Example 57
295 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 176 mg of 1-bromo-3-methoxypropane, and 409 mg of cesium carbonate were added to 4 ml of DMF, and the mixture was stirred at room temperature for 3 hours. After adding water to the reaction mixture and cooling with ice, the precipitated solid was filtered and washed with hexane. The obtained solid was dried under reduced pressure to obtain 328 mg of 2′-fluoro-3 ′-(3-methoxypropyloxy) quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 57).
Compound 57 of the present invention
Figure JPOXMLDOC01-appb-C000067
 1 H-NMR (CDCl 3 ) δ: 2.07-2.13 (2H, m), 3.37 (3H, s), 3.59 (2H, t, J = 6.0 Hz), 4.17 (2H, t, J = 6.3 Hz), 6.80-6.84 (1H, m), 7.11 (1H, td, J = 8.5, 1.9 Hz), 7.52 (1H, dd, J = 8.3, 4.2 Hz), 8.07 (1H, t, J = 7.0 Hz), 8.20 -8.27 (4H, m), 8.42 (1H, d, J = 1.7 Hz), 9.03 (1H, dd, J = 4.1, 1.7 Hz).
製造例５８
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２８６ｍｇ、４－クロロ－２－メチル－２－ブテン１１６ｍｇ及び炭酸セシウム３９６ｍｇをＤＭＦ５ｍｌに加え、室温で６時間３０分間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えて、酢酸エチルで抽出した後、飽和食塩水で洗浄した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－（３－メチル－２－ブテニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物５８と記す。）２５１ｍｇを得た。
　本発明化合物５８
Figure JPOXMLDOC01-appb-C000068
 1H-NMR (CDCl3) δ: 1.75 (3H, s), 1.80 (3H, s), 4.61 (2H, d, J = 6.8 Hz), 5.50-5.52 (1H, m), 6.80 (1H, td, J = 8.2, 1.2 Hz), 7.09 (1H, td, J = 8.3, 1.9 Hz), 7.49 (1H, dd, J = 8.3, 4.2 Hz), 8.02-8.06 (1H, m), 8.15-8.29 (4H, m), 8.40 (1H, d, J = 1.7 Hz), 9.01 (1H, dd, J = 4.2, 1.6 Hz). Production Example 58
286 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 116 mg of 4-chloro-2-methyl-2-butene and 396 mg of cesium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 6 hours and 30 minutes. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and 251 mg of 2'-fluoro-3 '-(3-methyl-2-butenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 58). Got.
Compound 58 of the present invention
Figure JPOXMLDOC01-appb-C000068
 1 H-NMR (CDCl 3 ) δ: 1.75 (3H, s), 1.80 (3H, s), 4.61 (2H, d, J = 6.8 Hz), 5.50-5.52 (1H, m), 6.80 (1H, td , J = 8.2, 1.2 Hz), 7.09 (1H, td, J = 8.3, 1.9 Hz), 7.49 (1H, dd, J = 8.3, 4.2 Hz), 8.02-8.06 (1H, m), 8.15-8.29 ( 4H, m), 8.40 (1H, d, J = 1.7 Hz), 9.01 (1H, dd, J = 4.2, 1.6 Hz).
製造例５９
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２９３ｍｇ、１－ブロモ－２－メチルプロパン１５６ｍｇ及び炭酸セシウム４０６ｍｇをＤＭＦ５ｍｌに加え、室温で１４時間３０分間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えて、酢酸エチルで抽出した後、飽和食塩水で洗浄した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－（２－メチル－プロピルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物５９と記す。）２５２ｍｇを得た。
　本発明化合物５９
Figure JPOXMLDOC01-appb-C000069
 1H-NMR (CDCl3) δ: 1.05 (3H, s), 1.06 (3H, s), 2.11-2.18 (1H, m), 3.83 (2H, d, J = 6.6 Hz), 6.78 (1H, t, J = 7.9 Hz), 7.10 (1H, t, J = 7.6 Hz), 7.51 (1H, dd, J = 8.3, 4.4 Hz), 8.06 (1H, t, J = 7.1 Hz), 8.20-8.27 (4H, m), 8.41 (1H, s), 9.03 (1H, d, J = 2.7 Hz). Production Example 59
293 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 156 mg of 1-bromo-2-methylpropane and 406 mg of cesium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 14 hours and 30 minutes. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, and 252 mg of 2′-fluoro-3 ′-(2-methyl-propyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 59) was obtained. Obtained.
Compound 59 of the present invention
Figure JPOXMLDOC01-appb-C000069
 1 H-NMR (CDCl 3 ) δ: 1.05 (3H, s), 1.06 (3H, s), 2.11-2.18 (1H, m), 3.83 (2H, d, J = 6.6 Hz), 6.78 (1H, t , J = 7.9 Hz), 7.10 (1H, t, J = 7.6 Hz), 7.51 (1H, dd, J = 8.3, 4.4 Hz), 8.06 (1H, t, J = 7.1 Hz), 8.20-8.27 (4H , m), 8.41 (1H, s), 9.03 (1H, d, J = 2.7 Hz).
製造例６０
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２９７ｍｇ、ブロモメチルシクロプロパン１５６ｍｇ及び炭酸セシウム４１１ｍｇをＤＭＦ４ｍｌに加え、室温で９時間攪拌した。反応混合物に水を加えてから氷冷した後、析出した固体をろ過し、へキサンで洗浄した。得られた固体を減圧下乾燥し、２'－フルオロ－３'－シクロプロピルメチルオキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物６０と記す。）２５４ｍｇを得た。
　本発明化合物６０
Figure JPOXMLDOC01-appb-C000070
 1H-NMR (CDCl3) δ: 0.38 (2H, d, J = 4.9 Hz), 0.66 (2H, dd, J = 12.7, 5.4 Hz), 1.30-1.32 (1H, m), 3.91 (2H, d, J = 6.8 Hz), 6.77 (1H, t, J = 7.9 Hz), 7.09 (1H, t, J = 7.6 Hz), 7.51 (1H, dd, J = 8.2, 4.3 Hz), 8.14-8.31 (6H, m), 9.02 (1H, d, J = 2.7 Hz). Production Example 60
297 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 156 mg of bromomethylcyclopropane and 411 mg of cesium carbonate were added to 4 ml of DMF, and the mixture was stirred at room temperature for 9 hours. After adding water to the reaction mixture and cooling with ice, the precipitated solid was filtered and washed with hexane. The obtained solid was dried under reduced pressure to obtain 254 mg of 2′-fluoro-3′-cyclopropylmethyloxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 60).
Compound 60 of the present invention
Figure JPOXMLDOC01-appb-C000070
 1 H-NMR (CDCl 3 ) δ: 0.38 (2H, d, J = 4.9 Hz), 0.66 (2H, dd, J = 12.7, 5.4 Hz), 1.30-1.32 (1H, m), 3.91 (2H, d , J = 6.8 Hz), 6.77 (1H, t, J = 7.9 Hz), 7.09 (1H, t, J = 7.6 Hz), 7.51 (1H, dd, J = 8.2, 4.3 Hz), 8.14-8.31 (6H , m), 9.02 (1H, d, J = 2.7 Hz).
製造例６１
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２７３ｍｇ、１－ブロモー２－ブチン１４１ｍｇ及び炭酸セシウム３７８ｍｇをＤＭＦ５ｍｌに加え、室温で３０分間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えて、酢酸エチルで抽出した後、飽和食塩水で洗浄した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた固体をへキサンで洗浄後、減圧下乾燥し２'－フルオロ－３'－（２－ブチニルオキシ）キノリン－６－カルボン酸アニリド（以下、本発明化合物６１と記す。）２８２ｍｇを得た。
　本発明化合物６１
Figure JPOXMLDOC01-appb-C000071
 1H -NMR (CDCl3) δ: 1.87 (3H, s), 4.76 (2H, d, J = 6.6 Hz), 6.92 (1H, td, J = 8.2, 1.3 Hz), 7.13 (1H, td, J = 8.4, 1.9 Hz), 7.51 (1H, dd, J = 8.3, 4.4 Hz), 8.10-8.31 (5H, m), 8.41 (1H, d, J = 1.7 Hz), 9.03 (1H, dd, J = 4.1, 1.7 Hz). Production Example 61
273 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 141 mg of 1-bromo-2-butyne and 378 mg of cesium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained solid was washed with hexane and dried under reduced pressure to obtain 282 mg of 2′-fluoro-3 ′-(2-butynyloxy) quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 61). .
Compound 61 of the present invention
Figure JPOXMLDOC01-appb-C000071
 1 H -NMR (CDCl 3 ) δ: 1.87 (3H, s), 4.76 (2H, d, J = 6.6 Hz), 6.92 (1H, td, J = 8.2, 1.3 Hz), 7.13 (1H, td, J = 8.4, 1.9 Hz), 7.51 (1H, dd, J = 8.3, 4.4 Hz), 8.10-8.31 (5H, m), 8.41 (1H, d, J = 1.7 Hz), 9.03 (1H, dd, J = 4.1, 1.7 Hz).
製造例６２
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２９０ｍｇ、１－ブロモ－２－ペンチン１６７ｍｇ及び炭酸セシウム４０２ｍｇをＤＭＦ５ｍｌに加え、室温で１０分間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えて、酢酸エチルで抽出した後、飽和食塩水で洗浄した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－（２－ペンチニル）オキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物６２と記す。）２９８ｍｇを得た。
　本発明化合物６２
Figure JPOXMLDOC01-appb-C000072
 1H-NMR (CDCl3) δ: 1.14 (3H, t, J = 7.6 Hz), 2.21-2.27 (2H, m), 4.78 (2H, d, J = 2.1 Hz), 6.93 (1H, td, J = 8.2, 1.1 Hz), 7.14 (1H, td, J = 8.3, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.1 Hz), 8.16-8.27 (5H, m), 8.42 (1H, d, J = 1.7 Hz), 9.03 (1H, dd, J = 4.3, 1.6 Hz). Production Example 62
290 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 167 mg of 1-bromo-2-pentyne and 402 mg of cesium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 10 minutes. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 298 mg of 2′-fluoro-3 ′-(2-pentynyl) oxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 62). .
Compound 62 of the present invention
Figure JPOXMLDOC01-appb-C000072
 1 H-NMR (CDCl 3 ) δ: 1.14 (3H, t, J = 7.6 Hz), 2.21-2.27 (2H, m), 4.78 (2H, d, J = 2.1 Hz), 6.93 (1H, td, J = 8.2, 1.1 Hz), 7.14 (1H, td, J = 8.3, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.1 Hz), 8.16-8.27 (5H, m), 8.42 (1H, d, J = 1.7 Hz), 9.03 (1H, dd, J = 4.3, 1.6 Hz).
製造例６３
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド３２３ｍｇ、ブロモプロパン１５５ｍｇ及び炭酸セシウム４４７ｍｇをＤＭＦ５ｍｌに加え、室温で４時間３０分間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えてから氷冷した後、析出した固体をろ過し、へキサンで洗浄した。得られた固体を減圧下乾燥し、２'－フルオロ－３'－プロポキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物６３と記す。）２３４ｍｇを得た。
　本発明化合物６３
Figure JPOXMLDOC01-appb-C000073
 1H-NMR (CDCl3) δ: 1.07 (3H, t, J = 7.4 Hz), 1.85-1.88 (2H, m), 4.04 (2H, t, J = 6.5 Hz), 6.79 (1H, t, J = 8.2 Hz), 7.11 (1H, td, J = 8.3, 1.6 Hz), 7.52 (1H, dd, J = 8.3, 4.2 Hz), 8.07 (1H, t, J = 7.5 Hz), 8.19-8.29 (4H, m), 8.42 (1H, d, J = 1.4 Hz), 9.03 (1H, dd, J = 4.0, 1.3 Hz). Production Example 63
323 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 155 mg of bromopropane and 447 mg of cesium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 4 hours and 30 minutes. A 1 mol / L-aqueous sodium hydroxide solution was added to the reaction mixture, and the mixture was cooled with ice. The precipitated solid was filtered and washed with hexane. The obtained solid was dried under reduced pressure to obtain 234 mg of 2′-fluoro-3′-propoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 63).
