WO2024101172A1 - (hetero)aryl urea compound and insecticide - Google Patents

(hetero)aryl urea compound and insecticide Download PDF

Info

Publication number
WO2024101172A1
WO2024101172A1 PCT/JP2023/038749 JP2023038749W WO2024101172A1 WO 2024101172 A1 WO2024101172 A1 WO 2024101172A1 JP 2023038749 W JP2023038749 W JP 2023038749W WO 2024101172 A1 WO2024101172 A1 WO 2024101172A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
added
trifluoromethyl
compound
triazol
Prior art date
Application number
PCT/JP2023/038749
Other languages
French (fr)
Japanese (ja)
Inventor
史也 西尾
聖 牧野
衆一 伊藤
理奈 矢田
昌宏 川口
Original Assignee
日本曹達株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 日本曹達株式会社 filed Critical 日本曹達株式会社
Publication of WO2024101172A1 publication Critical patent/WO2024101172A1/en

Links

Classifications

    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/30—Derivatives containing the group >N—CO—N aryl or >N—CS—N—aryl
    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/36—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the group >N—CO—N< directly attached to at least one heterocyclic ring; Thio analogues thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P7/00—Arthropodicides
    • A01P7/04—Insecticides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • the present invention relates to a (hetero)aryl urea compound and an insecticide. More specifically, the present invention relates to a (hetero)aryl urea compound that has excellent insecticidal activity, is safe, and can be synthesized industrially advantageously, and to an insecticide containing the same as an active ingredient.
  • This application claims priority based on Japanese Patent Application No. 2022-180