Compound 63 of the present invention
Figure JPOXMLDOC01-appb-C000073
 1 H-NMR (CDCl 3 ) δ: 1.07 (3H, t, J = 7.4 Hz), 1.85-1.88 (2H, m), 4.04 (2H, t, J = 6.5 Hz), 6.79 (1H, t, J = 8.2 Hz), 7.11 (1H, td, J = 8.3, 1.6 Hz), 7.52 (1H, dd, J = 8.3, 4.2 Hz), 8.07 (1H, t, J = 7.5 Hz), 8.19-8.29 (4H , m), 8.42 (1H, d, J = 1.4 Hz), 9.03 (1H, dd, J = 4.0, 1.3 Hz).
製造例６４
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２７０ｍｇ、３－エトキシプロピルメタンスルホネート１９２ｍｇ及び炭酸セシウム３７４ｍｇをＤＭＦ４ｍｌに加え、室温で１９時間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えて、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄した後、無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をへキサンで洗浄することで２'－フルオロ－３'－（３－エトキシプロピルオキシ）キノリン－６－カルボン酸アニリド（以下、本発明化合物６４と記す。）２８７ｍｇを得た。
　本発明化合物６４
Figure JPOXMLDOC01-appb-C000074
 1H-NMR (CDCl3) δ: 1.22 (3H, t, J = 7.0 Hz), 2.08-2.14 (2H, m), 3.52 (2H, q, J = 7.0 Hz), 3.63 (2H, t, J = 6.0 Hz), 4.19 (2H, t, J = 6.2 Hz), 6.82 (1H, t, J = 8.3 Hz), 7.10-7.14 (1H, m), 7.52 (1H, dd, J = 8.3, 4.2 Hz), 8.08 (1H, t, J = 7.4 Hz), 8.19-8.30 (4H, m), 8.42 (1H, d, J = 1.7 Hz), 9.04 (1H, d, J = 3.1 Hz). Production Example 64
270 mg of 2'-fluoro-3'-hydroxy-quinoline-6-carboxylic acid anilide, 192 mg of 3-ethoxypropylmethanesulfonate and 374 mg of cesium carbonate were added to 4 ml of DMF, and the mixture was stirred at room temperature for 19 hours. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was washed with hexane to obtain 287 mg of 2′-fluoro-3 ′-(3-ethoxypropyloxy) quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 64).
Compound 64 of the present invention
Figure JPOXMLDOC01-appb-C000074
 1 H-NMR (CDCl 3 ) δ: 1.22 (3H, t, J = 7.0 Hz), 2.08-2.14 (2H, m), 3.52 (2H, q, J = 7.0 Hz), 3.63 (2H, t, J = 6.0 Hz), 4.19 (2H, t, J = 6.2 Hz), 6.82 (1H, t, J = 8.3 Hz), 7.10-7.14 (1H, m), 7.52 (1H, dd, J = 8.3, 4.2 Hz ), 8.08 (1H, t, J = 7.4 Hz), 8.19-8.30 (4H, m), 8.42 (1H, d, J = 1.7 Hz), 9.04 (1H, d, J = 3.1 Hz).
製造例６５
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２９５ｍｇ、３－ブロモ－１－プロペン１２７ｍｇ及び炭酸セシウム４０９ｍｇをＤＭＦ５ｍｌに加え、室温で３０分間攪拌した。反応混合物に水を加えてから氷冷した後、析出した固体をろ過し、へキサンで洗浄した。得られた固体を減圧下乾燥し、２'－フルオロ－３'－（２－プロペニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物６５と記す。）３０１ｍｇを得た。
　本発明化合物６５
Figure JPOXMLDOC01-appb-C000075
 1H-NMR (CDCl3) δ: 4.65 (2H, d, J = 5.3 Hz), 5.33 (1H, d, J = 10.6 Hz), 5.45 (1H, d, J = 17.1 Hz), 6.03-6.12 (1H, m), 6.80 (1H, t, J = 8.1 Hz), 7.11 (1H, td, J = 8.4, 1.8 Hz), 7.52 (1H, dd, J = 8.2, 4.3 Hz), 8.08-8.32 (5H, m), 8.42 (1H, s), 9.03 (1H, dd, J = 3.9, 1.4 Hz). Production Example 65
295 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 127 mg of 3-bromo-1-propene and 409 mg of cesium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 30 minutes. After adding water to the reaction mixture and cooling with ice, the precipitated solid was filtered and washed with hexane. The obtained solid was dried under reduced pressure to obtain 301 mg of 2′-fluoro-3 ′-(2-propenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 65).
Compound 65 of the present invention
Figure JPOXMLDOC01-appb-C000075
 1 H-NMR (CDCl 3 ) δ: 4.65 (2H, d, J = 5.3 Hz), 5.33 (1H, d, J = 10.6 Hz), 5.45 (1H, d, J = 17.1 Hz), 6.03-6.12 ( 1H, m), 6.80 (1H, t, J = 8.1 Hz), 7.11 (1H, td, J = 8.4, 1.8 Hz), 7.52 (1H, dd, J = 8.2, 4.3 Hz), 8.08-8.32 (5H , m), 8.42 (1H, s), 9.03 (1H, dd, J = 3.9, 1.4 Hz).
製造例６６
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド３１７ｍｇ、ブロモオクタン２２１ｍｇ及び炭酸セシウム４０２ｍｇをＤＭＦ５ｍｌに加え、室温で１１時間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えて、酢酸エチルで抽出した後、飽和食塩水で洗浄した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－オクチルオキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物６６と記す。）３４８ｍｇを得た。
　本発明化合物６６
Figure JPOXMLDOC01-appb-C000076
 1H-NMR (CDCl3) δ: 0.90 (3H, t, J = 6.7 Hz), 1.31-1.43 (10H, m), 1.80-1.87 (2H, m), 4.07 (2H, t, J = 6.6 Hz), 6.79 (1H, dd, J = 8.2, 7.0 Hz), 7.11 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.4 Hz), 8.07 (1H, t, J = 6.8 Hz), 8.24 (4H, tt, J = 27.4, 9.1 Hz), 8.42 (1H, d, J = 2.0 Hz), 9.03 (1H, dd, J = 4.1, 1.7 Hz). Production Example 66
317 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 221 mg of bromooctane and 402 mg of cesium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 11 hours. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 348 mg of 2′-fluoro-3′-octyloxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 66).
Compound 66 of the present invention
Figure JPOXMLDOC01-appb-C000076
 1 H-NMR (CDCl 3 ) δ: 0.90 (3H, t, J = 6.7 Hz), 1.31-1.43 (10H, m), 1.80-1.87 (2H, m), 4.07 (2H, t, J = 6.6 Hz ), 6.79 (1H, dd, J = 8.2, 7.0 Hz), 7.11 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.4 Hz), 8.07 (1H, t, J = 6.8 Hz), 8.24 (4H, tt, J = 27.4, 9.1 Hz), 8.42 (1H, d, J = 2.0 Hz), 9.03 (1H, dd, J = 4.1, 1.7 Hz).
製造例６７
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド３２０ｍｇ、ヨウ化エチル１９４ｍｇ及び炭酸セシウム４４３ｍｇをＤＭＦ５ｍｌに加え、室温で４時間３０分間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えて、酢酸エチルで抽出した後、飽和食塩水で洗浄した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－エトキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物６７と記す。）２８５ｍｇを得た。
　本発明化合物６７
Figure JPOXMLDOC01-appb-C000077
 1H-NMR (CDCl3) δ: 1.47 (3H, t, J = 7.1 Hz), 4.15 (2H, q, J = 7.0 Hz), 6.79 (1H, td, J = 8.2, 1.2 Hz), 7.11 (1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.4 Hz), 8.07 (1H, t, J = 6.8 Hz), 8.19-8.29 (4H, m), 8.42 (1H, d, J = 2.0 Hz), 9.03 (1H, dd, J = 4.1, 1.7 Hz). Production Example 67
320 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 194 mg of ethyl iodide and 443 mg of cesium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 4 hours and 30 minutes. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate and washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 285 mg of 2′-fluoro-3′-ethoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 67).
Compound 67 of the present invention
Figure JPOXMLDOC01-appb-C000077
 1 H-NMR (CDCl 3 ) δ: 1.47 (3H, t, J = 7.1 Hz), 4.15 (2H, q, J = 7.0 Hz), 6.79 (1H, td, J = 8.2, 1.2 Hz), 7.11 ( 1H, td, J = 8.4, 2.0 Hz), 7.52 (1H, dd, J = 8.3, 4.4 Hz), 8.07 (1H, t, J = 6.8 Hz), 8.19-8.29 (4H, m), 8.42 (1H , d, J = 2.0 Hz), 9.03 (1H, dd, J = 4.1, 1.7 Hz).
製造例６８
　２－フルオロ－３－フェノキシアニリン０．２０ｇ及びトリエチルアミン０．１３ｇをＴＨＦ４ｍｌに加え、氷冷下でキノリン－６－カルボン酸塩化物の塩酸塩０．２３ｇを加え、室温で１時間攪拌した。反応混合物を濾過し、濾液を減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－フェノキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物６８と記す。）０．１７ｇを得た。
　本発明化合物６８
Figure JPOXMLDOC01-appb-C000078
 1H-NMR (CDCl3) δ: 6.86 (1H, td, J = 8.1, 1.5 Hz), 7.02-7.05 (2H, m), 7.11-7.20 (2H, m), 7.34-7.39 (2H, m), 7.52 (1H, dd, J = 8.3, 4.4 Hz), 8.18 (1H, dd, J = 8.8, 2.0 Hz), 8.23-8.33 (4H, m), 8.42 (1H, d, J = 2.0 Hz), 9.04 (1H, dd, J = 4.4, 1.7 Hz). Production Example 68
0.20 g of 2-fluoro-3-phenoxyaniline and 0.13 g of triethylamine were added to 4 ml of THF, 0.23 g of hydrochloride of quinoline-6-carboxylic acid chloride was added under ice cooling, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 0.17 g of 2′-fluoro-3′-phenoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 68).
Compound 68 of the present invention
Figure JPOXMLDOC01-appb-C000078
 1 H-NMR (CDCl 3 ) δ: 6.86 (1H, td, J = 8.1, 1.5 Hz), 7.02-7.05 (2H, m), 7.11-7.20 (2H, m), 7.34-7.39 (2H, m) , 7.52 (1H, dd, J = 8.3, 4.4 Hz), 8.18 (1H, dd, J = 8.8, 2.0 Hz), 8.23-8.33 (4H, m), 8.42 (1H, d, J = 2.0 Hz), 9.04 (1H, dd, J = 4.4, 1.7 Hz).
製造例６９
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド３１６ｍｇ、２－ヨードプロパン２０９ｍｇ及び炭酸セシウム４３８ｍｇをＤＭＦ５ｍｌに加え、室温で２０時間３０分間攪拌した。反応混合物に水を加えて、酢酸エチルで抽出した。有機層を１モル／Ｌ－水酸化ナトリウム水溶液及び飽和食塩水で順次洗浄し、無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－（１－メチルエトキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物６９と記す。）２７３ｍｇを得た。
　本発明化合物６９
Figure JPOXMLDOC01-appb-C000079
 1H-NMR (CDCl3) δ: 1.35 (6H, t, J = 12.2 Hz), 4.51-4.58 (1H, m), 6.79 (1H, td, J = 8.2, 1.2 Hz), 7.06 (1H, td, J = 8.3, 1.9 Hz), 7.46 (1H, dd, J = 8.2, 4.1 Hz), 7.97-8.01 (1H, m), 8.12-8.24 (3H, m), 8.38 (2H, ｍ, J = 6.8, 1.9 Hz), 8.98 (1H, dd, J = 4.2, 1.6 Hz). Production Example 69
316 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 209 mg of 2-iodopropane and 438 mg of cesium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 20 hours and 30 minutes. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with 1 mol / L-aqueous sodium hydroxide solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 273 mg of 2′-fluoro-3 ′-(1-methylethoxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 69). .
Compound 69 of the present invention
Figure JPOXMLDOC01-appb-C000079
 1 H-NMR (CDCl 3 ) δ: 1.35 (6H, t, J = 12.2 Hz), 4.51-4.58 (1H, m), 6.79 (1H, td, J = 8.2, 1.2 Hz), 7.06 (1H, td , J = 8.3, 1.9 Hz), 7.46 (1H, dd, J = 8.2, 4.1 Hz), 7.97-8.01 (1H, m), 8.12-8.24 (3H, m), 8.38 (2H, m, J = 6.8 , 1.9 Hz), 8.98 (1H, dd, J = 4.2, 1.6 Hz).
製造例７０
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２９６ｍｇ、１－ブロモブタン１５７ｍｇ及び炭酸カリウム１７４ｍｇをＤＭＦ５ｍｌに加え、室温で１５時間３０分間攪拌した。反応混合物に水を加えて、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－ブトキシ－キノリン－６－カルボン酸アニリド（以下、本発明化合物７０と記す。）３１０ｍｇを得た。
　本発明化合物７０
Figure JPOXMLDOC01-appb-C000080
 1H-NMR (CDCl3) δ: 0.99 (3H, t, J = 7.4 Hz), 1.49-1.57 (2H, m), 1.79-1.84 (2H, m), 4.07 (2H, t, J = 6.5 Hz), 6.79 (1H, t, J = 8.2 Hz), 7.10 (1H, td, J = 8.5, 1.7 Hz), 7.51 (1H, dd, J = 8.3, 4.2 Hz), 8.03-8.41 (6H, m), 9.02 (1H, dd, J = 3.9, 1.4 Hz). Production Example 70
296 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 157 mg of 1-bromobutane and 174 mg of potassium carbonate were added to 5 ml of DMF and stirred at room temperature for 15 hours and 30 minutes. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 310 mg of 2′-fluoro-3′-butoxy-quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 70).
Compound 70 of the present invention
Figure JPOXMLDOC01-appb-C000080
 1 H-NMR (CDCl 3 ) δ: 0.99 (3H, t, J = 7.4 Hz), 1.49-1.57 (2H, m), 1.79-1.84 (2H, m), 4.07 (2H, t, J = 6.5 Hz ), 6.79 (1H, t, J = 8.2 Hz), 7.10 (1H, td, J = 8.5, 1.7 Hz), 7.51 (1H, dd, J = 8.3, 4.2 Hz), 8.03-8.41 (6H, m) , 9.02 (1H, dd, J = 3.9, 1.4 Hz).
製造例７１
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２８８ｍｇ、４－ブロモ－１－ブテン１５１ｍｇ及び炭酸セシウム３９９ｍｇをＤＭＦ１０ｍｌに加え、室温で１２時間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えて、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－（３－ブテニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物７１と記す。）１２８ｍｇを得た。
　本発明化合物７１
Figure JPOXMLDOC01-appb-C000081
 1H-NMR (CDCl3) δ: 2.60 (2H, q, J = 6.5 Hz), 4.13 (2H, t, J = 6.7 Hz), 5.17 (2H, dd, J = 23.8, 13.8 Hz), 5.90-5.94 (1H, m), 6.80 (1H, t, J = 7.9 Hz), 7.11 (1H, t, J = 7.8 Hz), 7.52 (1H, dd, J = 8.3, 4.1 Hz), 8.14-8.24 (5H, m), 8.41 (1H, s), 9.03 (1H, d, J = 3.7 Hz). Production Example 71
288 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 151 mg of 4-bromo-1-butene and 399 mg of cesium carbonate were added to 10 ml of DMF, and the mixture was stirred at room temperature for 12 hours. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 128 mg of 2′-fluoro-3 ′-(3-butenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 71).
Compound 71 of the present invention
Figure JPOXMLDOC01-appb-C000081
 1 H-NMR (CDCl 3 ) δ: 2.60 (2H, q, J = 6.5 Hz), 4.13 (2H, t, J = 6.7 Hz), 5.17 (2H, dd, J = 23.8, 13.8 Hz), 5.90- 5.94 (1H, m), 6.80 (1H, t, J = 7.9 Hz), 7.11 (1H, t, J = 7.8 Hz), 7.52 (1H, dd, J = 8.3, 4.1 Hz), 8.14-8.24 (5H , m), 8.41 (1H, s), 9.03 (1H, d, J = 3.7 Hz).
製造例７２
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド３００ｍｇ、３－ブロモ－１－プロピン１３９ｍｇ及び炭酸カリウム１７６ｍｇをＤＭＦ５ｍｌに加え、室温で１時間攪拌した。反応混合物に水を加えて氷冷後、析出した固体をろ過し、１モル／Ｌ－水酸化ナトリウム水溶液及びへキサンで順次洗浄した。得られた固体を減圧下乾燥し、２'－フルオロ－３'－（２－プロピニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物７２と記す。）３４０ｍｇを得た。
　本発明化合物７２
Figure JPOXMLDOC01-appb-C000082
 1H-NMR (CDCl3) δ: 2.57 (1H, t, J = 2.2 Hz), 4.81 (2H, s), 6.94 (1H, t, J = 7.8 Hz), 7.15 (1H, t, J = 8.1 Hz), 7.52 (1H, d, J = 4.3 Hz), 8.16-8.42 (6H, m), 9.02-9.05 (1H, m). Production Example 72
300 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 139 mg of 3-bromo-1-propyne and 176 mg of potassium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture and the mixture was ice-cooled. The precipitated solid was filtered and washed successively with 1 mol / L-aqueous sodium hydroxide solution and hexane. The obtained solid was dried under reduced pressure to obtain 340 mg of 2′-fluoro-3 ′-(2-propynyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 72).
Compound 72 of the present invention
Figure JPOXMLDOC01-appb-C000082
 1 H-NMR (CDCl 3 ) δ: 2.57 (1H, t, J = 2.2 Hz), 4.81 (2H, s), 6.94 (1H, t, J = 7.8 Hz), 7.15 (1H, t, J = 8.1 Hz), 7.52 (1H, d, J = 4.3 Hz), 8.16-8.42 (6H, m), 9.02-9.05 (1H, m).
製造例７３
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド３１９ｍｇ、７－ブロモ－１－ヘプテン１８２ｍｇ及び炭酸セシウム４４２ｍｇをＤＭＦ５ｍｌに加え、室温で６時間３０分間攪拌した。反応混合物に水を加えて、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－（６－へプテニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物７３と記す。）３８８ｍｇを得た。
　本発明化合物７３
Figure JPOXMLDOC01-appb-C000083
 1H-NMR (CDCl3) δ: 1.49-1.51 (4H, m), 1.81-1.88 (2H, m), 2.10-2.12 (2H, m), 4.07 (2H, t, J = 6.5 Hz), 4.90-5.06 (2H, m), 5.76-5.88 (1H, m), 6.73-6.82 (1H, m), 7.06-7.16 (1H, m), 7.47-7.56 (1H, m), 8.02-8.11 (1H, m), 8.20-8.27 (4H, m), 8.41 (1H, d, J = 1.9 Hz), 9.03 (1H, dd, J = 4.2, 1.6 Hz). Production Example 73
319 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 182 mg of 7-bromo-1-heptene and 442 mg of cesium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 6 hours and 30 minutes. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 388 mg of 2′-fluoro-3 ′-(6-heptenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 73). .
Compound 73 of the present invention
Figure JPOXMLDOC01-appb-C000083
 1 H-NMR (CDCl 3 ) δ: 1.49-1.51 (4H, m), 1.81-1.88 (2H, m), 2.10-2.12 (2H, m), 4.07 (2H, t, J = 6.5 Hz), 4.90 -5.06 (2H, m), 5.76-5.88 (1H, m), 6.73-6.82 (1H, m), 7.06-7.16 (1H, m), 7.47-7.56 (1H, m), 8.02-8.11 (1H, m), 8.20-8.27 (4H, m), 8.41 (1H, d, J = 1.9 Hz), 9.03 (1H, dd, J = 4.2, 1.6 Hz).
製造例７４
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド３０５ｍｇ、４－メトキシブチルメタンスルホネート２１７ｍｇ及び炭酸セシウム４２３ｍｇをＤＭＦ５ｍｌに加え、室温で１９時間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えて、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－（４－メトキシブトキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物７４と記す。）３５０ｍｇを得た。
　本発明化合物７４
Figure JPOXMLDOC01-appb-C000084
 1H -NMR (CDCl3) δ: 1.77-1.79 (2H, m), 1.91 (2H, t, J = 7.3 Hz), 3.36 (3H, s), 3.46 (2H, t, J = 6.3 Hz), 4.09 (2H, t, J = 6.3 Hz), 6.79 (1H, td, J = 8.2, 1.4 Hz), 7.10 (1H, s), 7.51 (1H, dd, J = 8.3, 4.4 Hz), 8.05 (1H, s), 8.16-8.31 (4H, m), 8.41 (1H, d, J = 2.0 Hz), 9.02 (1H, dd, J = 4.4, 1.7 Hz). Production Example 74
2'-Fluoro-3'-hydroxy-quinoline-6-carboxylic acid anilide (305 mg), 4-methoxybutylmethanesulfonate (217 mg) and cesium carbonate (423 mg) were added to DMF (5 ml), and the mixture was stirred at room temperature for 19 hours. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 350 mg of 2′-fluoro-3 ′-(4-methoxybutoxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 74). .
Compound 74 of the present invention
Figure JPOXMLDOC01-appb-C000084
 1 H -NMR (CDCl 3 ) δ: 1.77-1.79 (2H, m), 1.91 (2H, t, J = 7.3 Hz), 3.36 (3H, s), 3.46 (2H, t, J = 6.3 Hz), 4.09 (2H, t, J = 6.3 Hz), 6.79 (1H, td, J = 8.2, 1.4 Hz), 7.10 (1H, s), 7.51 (1H, dd, J = 8.3, 4.4 Hz), 8.05 (1H , s), 8.16-8.31 (4H, m), 8.41 (1H, d, J = 2.0 Hz), 9.02 (1H, dd, J = 4.4, 1.7 Hz).
製造例７５
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２９４ｍｇ、１－ブロモ－２－ペンテン１７０ｍｇ及び炭酸セシウム４０７ｍｇをＤＭＦ５ｍｌに加え、室温で１時間３０分間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えて、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－（２－ペンテニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物７５と記す。）３１２ｍｇを得た。
　本発明化合物７５
Figure JPOXMLDOC01-appb-C000085
 1H-NMR (CDCl3) δ: 1.01 (3H, t, J = 11.0 Hz), 2.10-2.16 (2H, m), 4.54-4.69 (2H, m), 5.22-5.95 (2H, m), 6.80 (1H, td, J = 8.2, 1.2 Hz), 7.04-7.12 (1H, m), 7.50 (1H, dd, J = 8.3, 4.2 Hz), 8.03-8.41 (6H, m), 9.02 (1H, dd, J = 4.1, 1.7 Hz). Production Example 75
294 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 170 mg of 1-bromo-2-pentene and 407 mg of cesium carbonate were added to 5 ml of DMF, and the mixture was stirred at room temperature for 1 hour and 30 minutes. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 312 mg of 2′-fluoro-3 ′-(2-pentenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 75). .
Compound 75 of the present invention
Figure JPOXMLDOC01-appb-C000085
 1 H-NMR (CDCl 3 ) δ: 1.01 (3H, t, J = 11.0 Hz), 2.10-2.16 (2H, m), 4.54-4.69 (2H, m), 5.22-5.95 (2H, m), 6.80 (1H, td, J = 8.2, 1.2 Hz), 7.04-7.12 (1H, m), 7.50 (1H, dd, J = 8.3, 4.2 Hz), 8.03-8.41 (6H, m), 9.02 (1H, dd , J = 4.1, 1.7 Hz).
製造例７６
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド３０２ｍｇ、１－ブロモ－３－メチルブタン１７８ｍｇ及び炭酸セシウム４１８ｍｇをＤＭＦ５ｍｌに加え、室温で１０時間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えて、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－（３－メチルブトキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物７６と記す。）３４３ｍｇを得た。
　本発明化合物７６
Figure JPOXMLDOC01-appb-C000086
 1H-NMR (CDCl3) δ: 0.98 (6H, d, J = 6.6 Hz), 1.70-1.98 (3H, m), 4.09 (2H, t, J = 6.6 Hz), 6.79 (1H, td, J = 8.2, 1.3 Hz), 7.09 (1H, td, J = 8.4, 1.9 Hz), 7.50 (1H, dd, J = 8.3, 4.4 Hz), 8.03 (1H, dd, J = 13.2, 5.6 Hz), 8.17-8.26 (4H, m), 8.40 (1H, d, J = 1.7 Hz), 9.01 (1H, dd, J = 4.1, 1.7 Hz). Production Example 76
302 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 178 mg of 1-bromo-3-methylbutane and 418 mg of cesium carbonate were added to 5 ml of DMF and stirred at room temperature for 10 hours. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 343 mg of 2′-fluoro-3 ′-(3-methylbutoxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 76). .
Compound 76 of the present invention
Figure JPOXMLDOC01-appb-C000086
 1 H-NMR (CDCl 3 ) δ: 0.98 (6H, d, J = 6.6 Hz), 1.70-1.98 (3H, m), 4.09 (2H, t, J = 6.6 Hz), 6.79 (1H, td, J = 8.2, 1.3 Hz), 7.09 (1H, td, J = 8.4, 1.9 Hz), 7.50 (1H, dd, J = 8.3, 4.4 Hz), 8.03 (1H, dd, J = 13.2, 5.6 Hz), 8.17 -8.26 (4H, m), 8.40 (1H, d, J = 1.7 Hz), 9.01 (1H, dd, J = 4.1, 1.7 Hz).
製造例７７
　２'－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２９７ｍｇ、１－ブロモ－２－ブテン１５７ｍｇ及び炭酸カリウム１７５ｍｇをＤＭＦ５ｍｌに加え、室温で１時間攪拌した。反応混合物に１モル／Ｌ－水酸化ナトリウム水溶液を加えて、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２'－フルオロ－３'－（２－ブテニルオキシ）－キノリン－６－カルボン酸アニリド（以下、本発明化合物７７と記す。）３２０ｍｇを得た。
　本発明化合物７７
Figure JPOXMLDOC01-appb-C000087
 1H-NMR (CDCl3) δ: 1.77-1.78 (3H, m), 4.57-4.71 (2H, m), 5.73-5.92 (2H, m), 6.80 (1H, t, J = 7.6 Hz), 7.11 (1H, td, J = 8.3, 1.9 Hz), 7.52 (1H, dd, J = 8.3, 4.2 Hz), 8.07-8.42 (6H, m), 9.03 (1H, dd, J = 4.2, 1.6 Hz). Production Example 77
297 mg of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide, 157 mg of 1-bromo-2-butene and 175 mg of potassium carbonate were added to 5 ml of DMF and stirred at room temperature for 1 hour. To the reaction mixture was added 1 mol / L-aqueous sodium hydroxide solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, so as to obtain 320 mg of 2′-fluoro-3 ′-(2-butenyloxy) -quinoline-6-carboxylic acid anilide (hereinafter referred to as the present compound 77).
Compound 77 of the present invention
Figure JPOXMLDOC01-appb-C000087
 1 H-NMR (CDCl 3 ) δ: 1.77-1.78 (3H, m), 4.57-4.71 (2H, m), 5.73-5.92 (2H, m), 6.80 (1H, t, J = 7.6 Hz), 7.11 (1H, td, J = 8.3, 1.9 Hz), 7.52 (1H, dd, J = 8.3, 4.2 Hz), 8.07-8.42 (6H, m), 9.03 (1H, dd, J = 4.2, 1.6 Hz).
　次に、本発明化合物の製造中間体の製造について参考製造例を示す。 Next, reference production examples are shown for the production of the production intermediate of the compound of the present invention.
参考製造例１
　水酸化ナトリウム０．９５ｇを水１７ｍｌに溶解し、ここに－１０℃で臭素０．３３ｍｌ及び２－フルオロ－３－メトキシベンズアミド１．０ｇを順次混合した。この混合物を０℃以下で３０分間、次いで７０℃で１時間撹拌した。室温付近まで放冷した反応混合物に水を加え、クロロホルムで抽出した。有機層を硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２－フルオロ－３－メトキシアニリン０．２９ｇを得た。
　２－フルオロ－３－メトキシアニリン
Figure JPOXMLDOC01-appb-C000088
 1H-NMR (CDCl3) δ: 3.72 (2H, s), 3.86 (3H, s), 6.35-6.42 (2H, m), 6.84 (1H, td, J = 8.2, 2.0 Hz). Reference production example 1
0.95 g of sodium hydroxide was dissolved in 17 ml of water, and 0.33 ml of bromine and 1.0 g of 2-fluoro-3-methoxybenzamide were sequentially mixed at −10 ° C. The mixture was stirred at 0 ° C. or lower for 30 minutes and then at 70 ° C. for 1 hour. Water was added to the reaction mixture allowed to cool to around room temperature, and the mixture was extracted with chloroform. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain 0.29 g of 2-fluoro-3-methoxyaniline.
2-Fluoro-3-methoxyaniline
Figure JPOXMLDOC01-appb-C000088
 1 H-NMR (CDCl 3 ) δ: 3.72 (2H, s), 3.86 (3H, s), 6.35-6.42 (2H, m), 6.84 (1H, td, J = 8.2, 2.0 Hz).
参考製造例２
　キノリン－６－カルボン酸塩化物の塩酸塩１．０ｇ及び３－ヒドロキシアニリン２．０ｇをＴＨＦ２０ｍｌに加え、４時間加熱還流した。室温付近まで放冷した反応混合物を減圧下濃縮し、得られた残渣に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出した。有機層を水及び飽和食塩水で順次洗浄し、硫酸マグネシウムで乾燥後、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して３'－ヒドロキシ－キノリン－６－カルボン酸アニリド０．６０ｇを得た。
　３'－ヒドロキシ－キノリン－６－カルボン酸アニリド
Figure JPOXMLDOC01-appb-C000089
 1H-NMR (DMSO-D6) δ: 6.52-6.55 (1H, m), 7.12-7.23 (2H, m), 7.40-7.42 (1H, m), 7.65 (1H, dd, J = 8.3, 4.2 Hz), 8.13 (1H, d, J = 8.8 Hz), 8.24 (1H, dd, J = 8.8, 1.9 Hz), 8.54 (1H, d, J = 7.7 Hz), 8.61 (1H, d, J = 1.9 Hz), 9.02 (1H, dd, J = 4.2, 1.7 Hz), 9.46 (1H, s), 10.38 (1H, s). Reference production example 2
1.0 g of hydrochloride of quinoline-6-carboxylic acid chloride and 2.0 g of 3-hydroxyaniline were added to 20 ml of THF, and the mixture was heated to reflux for 4 hours. The reaction mixture was allowed to cool to near room temperature and concentrated under reduced pressure. A saturated aqueous sodium hydrogen carbonate solution was added to the resulting residue, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.60 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide.
3'-hydroxy-quinoline-6-carboxylic acid anilide
Figure JPOXMLDOC01-appb-C000089
 1 H-NMR (DMSO-D 6 ) δ: 6.52-6.55 (1H, m), 7.12-7.23 (2H, m), 7.40-7.42 (1H, m), 7.65 (1H, dd, J = 8.3, 4.2 Hz), 8.13 (1H, d, J = 8.8 Hz), 8.24 (1H, dd, J = 8.8, 1.9 Hz), 8.54 (1H, d, J = 7.7 Hz), 8.61 (1H, d, J = 1.9 Hz), 9.02 (1H, dd, J = 4.2, 1.7 Hz), 9.46 (1H, s), 10.38 (1H, s).
参考製造例３
　３－ニトロフェノール１５ｇ、クロロ（１，１－ジメチルエチル）ジメチルシラン１９ｇ、イミダゾール１１ｇ及びＤＭＦ２００ｍｌの混合物を室温で３時間撹拌した。反応混合物に水を加えヘキサンで２回抽出した。有機層を１％塩酸、飽和炭酸水素ナトリウム水溶液及び飽和食塩水で順次洗浄後、硫酸マグネシウムで乾燥し、減圧下濃縮して（１，１－ジメチルエチル）ジメチルシリル－（３－ニトロフェニル）エーテル３０ｇを得た。
　（１，１－ジメチルエチル）ジメチルシリル－（３－ニトロフェニル）エーテル
Figure JPOXMLDOC01-appb-C000090
 1H-NMR (CDCl3) δ: 0.25 (6H, s), 1.00 (9H, s), 7.14-7.18 (1H, m), 7.38 (1H, t, J = 8.2 Hz), 7.66 (1H, t, J = 2.2 Hz), 7.81-7.84 (1H, m). Reference production example 3
A mixture of 15 g of 3-nitrophenol, 19 g of chloro (1,1-dimethylethyl) dimethylsilane, 11 g of imidazole and 200 ml of DMF was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was extracted twice with hexane. The organic layer was washed successively with 1% hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to (1,1-dimethylethyl) dimethylsilyl- (3-nitrophenyl) ether. 30 g was obtained.
(1,1-Dimethylethyl) dimethylsilyl- (3-nitrophenyl) ether
Figure JPOXMLDOC01-appb-C000090
 1 H-NMR (CDCl 3 ) δ: 0.25 (6H, s), 1.00 (9H, s), 7.14-7.18 (1H, m), 7.38 (1H, t, J = 8.2 Hz), 7.66 (1H, t , J = 2.2 Hz), 7.81-7.84 (1H, m).
参考製造例４
　（１，１－ジメチルエチル）ジメチルシリル－（３－ニトロフェニル）エーテル３０ｇ、１０％パラジウム炭素０．９０ｇ及びエタノール１５０ｍｌの混合物を水素気流下で水素ガスの吸収がなくなるまで撹拌した。反応混合物をセライト（登録商標）を通して濾過し、濾液を減圧下で濃縮して３－［（１，１－ジメチルエチル）ジメチルシリルオキシ］アニリン２４ｇを得た。
　３－［（１，１－ジメチルエチル）ジメチルシリルオキシ］アニリン
Figure JPOXMLDOC01-appb-C000091
 1H-NMR (CDCl3)δ: 0.18 (6H, s), 0.97 (9H, s), 3.59 (2H, s), 6.19 (1H, t, J = 2.2 Hz), 6.24-6.31 (2H, m), 6.98 (1H, t, J = 8.0 Hz). Reference production example 4
A mixture of 30 g of (1,1-dimethylethyl) dimethylsilyl- (3-nitrophenyl) ether, 0.90 g of 10% palladium on carbon and 150 ml of ethanol was stirred under a hydrogen stream until there was no absorption of hydrogen gas. The reaction mixture was filtered through Celite (registered trademark), and the filtrate was concentrated under reduced pressure to obtain 24 g of 3-[(1,1-dimethylethyl) dimethylsilyloxy] aniline.
3-[(1,1-Dimethylethyl) dimethylsilyloxy] aniline
Figure JPOXMLDOC01-appb-C000091
 1 H-NMR (CDCl 3 ) δ: 0.18 (6H, s), 0.97 (9H, s), 3.59 (2H, s), 6.19 (1H, t, J = 2.2 Hz), 6.24-6.31 (2H, m ), 6.98 (1H, t, J = 8.0 Hz).
参考製造例５
　３－[（１，１－ジメチルエチル）ジメチルシリルオキシ]アニリン２０ｇ、キノリン－６－カルボン酸１６ｇ、ＢＯＰ試薬４８ｇ、トリエチルアミン２５ｍｌ及びＤＭＦ５００ｍｌの混合物を室温で１時間撹拌した。反応混合物に水を加え、酢酸エチルで３回抽出した。有機層を水及び飽和食塩水で順次洗浄後、硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣を酢酸エチルに混合してから濾過し、濾液を減圧下で濃縮して３'－［（１，１－ジメチルエチル）ジメチルシリルオキシ］－キノリン－６－カルボン酸アニリド３５ｇを得た。
　３'－[（１，１－ジメチルエチル）ジメチルシリルオキシ]－キノリン－６－カルボン酸アニリド
Figure JPOXMLDOC01-appb-C000092
 1H-NMR (CDCl3) δ: 0.24 (6H, s), 1.00 (9H, s), 6.67 (1H, dt, J = 7.2, 2.1 Hz), 7.21-7.23 (2H, m), 7.39 (1H, s), 7.49 (1H, dd, J = 8.3, 4.1 Hz), 8.10 (1H, s), 8.13 (1H, dd, J = 8.8, 2.0 Hz), 8.18 (1H, d, J = 8.8 Hz), 8.23-8.26 (1H, m), 8.38 (1H, d, J = 1.7 Hz), 9.00 (1H, dd, J = 4.1, 1.7 Hz). Reference production example 5
A mixture of 20 g of 3-[(1,1-dimethylethyl) dimethylsilyloxy] aniline, 16 g of quinoline-6-carboxylic acid, 48 g of BOP reagent, 25 ml of triethylamine and 500 ml of DMF was stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was mixed with ethyl acetate and filtered, and the filtrate was concentrated under reduced pressure to obtain 35 g of 3 ′-[(1,1-dimethylethyl) dimethylsilyloxy] -quinoline-6-carboxylic acid anilide. It was.
3 ′-[(1,1-dimethylethyl) dimethylsilyloxy] -quinoline-6-carboxylic acid anilide
Figure JPOXMLDOC01-appb-C000092
 1 H-NMR (CDCl 3 ) δ: 0.24 (6H, s), 1.00 (9H, s), 6.67 (1H, dt, J = 7.2, 2.1 Hz), 7.21-7.23 (2H, m), 7.39 (1H , s), 7.49 (1H, dd, J = 8.3, 4.1 Hz), 8.10 (1H, s), 8.13 (1H, dd, J = 8.8, 2.0 Hz), 8.18 (1H, d, J = 8.8 Hz) , 8.23-8.26 (1H, m), 8.38 (1H, d, J = 1.7 Hz), 9.00 (1H, dd, J = 4.1, 1.7 Hz).
参考製造例６
　３'－[（１，１－ジメチルエチル）ジメチルシリルオキシ]－キノリン－６－カルボン酸アニリド３５ｇ、水酸化リチウム１水和物１２ｇ及びＤＭＦ１５０ｍｌの混合物を室温で１０時間撹拌した。反応混合物に水を加え、ＭＴＢＥで抽出した。水層に５％塩酸を加えて該水層のｐＨを７以下に調整し、析出した固体を濾取した。得られた固体を水で洗浄後、減圧下で乾燥して３'－ヒドロキシ－キノリン－６－カルボン酸アニリド２８ｇを得た。
　３'－ヒドロキシ－キノリン－６－カルボン酸アニリド
Figure JPOXMLDOC01-appb-C000093
 Reference production example 6
A mixture of 35 g of 3 ′-[(1,1-dimethylethyl) dimethylsilyloxy] -quinoline-6-carboxylic acid anilide, 12 g of lithium hydroxide monohydrate and 150 ml of DMF was stirred at room temperature for 10 hours. Water was added to the reaction mixture and extracted with MTBE. 5% hydrochloric acid was added to the aqueous layer to adjust the pH of the aqueous layer to 7 or less, and the precipitated solid was collected by filtration. The obtained solid was washed with water and then dried under reduced pressure to obtain 28 g of 3′-hydroxy-quinoline-6-carboxylic acid anilide.
3'-hydroxy-quinoline-6-carboxylic acid anilide
Figure JPOXMLDOC01-appb-C000093
参考製造例７
　２－フルオロ－３－メトキシアニリン１０．０ｇに１０℃付近で、４８％臭化水素酸６．６gを混合し、該混合物を１００℃で２０時間加熱した。室温付近まで放冷した反応混合物を濾過し、得られた結晶に４８％臭化水素酸を１０ｍｌ加え、１００℃で２０時間加熱した。室温付近まで放冷した反応混合物に飽和炭酸水素ナトリウム水溶液を加え、酢酸エチルで抽出した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２－フルオロ－３－ヒドロキシアニリン４．８ｇを得た。
　２－フルオロ－３－ヒドロキシアニリン
Figure JPOXMLDOC01-appb-C000094
 1H-NMR (CDCl3) δ: 3.72 (2H, br s), 5.06 (1H, d, J = 3.7 Hz), 6.33 (1H, td, J = 8.0, 1.5 Hz), 6.39 (1H, td, J = 8.0, 1.5 Hz), 6.79 (1H, td, J = 8.1, 1.8 Hz). Reference production example 7
To 10.0 g of 2-fluoro-3-methoxyaniline was mixed 6.6 g of 48% hydrobromic acid at around 10 ° C., and the mixture was heated at 100 ° C. for 20 hours. The reaction mixture was allowed to cool to near room temperature, filtered, 10 ml of 48% hydrobromic acid was added to the obtained crystals, and the mixture was heated at 100 ° C. for 20 hours. A saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture allowed to cool to about room temperature, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain 4.8 g of 2-fluoro-3-hydroxyaniline.
2-Fluoro-3-hydroxyaniline
Figure JPOXMLDOC01-appb-C000094
 1 H-NMR (CDCl 3 ) δ: 3.72 (2H, br s), 5.06 (1H, d, J = 3.7 Hz), 6.33 (1H, td, J = 8.0, 1.5 Hz), 6.39 (1H, td, J = 8.0, 1.5 Hz), 6.79 (1H, td, J = 8.1, 1.8 Hz).
参考製造例８
　キノリン－６－カルボン酸塩化物の塩酸塩５．０２ｇ及びＴＨＦ５０ｍｌの混合物に、２－フルオロ－３－ヒドロキシアニリン１．２７ｇ、トリエチルアミン４．５ｇ及びＴＨＦ１０ｍｌの混合液を氷冷下にて加え、室温で１日間攪拌した。反応混合液を濾過し、濾液を減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付し、得られた生成物に２５％水酸化ナトリウム水溶液３ｍｌ及びメタノール１５ｍｌを加え、４０℃で３０分間攪拌した。室温付近まで放冷した反応混合物に飽和塩化アンモニウム水溶液を加えてｐＨを６から７の範囲内に調整した後、減圧下濃縮した。得られた残渣を酢酸エチルで抽出した。有機層を無水硫酸ナトリウムで乾燥し、減圧下濃縮して２’－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド４．６０ｇを得た。
　２’－フルオロ－３'－ヒドロキシ－キノリン－６－カルボン酸アニリド
Figure JPOXMLDOC01-appb-C000095
 1H-NMR (DMSO-D6) δ: 6.85 (1H, td, J = 7.9, 1.8 Hz), 6.97-7.07 (2H, m), 7.65 (1H, dd, J = 8.3, 4.1 Hz), 8.14 (1H, d, J = 8.8 Hz), 8.27 (1H, dd, J = 8.8, 2.0 Hz), 8.54 (1H, d, J = 7.3 Hz), 8.66 (1H, d, J = 1.7 Hz), 9.02 (1H, dd, J = 4.3, 1.6 Hz), 9.93 (1H, br s), 10.29 (1H, s). Reference production example 8
To a mixture of 5.02 g of quinoline-6-carboxylic acid chloride hydrochloride and 50 ml of THF, a mixture of 1.27 g of 2-fluoro-3-hydroxyaniline, 4.5 g of triethylamine and 10 ml of THF was added under ice-cooling. For 1 day. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography, 3 ml of 25% aqueous sodium hydroxide solution and 15 ml of methanol were added to the obtained product, and the mixture was stirred at 40 ° C. for 30 minutes. A saturated aqueous ammonium chloride solution was added to the reaction mixture which was allowed to cool to near room temperature to adjust the pH within the range of 6 to 7, and then concentrated under reduced pressure. The resulting residue was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 4.60 g of 2′-fluoro-3′-hydroxy-quinoline-6-carboxylic acid anilide.
2'-Fluoro-3'-hydroxy-quinoline-6-carboxylic acid anilide
Figure JPOXMLDOC01-appb-C000095
 1 H-NMR (DMSO-D 6 ) δ: 6.85 (1H, td, J = 7.9, 1.8 Hz), 6.97-7.07 (2H, m), 7.65 (1H, dd, J = 8.3, 4.1 Hz), 8.14 (1H, d, J = 8.8 Hz), 8.27 (1H, dd, J = 8.8, 2.0 Hz), 8.54 (1H, d, J = 7.3 Hz), 8.66 (1H, d, J = 1.7 Hz), 9.02 (1H, dd, J = 4.3, 1.6 Hz), 9.93 (1H, br s), 10.29 (1H, s).
参考製造例９
　２－フルオロフェノール２２ｇ、臭化銅（Ｉ）２．８ｇ、カリウム（１，１－ジメチルエトキシド）２３ｇ及びブロモベンゼン１２５ｇの混合物を、１５０℃で加熱攪拌し、ディーンスターク分離器を連結した反応容器内で１５０℃で加熱撹拌し、該ディーンスターク分離器により反応容器内から１，１－ジメチルエタノールを除去した。その後、反応混合物を２時間加熱還流した。室温付近まで放冷した反応混合物を減圧下濃縮し、残渣に酢酸エチルを加え、セライト（登録商標）を通してろ過した。ろ液を減圧下濃縮し、残渣をシリカゲルカラムクロマトグラフィーに付した。得られた２－フルオロ－ジフェニルエーテルを常圧下で蒸留して、２－フルオロ－ジフェニルエーテル２２ｇを得た。
　２－フルオロ－ジフェニルエーテル
Figure JPOXMLDOC01-appb-C000096
 1H-NMR (CDCl3) δ: 6.96-7.00 (2H, m), 7.03-7.21 (5H, m), 7.29-7.35 (2H, m). Reference production example 9
A reaction in which a mixture of 22 g of 2-fluorophenol, 2.8 g of copper (I) bromide, 23 g of potassium (1,1-dimethylethoxide) and 125 g of bromobenzene was heated and stirred at 150 ° C., and a Dean-Stark separator was connected. The mixture was heated and stirred at 150 ° C. in the container, and 1,1-dimethylethanol was removed from the reaction container by the Dean-Stark separator. The reaction mixture was then heated to reflux for 2 hours. The reaction mixture was allowed to cool to near room temperature, concentrated under reduced pressure, ethyl acetate was added to the residue, and the mixture was filtered through Celite (registered trademark). The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography. The obtained 2-fluoro-diphenyl ether was distilled under normal pressure to obtain 22 g of 2-fluoro-diphenyl ether.
2-Fluoro-diphenyl ether
Figure JPOXMLDOC01-appb-C000096
 1 H-NMR (CDCl 3 ) δ: 6.96-7.00 (2H, m), 7.03-7.21 (5H, m), 7.29-7.35 (2H, m).
参考製造例１０
　２－フルオロ－ジフェニルエーテル１４ｇ、Ｎ，Ｎ，Ｎ’，Ｎ”，Ｎ”－ペンタメチルジエチレントリアミン１７ｍｌ及びＴＨＦ２００ｍｌを混合し、－７０℃でｎ－ブチルリチウム１．６モル／リットルのヘキサン溶液４８.５ｍｌを混合し－７０℃で２時間撹拌した。反応混合物にドライアイスを混合後、徐々に室温まで昇温した。減圧下濃縮した後、濃縮液に０℃で反応混合物に５％塩酸を加え、酢酸エチルで抽出した。有機層を飽和食塩水で洗浄後、硫酸マグネシウムで乾燥し、減圧下で濃縮した。得られた残渣を濾取し、ヘキサンで洗浄し、減圧下で乾燥して、２－フルオロ－３－フェノキシベンゼンカルボン酸１５ｇを得た。
　２－フルオロ－３－フェノキシベンゼンカルボン酸
Figure JPOXMLDOC01-appb-C000097
 1H-NMR (CDCl3) δ: 7.00 (2H, d, J = 8.5 Hz), 7.11-7.20 (2H, m), 7.26-7.30 (1H, m), 7.35 (2H, dd, J = 7.9, 7.7 Hz), 7.79 (1H, ddd, J = 7.9, 6.2, 1.5 Hz). Reference production example 10
14 g of 2-fluoro-diphenyl ether, 17 ml of N, N, N ′, N ″, N ″ -pentamethyldiethylenetriamine and 200 ml of THF were mixed, and 48.5 ml of hexane solution of 1.6 mol / liter of n-butyllithium at −70 ° C. Were mixed and stirred at −70 ° C. for 2 hours. After mixing dry ice with the reaction mixture, the temperature was gradually raised to room temperature. After concentration under reduced pressure, 5% hydrochloric acid was added to the reaction mixture at 0 ° C., and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was collected by filtration, washed with hexane, and dried under reduced pressure to obtain 15 g of 2-fluoro-3-phenoxybenzenecarboxylic acid.
2-Fluoro-3-phenoxybenzenecarboxylic acid
Figure JPOXMLDOC01-appb-C000097
 1 H-NMR (CDCl 3 ) δ: 7.00 (2H, d, J = 8.5 Hz), 7.11-7.20 (2H, m), 7.26-7.30 (1H, m), 7.35 (2H, dd, J = 7.9, 7.7 Hz), 7.79 (1H, ddd, J = 7.9, 6.2, 1.5 Hz).
参考製造例１１
　２－フルオロ－３－フェノキシベンゼンカルボン酸１０ｇ、塩化チオニル３.１ｍｌ、ＤＭＦ１滴及びトルエン３０ｍｌの混合物を８０℃で１時間、次いで１１０℃で２時間撹拌した。室温付近まで放冷した反応混合物を減圧下で濃縮し、２－フルオロ－３－フェノキシベンゼンカルボン酸塩化物１１ｇを得た。
　２－フルオロ－３－フェノキシベンゼンカルボン酸塩化物
Figure JPOXMLDOC01-appb-C000098
 1H-NMR (CDCl3) δ: 7.00 (2H, d, J = 8.0 Hz), 7.16 (1H, dd, J = 7.1, 7.1 Hz), 7.22 (1H, td, J = 8.2, 1.0 Hz), 7.30-7.39 (3H, m), 7.84 (1H, ddd, J = 7.8, 6.2, 1.5 Hz). Reference production example 11
A mixture of 10 g of 2-fluoro-3-phenoxybenzenecarboxylic acid, 3.1 ml of thionyl chloride, 1 drop of DMF and 30 ml of toluene was stirred at 80 ° C. for 1 hour and then at 110 ° C. for 2 hours. The reaction mixture was allowed to cool to near room temperature and concentrated under reduced pressure to obtain 11 g of 2-fluoro-3-phenoxybenzenecarboxylic acid chloride.
2-Fluoro-3-phenoxybenzenecarboxylic acid chloride
Figure JPOXMLDOC01-appb-C000098
 1 H-NMR (CDCl 3 ) δ: 7.00 (2H, d, J = 8.0 Hz), 7.16 (1H, dd, J = 7.1, 7.1 Hz), 7.22 (1H, td, J = 8.2, 1.0 Hz), 7.30-7.39 (3H, m), 7.84 (1H, ddd, J = 7.8, 6.2, 1.5 Hz).
参考製造例１２
　２８％アンモニア水２０ｍｌ及びＴＨＦ５０ｍｌの混合物に、０℃で２－フルオロ－３－フェノキシベンゼンカルボン酸塩化物を滴下し、室温で1時間攪拌した。反応混合物を減圧下で濃縮し、得られた残渣を濾取した。水及びヘキサンで洗浄し、減圧下で乾燥して、２－フルオロ－３－フェノキシベンズアミド８.９ｇを得た。
　２－フルオロ－３－フェノキシベンズアミド
Figure JPOXMLDOC01-appb-C000099
 1H-NMR (CDCl3) δ: 6.06 (1H, s), 6.64 (1H, s), 7.00 (2H, d, J = 7.2 Hz), 7.12-7.27 (3H, m), 7.36 (2H, t, J = 7.0 Hz), 7.85-7.89 (1H, m). Reference production example 12
To a mixture of 20% 28% aqueous ammonia and 50 ml of THF, 2-fluoro-3-phenoxybenzenecarboxylic acid chloride was added dropwise at 0 ° C., and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the resulting residue was collected by filtration. Washing with water and hexane and drying under reduced pressure gave 8.9 g of 2-fluoro-3-phenoxybenzamide.
2-Fluoro-3-phenoxybenzamide
Figure JPOXMLDOC01-appb-C000099
 1 H-NMR (CDCl 3 ) δ: 6.06 (1H, s), 6.64 (1H, s), 7.00 (2H, d, J = 7.2 Hz), 7.12-7.27 (3H, m), 7.36 (2H, t , J = 7.0 Hz), 7.85-7.89 (1H, m).
参考製造例１３
　水酸化ナトリウム２．７１ｇを水４５ｍｌに溶解し、ここに－１０℃で臭素１．２ｍｌ及び２－フルオロ－３－フェノキシベンズアミド４．４８ｇを順次混合した。この混合物を０℃で３０分間、次いで７０℃で６時間撹拌した。室温付近まで放冷した反応混合物に氷水を加え、酢酸エチルで抽出した。有機層を飽和炭酸水素ナトリウム水溶液及び水で順次洗浄した後、硫酸マグネシウムで乾燥し、減圧下濃縮した。得られた残渣をシリカゲルカラムクロマトグラフィーに付して２－フルオロ－３－フェノキシアニリン２．４３ｇを得た。
　２－フルオロ－３－フェノキシアニリン
Figure JPOXMLDOC01-appb-C000100
 1H-NMR (CDCl3) δ: 3.80 (2H, s), 6.39-6.43 (1H, m), 6.57 (1H, td, J = 7.9, 1.5 Hz), 6.86 (1H, td, J = 8.1, 1.8 Hz), 6.98-7.02 (2H, m), 7.06-7.10 (1H, m), 7.29-7.34 (2H, m) Reference production example 13
2.71 g of sodium hydroxide was dissolved in 45 ml of water, and 1.2 ml of bromine and 4.48 g of 2-fluoro-3-phenoxybenzamide were sequentially mixed at −10 ° C. The mixture was stirred at 0 ° C. for 30 minutes and then at 70 ° C. for 6 hours. Ice water was added to the reaction mixture which was allowed to cool to around room temperature, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with a saturated aqueous sodium hydrogen carbonate solution and water, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was subjected to silica gel column chromatography to obtain 2.43 g of 2-fluoro-3-phenoxyaniline.
2-Fluoro-3-phenoxyaniline
Figure JPOXMLDOC01-appb-C000100
 1 H-NMR (CDCl 3 ) δ: 3.80 (2H, s), 6.39-6.43 (1H, m), 6.57 (1H, td, J = 7.9, 1.5 Hz), 6.86 (1H, td, J = 8.1, 1.8 Hz), 6.98-7.02 (2H, m), 7.06-7.10 (1H, m), 7.29-7.34 (2H, m)
　次に製剤例を示す。なお、部は重量部を表す。 Next, formulation examples are shown. In addition, a part represents a weight part.
製剤例１
　本発明化合物１～本発明化合物７７のいずれか1種 ５０部、リグニンスルホン酸カルシウム ３部、ラウリル硫酸マグネシウム ２部及び合成含水酸化珪素 ４５部をよく粉砕混合することにより、水和剤を得る。 Formulation Example 1
A wettable powder is obtained by thoroughly pulverizing and mixing 50 parts of any one of the present compounds 1 to 77, 3 parts of calcium lignin sulfonate, 2 parts of magnesium lauryl sulfate and 45 parts of synthetic hydrous hydroxide.
製剤例２
　本発明化合物１～本発明化合物７７のいずれか1種 ２０部とソルビタントリオレエ－ト １．５部とを、ポリビニルアルコ－ル ２部を含む水溶液 ２８．５部と混合し、湿式粉砕法で微粉砕した後、この中に、キサンタンガム ０．０５部及びアルミニウムマグネシウムシリケ－ト ０．１部を含む水溶液 ４０部を加え、さらにプロピレングリコ－ル １０部を加えて攪拌混合し、フロアブル製剤を得る。 Formulation Example 2
20 parts of any one of compounds 1 to 77 of the present invention and 1.5 parts of sorbitan trioleate are mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol, and wet pulverization is used. After finely pulverizing, 40 parts of an aqueous solution containing 0.05 part of xanthan gum and 0.1 part of aluminum magnesium silicate is added thereto, and further 10 parts of propylene glycol is added and mixed by stirring to obtain a flowable preparation. obtain.
製剤例３
　本発明化合物１～本発明化合物７７のいずれか1種 ２部、カオリンクレー ８８部及びタルク １０部をよく粉砕混合することにより、粉剤を得る。 Formulation Example 3
A powder is obtained by thoroughly pulverizing and mixing 2 parts of the present compound 1 to the present compound 77, 88 parts of kaolin clay and 10 parts of talc.
製剤例４
　本発明化合物１～本発明化合物７７のいずれか1種 ５部、ポリオキシエチレンスチリルフェニルエ－テル １４部、ドデシルベンゼンスルホン酸カルシウム ６部及びキシレン ７５部をよく混合することにより、乳剤を得る。 Formulation Example 4
An emulsion is obtained by thoroughly mixing 5 parts of any one of the present compounds 1 to 77, 14 parts of polyoxyethylene styrylphenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 75 parts of xylene.
製剤例５
　本発明化合物１～本発明化合物７７のいずれか1種 ２部、合成含水酸化珪素 １部、リグニンスルホン酸カルシウム ２部、ベントナイト ３０部及びカオリンクレー ６５部をよく粉砕混合した後、水を加えてよく練り合せ、造粒乾燥することにより、粒剤を得る。 Formulation Example 5
After thoroughly mixing 2 parts of any one of the present compounds 1 to 77, 1 part of synthetic hydrous silicon oxide, 2 parts of calcium lignin sulfonate, 30 parts of bentonite and 65 parts of kaolin clay, water is added. Granules are obtained by kneading well and granulating and drying.
製剤例６
　本発明化合物１～本発明化合物７７のいずれか1種 １０部、ポリオキシエチレンアルキルエーテルサルフェートアンモニウム塩 ５０部を含むホワイトカーボン ３５部及び水 ５５部を混合し、湿式粉砕法で微粉砕することにより、フロアブル製剤を得る。 Formulation Example 6
By mixing 10 parts of any one of compounds 1 to 77 of the present invention, 35 parts of white carbon containing 50 parts of polyoxyethylene alkyl ether sulfate ammonium salt, and 55 parts of water, and finely pulverizing them by a wet pulverization method. Get a flowable formulation.
製剤例７
　本発明化合物１～本発明化合物７７のいずれか1種を４０部、プロピレングリコールを５部（ナカライテスク製）、Soprophor FLK を５部（ローディア日華製）、アンチフォームCエマルションを０．２部（ダウコーニング社製）、プロキセルGXLを ０．３部（アーチケミカル製）、イオン交換水を４９．５部の割合で混合し、原体スラリーを調製する。該スラリー１００部に１５０部のガラスビーズ（Φ=1mm）を投入し、冷却水で冷却しながら、２時間粉砕する。粉砕後、ガラスビーズを除去し、本発明化合物１の含量が４０重量％のフロアブル製剤を得る。 Formulation Example 7
40 parts of any one of the present compounds 1 to 77, 5 parts of propylene glycol (manufactured by Nacalai Tesque), 5 parts of Soprophor FLK (manufactured by Rhodia Nikka), 0.2 part of anti-form C emulsion (Dow Corning), 0.3 parts of Proxel GXL (manufactured by Arch Chemical Co., Ltd.) and 49.5 parts of ion-exchanged water are mixed to prepare a base slurry. 150 parts of glass beads (Φ = 1 mm) are put into 100 parts of the slurry, and pulverized for 2 hours while cooling with cooling water. After pulverization, the glass beads are removed to obtain a flowable preparation having a content of Compound 1 of the present invention of 40% by weight.
製剤例８
　本発明化合物１～本発明化合物７７のいずれか1種を５０部、NNカオリンクレーを３８．５部（竹原化学工業製）、Morwet D４２５を１０部、Morwer EFWを１．５部（アクゾノーベル社製）の割合で混合し、AIプレミックスを得る。当プレミックスをジェットミルで粉砕し、粉剤を得る。 Formulation Example 8
50 parts of any one of compounds 1 to 77 of the present invention, 38.5 parts of NN kaolin clay (manufactured by Takehara Chemical Industries), 10 parts of Morwet D425, 1.5 parts of Morwer EFW (Akzo Nobel) To make an AI premix. The premix is pulverized with a jet mill to obtain a powder.
　次に、本発明化合物が植物病害の防除に有用であることを試験例で示す。
　なお防除効果は、調査時の供試植物上の病斑の面積を目視観察し、本発明化合物を処理
した植物の病斑の面積と、無処理の植物の病斑の面積を比較することにより評価した。 Next, test examples show that the compounds of the present invention are useful for controlling plant diseases.
The control effect is obtained by visually observing the area of the lesion on the test plant at the time of the survey, and comparing the area of the lesion on the plant treated with the compound of the present invention and the area of the lesion on the untreated plant. evaluated.
　なお対照として、国際公開第２００５／０３３０７９号パンフレットの実施例Ｚ－２に記載の下式（Ａ）で示される化合物（以下、比較化合物（Ａ）と記す。）
Figure JPOXMLDOC01-appb-C000101
 及び、
下式（Ｂ）で示される化合物（以下、比較化合物（Ｂ）と記す。）
Figure JPOXMLDOC01-appb-C000102
 をあわせて試験に供試した。 As a control, a compound represented by the following formula (A) described in Example Z-2 of WO 2005/033079 pamphlet (hereinafter referred to as comparative compound (A))
Figure JPOXMLDOC01-appb-C000101
 as well as,
Compound represented by the following formula (B) (hereinafter referred to as comparative compound (B))
Figure JPOXMLDOC01-appb-C000102
 Were used in the test.
試験例１；
　プラスチックポットに砂壌土を詰め、イネ（品種；日本晴）を播種し、温室内で２０日間生育させた。その後、本発明化合物１～７７、比較化合物（Ａ）及び比較化合物（Ｂ）の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度（５００ｐｐｍ）にし、上記イネの葉面に充分付着するように茎葉散布した。散布後、植物を風乾し、昼間２４℃、夜間２０℃多湿下で、イネいもち病菌（Ｍａｇｎａｐｏｒｔｈｅ　ｇｒｉｓｅａ）に罹病したイネ苗（品種；日本晴）と接触させながら６日間置いた後、病斑面積を調査した。その結果、本発明化合物２２、２４、３０、３１、５０、５９、６１、６４、７７を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。 Test Example 1;
A plastic pot was filled with sand loam, seeded with rice (variety: Nipponbare), and grown in a greenhouse for 20 days. Thereafter, each of the present compounds 1 to 77, the comparative compound (A) and the comparative compound (B) was made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm). The foliage was sprayed so as to adhere well to the surface. After spraying, the plants were air-dried and placed for 6 days in contact with rice seedlings (variety: Nihonbare) afflicted with rice blast fungus (Magnaporthe grisea) at 24 ° C in the daytime and 20 ° C in the nighttime at high humidity. investigated. As a result, the lesion area in the plant which processed this invention compound 22, 24, 30, 31, 50, 59, 61, 64, 77 was 30% or less of the lesion area in an untreated plant.
試験例２；
　プラスチックポットに砂壌土を詰め、キュウリ（品種；相模半白）を播種し、温室内で１２日間生育させた。本発明化合物１～７７、比較化合物（Ａ）及び比較化合物（Ｂ）の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度（５００ｐｐｍ）にし、上記キュウリ葉面に充分付着するように茎葉散布した。散布後植物を風乾し、キュウリ灰色かび病菌（Ｂｏｔｒｙｔｉｓ　ｃｉｎｅｒｅａ）の胞子含有ＰＤＡ培地をキュウリ葉面上に置いた。接種後１２℃、多湿下に5日間置いた後、病斑面積を調査した。その結果、本発明化合物１、３、９、２４、２６、４７、５１、６０、６１、６２、６４、６５、６７、７４、７５、７７を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。比較化合物（Ａ）及び比較化合物（Ｂ）を供試した植物上の病斑面積は、無処理区の病斑面積の７６～１００％であった。 Test Example 2;
A plastic pot was filled with sandy loam, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days. Each of the compounds 1 to 77 of the present invention, the comparative compound (A) and the comparative compound (B) was made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm), which was sufficient for the cucumber leaf surface. The foliage was sprayed to adhere. After spraying, the plants were air-dried, and a spore-containing PDA medium of Botrytis cinerea was placed on the cucumber leaf surface. After inoculation, the lesion area was examined after 5 days in a humid environment at 12 ° C. As a result, the lesion area in the plant treated with the compound 1, 3, 9, 24, 26, 47, 51, 60, 61, 62, 64, 65, 67, 74, 75, 77 of the present invention was untreated. It was 30% or less of the lesion area in the plant. The lesion area on the plants on which the comparative compound (A) and the comparative compound (B) were tested was 76 to 100% of the lesion area in the untreated group.
試験例３；
　プラスチックポットに砂壌土を詰め、コムギ（品種；シロガネ）を播種し、温室内で９日間生育させた。本発明化合物１９～７７の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度(５００ｐｐｍ)にし、上記コムギの葉面に充分付着するように茎葉散布した。散布後植物を風乾し、１８℃、照明下で５日間栽培した後、コムギ赤さび病菌（Ｐｕｃｃｉｎｉａ　ｒｅｃｏｎｄｉｔａ）の胞子をふりかけ接種した。接種後２３℃、暗黒多湿下に１日置いた後、１８℃、照明下で１０日間栽培し、病斑面積を調査した。その結果、本発明化合物２０、５５を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。 Test Example 3;
A plastic pot was stuffed with sand loam, seeded with wheat (variety: Shirogane), and grown in a greenhouse for 9 days. Each of the compounds 19 to 77 of the present invention was made into a flowable formulation according to Formulation Example 6, diluted with water to a predetermined concentration (500 ppm), and sprayed with foliage so that it was sufficiently attached to the leaf surface of the wheat. After spraying, the plants were air-dried and cultivated under illumination at 18 ° C. for 5 days, and then inoculated with spores of wheat red rust fungus (Puccinia recondita). After inoculation at 23 ° C. for 1 day under dark and humid conditions, the plant was cultivated under illumination at 18 ° C. for 10 days, and the lesion area was examined. As a result, the lesion area in the plant treated with the present compounds 20, 55 was 30% or less of the lesion area in the untreated plant.
試験例４；
　プラスチックポットに砂壌土を詰め、キュウリ（品種；相模半白）を播種し、温室内で
１２日間生育させた。本発明化合物１～７７、比較化合物（Ａ）及び比較化合物（Ｂ）の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度（５００ｐｐｍ）にし、上記キュウリ葉面に充分付着するように茎葉散布した。散布後植物を風乾し、菌核病菌（Ｓｃｌｅｒｏｔｉｎｉａ　ｓｃｌｅｒｏｔｉｏｒｕｍ）の菌糸含有ＰＤＡ培地をキュウリ葉面上に置いた。接種後１８℃、多湿下に４日間置いた後、病斑面積を調査した。その結果、本発明化合物１～７、９～１３、１５～２４、２６～５４、５６～７７、比較化合物（Ａ）を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。 Test Example 4;
A plastic pot was filled with sandy loam, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days. Each of the compounds 1 to 77 of the present invention, the comparative compound (A) and the comparative compound (B) was made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm), which was sufficient for the cucumber leaf surface. The foliage was sprayed to adhere. After spraying, the plant was air-dried, and a mycelia-containing PDA medium of Sclerotinia sclerotiorum was placed on the cucumber leaf surface. After the inoculation, the lesion area was examined after being placed at 18 ° C. under high humidity for 4 days. As a result, the lesion area in the plant treated with the present compounds 1-7, 9-13, 15-24, 26-54, 56-77 and the comparative compound (A) is the lesion area in the untreated plant. It was 30% or less.
試験例５；
　プラスチックポットに砂壌土を詰め、キュウリ（品種；相模半白）を播種し、温室内で１２日間生育させた。本発明化合物１～７７、比較化合物（Ａ）及び比較化合物（Ｂ）の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度（５００ｐｐｍ）にし、上記キュウリ葉面に充分付着するように茎葉散布した。散布後植物を風乾し、キュウリうどんこ病菌（Ｓｐｈａｅｒｏｔｈｅｃａ　ｆｕｌｉｇｉｎｅａ）胞子の水懸濁液を噴霧接種した。昼間２４℃、夜間２０℃の温室で１２日栽培した後、病斑面積を調査した。その結果、本発明化合物２４、６０を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。 Test Example 5;
A plastic pot was filled with sandy loam, cucumber (variety: Sagamihanjiro) was sown and grown in a greenhouse for 12 days. Each of the compounds 1 to 77 of the present invention, the comparative compound (A) and the comparative compound (B) was made into a flowable formulation according to Formulation Example 6 and then diluted with water to a predetermined concentration (500 ppm), which was sufficient for the cucumber leaf surface. The foliage was sprayed to adhere. After spraying, the plants were air-dried and spray-inoculated with an aqueous suspension of Sphaerotheca furiginea spores. After cultivating in a greenhouse at 24 ° C during the daytime and 20 ° C during the nighttime, the lesion area was examined. As a result, the lesion area in the plant treated with the compounds 24 and 60 of the present invention was 30% or less of the lesion area in the untreated plant.
試験例６；
　プラスチックポットに砂壌土を詰め、コムギ（品種；アポジー）を播種し、温室内で１０日間生育させた。本発明化合物２２～７７の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度（５００ｐｐｍ）にし、上記コムギの葉面に充分付着するように茎葉散布した。散布後植物を風乾し、２日後にコムギ葉枯病菌（Ｓｅｐｔｏｒｉａ　ｔｒｉｔｉｃｉ）胞子の水懸濁液を噴霧接種した。接種後はじめは１８℃多湿下に３日置き、さらに照明下に１４日から１８日間置いた後、病斑面積を調査した。その結果、本発明化合物２４、２６、２７、５６、５９、６０、６４、６５を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。 Test Example 6;
A plastic pot was filled with sandy loam, wheat (cultivar: Apogee) was sown and grown in a greenhouse for 10 days. Each of the compounds 22 to 77 of the present invention was made into a flowable formulation according to Formulation Example 6, diluted with water to a predetermined concentration (500 ppm), and sprayed with foliage so as to adhere well to the leaf surface of the wheat. After spraying, the plants were air-dried, and after 2 days, sprayed with a water suspension of Septoria tritici spores. After the inoculation, the area was first placed under high humidity at 18 ° C. for 3 days and further under illumination for 14 to 18 days, and then the lesion area was examined. As a result, the lesion area in the plant treated with the present compounds 24, 26, 27, 56, 59, 60, 64, 65 was 30% or less of the lesion area in the untreated plant.
試験例７；
　プラスチックポットに砂壌土を詰め、ブドウ（品種；ベリーＡの実生）を播種し、温室内で４０日間生育させた。上記ポットにブドウべと病菌遊走子嚢の水懸濁液を噴霧接種し、２３℃、多湿下に１日間置いた後、風乾し、ブドウべと病（Ｐｌａｓｍｏｐａｒａ　ｖｉｔｉｃｏｌａ）感染苗とした。本発明化合物１～７０、比較化合物（Ａ）及び比較化合物（Ｂ）の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し所定濃度(５００ppm)にし、上記ブドウ苗の葉面に充分付着するように茎葉散布した。散布後、植物を風乾し、２３℃の温室内で５日間置き、さらに２３℃多湿下に１日間置いた後、病斑面積を調査した。その結果、本発明化合物１５を処理した植物における病斑面積は、無処理の植物における病斑面積の３０％以下であった。 Test Example 7;
A plastic pot was filled with sand loam, sown with grapes (variety: seedlings of berry A), and grown in a greenhouse for 40 days. The above-mentioned pot was spray-inoculated with a water suspension of grape mildew zoosporangium, placed at 23 ° C. under high humidity for 1 day, and then air-dried to obtain a seedling infected with grape mildew (Plasmopara viticola). Each of the compounds 1 to 70 of the present invention, the comparative compound (A) and the comparative compound (B) is made into a flowable preparation according to Preparation Example 6, and then diluted with water to a predetermined concentration (500 ppm). The foliage was sprayed so as to adhere well. After spraying, the plants were air-dried, placed in a 23 ° C. greenhouse for 5 days, and further placed at 23 ° C. and humid for 1 day, and then the lesion area was examined. As a result, the lesion area in the plant treated with the compound 15 of the present invention was 30% or less of the lesion area in the untreated plant.
試験例８；
　プラスチックポットにトマト萎凋病（Ｆｕｓａｒｉｕｍ　ｏｘｙｓｐｏｒｕｍ）汚染土壌を詰め、トマト（品種：パティオ）を播種し、本発明化合物１～７７の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し上記プラスチックポットあたり１０ｍｇの化合物を土壌灌注処理する。温室内で１ヶ月間栽培した後、無処理の植物と比較する。その結果、本発明化合物１～７７を処理した植物は病斑が認められず非汚染土壌で生育した植物と同等の良好な生育が認められる。 Test Example 8;
A plastic pot is filled with Fusarium oxysporum contaminated soil, seeded with tomato (variety: patio), each of the present compounds 1 to 77 is made into a flowable formulation according to Formulation Example 6, and then diluted with water. 10 mg of compound per soil pot is soil irrigated. After growing in a greenhouse for 1 month, compare with untreated plants. As a result, the plants treated with the compounds 1 to 77 of the present invention have no lesions, and the same good growth as that of plants grown on non-contaminated soil is observed.
試験例９；
　プラスチックポットにジャガイモ半身萎凋病（Ｖｅｒｔｉｃｉｌｌｉｕｍ　ａｌｂｏ-ａｔｒｕｍ，　ｖ．　ｄａｈｌｉａｅ，　ｖ．　ｎｉｇｒｅｓｃｅｎｓ）汚染土壌を詰め、ジャガイモ（品種：男爵）を植付け、本発明化合物１～７７の各々を製剤例６に準じてフロアブル製剤とした後、水で希釈し上記プラスチックポットあたり１０ｍｇの化合物を土壌灌注処理する。温室内で２ヶ月間栽培した後、無処理の植物と比較する。その結果、本発明化合物１～７７を処理した植物は病斑が認められず非汚染土壌で生育した植物と同等の良好な生育が認められる。 Test Example 9;
A plastic pot is filled with soil contaminated with potato half body wilt (Verticillium albo-atrum, v. Dahliae, v. Nigrescens), potatoes (variety: baron) are planted, and each of the compounds 1 to 77 of the present invention is prepared according to Formulation Example 6. After making the flowable formulation, the mixture is diluted with water and 10 mg of the compound per soil pot is soil irrigated. After growing in a greenhouse for 2 months, compare with untreated plants. As a result, the plants treated with the compounds 1 to 77 of the present invention have no lesions, and the same good growth as that of plants grown on non-contaminated soil is observed.
試験例１０；
　本発明化合物１～７７の各々を製剤例６に準じてフロアブル製剤とした後、イネ馬鹿苗病菌（Ｇｉｂｂｅｒｅｌｌａ　ｆｕｊｉｋｕｒｏｉ）汚染籾に１００ｋｇ種子あたり２００ｇの化合物を種子処理する。その後、温室内で１ヶ月間栽培した後、無処理の植物と比較する。その結果、本発明化合物１～７７を処理した植物には非汚染籾から生育した植物と同等の良好な生育が認められる。 Test Example 10;
Each of the compounds 1 to 77 of the present invention is made into a flowable formulation according to Formulation Example 6, and then 200 g of the compound per 100 kg seed is treated with a rice-fouling fungus (Gibberella fujikuroi) contaminated pod. Then, after cultivating for 1 month in a greenhouse, it compares with an untreated plant. As a result, the plants treated with the compounds 1 to 77 of the present invention have good growth equivalent to the plants grown from non-contaminated cocoons.
試験例１１；
　本発明化合物１～７７の各々を製剤例６に準じてフロアブル製剤とした後、ムギ立枯病菌（Ｇａｅｕｍａｎｎｏｍｙｃｅｓ　ｇｒａｍｉｎｉｓ）汚染種子に１００ｋｇ種子あたり２００ｇの化合物を種子処理する。その後、温室内で１ヶ月間栽培した後、無処理の植物と比較する。その結果、本発明化合物１～７７を処理した植物には非汚染種子から生育した植物と同等の良好な生育が認められる。 Test Example 11;
Each of the compounds 1 to 77 of the present invention is made into a flowable formulation according to Formulation Example 6, and then 200 g of the compound per 100 kg seed is treated with seeds contaminated with Gaeumanomyces graminis. Then, after cultivating for 1 month in a greenhouse, it compares with an untreated plant. As a result, the plants treated with the compounds 1 to 77 of the present invention show good growth equivalent to plants grown from non-contaminated seeds.
試験例１２；
　本発明化合物１～７７の各々を製剤例７に準じてフロアブル製剤とした後、イネ馬鹿苗病菌（Ｇｉｂｂｅｒｅｌｌａ　ｆｕｊｉｋｕｒｏｉ）汚染籾に１００ｋｇ種子あたり２００ｇの化合物を種子処理する。その後、温室内で１ヶ月間栽培した後、無処理の植物と比較する。その結果、本発明化合物１～７７を処理した植物には非汚染籾から生育した植物と同等の良好な生育が認められる。 Test Example 12;
Each of the compounds 1 to 77 of the present invention is made into a flowable formulation according to Formulation Example 7, and then 200 g of the compound per 100 kg seed is seed-treated in rice stagnation fungus (Gibberella fujikuroi) contaminated pods. Then, after cultivating for 1 month in a greenhouse, it compares with an untreated plant. As a result, the plants treated with the compounds 1 to 77 of the present invention have good growth equivalent to the plants grown from non-contaminated cocoons.
試験例１３；
　本発明化合物１～７７の各々を製剤例７に準じてフロアブル製剤とした後、ムギ立枯病菌（Ｇａｅｕｍａｎｎｏｍｙｃｅｓ　ｇｒａｍｉｎｉｓ）汚染種子に１００ｋｇ種子あたり２００ｇの化合物を種子処理する。その後、温室内で１ヶ月間栽培した後、無処理の植物と比較する。その結果、本発明化合物１～７７を処理した植物には非汚染種子から生育した植物と同等の良好な生育が認められる。 Test Example 13;
Each of the compounds 1 to 77 of the present invention is made into a flowable formulation according to Formulation Example 7, and then 200 g of the compound per 100 kg seed is treated with seeds contaminated with Gaeumanomyces graminis. Then, after cultivating for 1 month in a greenhouse, it compares with an untreated plant. As a result, the plants treated with the compounds 1 to 77 of the present invention show good growth equivalent to plants grown from non-contaminated seeds.

Claims (21)

  1. 　式（Ｉ）
    Figure JPOXMLDOC01-appb-C000001
     〔式中、
    Ａは、６－キノリル基、ベンゾチアゾール－６－イル基又は［１，５］ナフチリジン－２－イル基を表し、
    ｎは、０～４の整数のいずれかを表し、
    Ｒ１は、ハロゲン原子又はＣ１－Ｃ３アルキル基を表し、
    Ｒ２は、ベンゼン環の３位又は４位に置換した、Ｃ１－Ｃ８アルキル基、Ｃ１－Ｃ８アルコキシ基、Ｃ３－Ｃ９アルケニルオキシ基、Ｃ３－Ｃ９アルキニルオキシ基、Ｃ６－Ｃ１０アリールオキシ基又は（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルコキシ基を表す。
    ここで、該Ｒ２で示されるＣ１－Ｃ８アルキル基、Ｃ１－Ｃ８アルコキシ基、Ｃ３－Ｃ９アルケニルオキシ基、Ｃ３－Ｃ９アルキニルオキシ基及び（Ｃ３－Ｃ８シクロアルキル）Ｃ１－Ｃ６アルコキシ基は、ハロゲン原子及びＣ１－Ｃ３アルコキシ基からなる群より選ばれる１以上の基で置換されていてもよく、
    また、該Ｒ２で示されるＣ６－Ｃ１０アリールオキシ基は、ハロゲン原子、Ｃ１－Ｃ３アルキル基、Ｃ１－Ｃ３アルコキシ基及びトリフルオロメチル基からなる群より選ばれる１以上の基で置換されていてもよく、
    但し、ｎが０であり、Ｒ２がベンゼン環の３位に置換したトリフルオロメチル基である場合、Ａはベンゾチアゾール－６－イル基又は［１，５］ナフチリジン－２－イル基を表し、
    ｎが２、３又は４である場合、Ｒ１は互いに同一又は相異なる。〕で示されるアニリド化合物。     Formula (I)
    Figure JPOXMLDOC01-appb-C000001
     [Where,
    A represents a 6-quinolyl group, a benzothiazol-6-yl group or a [1,5] naphthyridin-2-yl group;
    n represents an integer of 0 to 4,
    R 1 represents a halogen atom or a C1-C3 alkyl group,
    R 2 represents a C1-C8 alkyl group, a C1-C8 alkoxy group, a C3-C9 alkenyloxy group, a C3-C9 alkynyloxy group, a C6-C10 aryloxy group substituted at the 3-position or 4-position of the benzene ring, or ( C3-C8 cycloalkyl) represents a C1-C6 alkoxy group.
    Here, the C1-C8 alkyl group, C1-C8 alkoxy group, C3-C9 alkenyloxy group, C3-C9 alkynyloxy group and (C3-C8 cycloalkyl) C1-C6 alkoxy group represented by R 2 are halogenated. May be substituted with one or more groups selected from the group consisting of atoms and C1-C3 alkoxy groups,
    The C6-C10 aryloxy group represented by R 2 is substituted with one or more groups selected from the group consisting of a halogen atom, a C1-C3 alkyl group, a C1-C3 alkoxy group and a trifluoromethyl group. Well,
    However, when n is 0 and R 2 is a trifluoromethyl group substituted at the 3-position of the benzene ring, A represents a benzothiazol-6-yl group or a [1,5] naphthyridin-2-yl group. ,
    When n is 2, 3 or 4, R 1 is the same or different from each other. ] The anilide compound shown by this.
  2. 　Ａが、６－キノリル基である請求項１記載のアニリド化合物。 The anilide compound according to claim 1, wherein A is a 6-quinolyl group.
  3. 　Ｒ２の置換位置がベンゼン環の３位である請求項１又は２記載のアニリド化合物。 The anilide compound according to claim 1 or 2, wherein the substitution position of R 2 is the 3-position of the benzene ring.
  4. 　Ａが６－キノリル基であり、ｎが１であり、Ｒ１がベンゼン環の２位に置換したフッ素原子であり、Ｒ２がベンゼン環の３位に置換したメトキシ基である請求項１記載のアニリド化合物。 2. A is a 6-quinolyl group, n is 1, R 1 is a fluorine atom substituted at the 2-position of the benzene ring, and R 2 is a methoxy group substituted at the 3-position of the benzene ring. Anilide compound.
  5. ３’－（４－ペンチニルオキシ）－キノリン－６－カルボン酸アニリド。 3 '-(4-pentynyloxy) -quinoline-6-carboxylic acid anilide.
  6. ３’－ブチルオキシ－キノリン－６－カルボン酸アニリド。 3'-Butyloxy-quinoline-6-carboxylic acid anilide.
  7. ３’－（２－ペンテニルオキシ）－キノリン－６－カルボン酸アニリド。 3 '-(2-pentenyloxy) -quinoline-6-carboxylic acid anilide.
  8. ３’－（４－ペンテニルオキシ）－キノリン－６－カルボン酸アニリド。 3 '-(4-Pentenyloxy) -quinoline-6-carboxylic acid anilide.
  9. ２’－フルオロ－３’－（４－ペンチニルオキシ）－キノリン－６－カルボン酸アニリド。 2'-Fluoro-3 '-(4-pentynyloxy) -quinoline-6-carboxylic acid anilide.
  10. ２’－フルオロ－３’－（４－ペンテニルオキシ）－キノリン－６－カルボン酸アニリド。 2'-Fluoro-3 '-(4-pentenyloxy) -quinoline-6-carboxylic acid anilide.
  11. ２’－フルオロ－３’－（５－ヘキセニルオキシ）－キノリン－６－カルボン酸アニリド。 2'-Fluoro-3 '-(5-hexenyloxy) -quinoline-6-carboxylic acid anilide.
  12. ２’－フルオロ－３’－（５－ヘキシニルオキシ）－キノリン－６－カルボン酸アニリド。 2'-Fluoro-3 '-(5-hexynyloxy) -quinoline-6-carboxylic acid anilide.
  13. ２’－フルオロ－３’－（２－メチル－プロピルオキシ）－キノリン－６－カルボン酸アニリド。 2'-Fluoro-3 '-(2-methyl-propyloxy) -quinoline-6-carboxylic acid anilide.
  14. ２’－フルオロ－３’－（２－ブチニルオキシ）キノリン－６－カルボン酸アニリド。 2'-Fluoro-3 '-(2-butynyloxy) quinoline-6-carboxylic acid anilide.
  15. ２’－フルオロ－３’－（３－エトキシプロピルオキシ）キノリン－６－カルボン酸アニリド。 2'-Fluoro-3 '-(3-ethoxypropyloxy) quinoline-6-carboxylic acid anilide.
  16. ２’－フルオロ－３’－（２－プロペニルオキシ）－キノリン－６－カルボン酸アニリド。 2'-Fluoro-3 '-(2-propenyloxy) -quinoline-6-carboxylic acid anilide.
  17. ２’－フルオロ－３’－エトキシ－キノリン－６－カルボン酸アニリド。 2'-Fluoro-3'-ethoxy-quinoline-6-carboxylic acid anilide.
  18. ２’－フルオロ－３’－ブトキシ－キノリン－６－カルボン酸アニリド。 2'-Fluoro-3'-butoxy-quinoline-6-carboxylic acid anilide.
  19. 　請求項１記載のアニリド化合物を含有する植物病害防除剤。 A plant disease control agent comprising the anilide compound according to claim 1.
  20. 　請求項１記載のアニリド化合物の有効量を植物又は土壌に施用する工程を有する植物病害の防除方法。 A method for controlling plant diseases comprising a step of applying an effective amount of the anilide compound according to claim 1 to a plant or soil.
  21. 　植物病害を防除するための請求項１記載のアニリド化合物の使用。 Use of the anilide compound according to claim 1 for controlling plant diseases.
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JP2013112618A (en) * 2011-11-25 2013-06-10 Nippon Kayaku Co Ltd 1,5-naphthyridine derivative, and insecticide containing the same as active ingredient
CN118184577A (en) * 2024-05-17 2024-06-14 山东省农药科学研究院 Phenyl ether meta-amide compound and application thereof

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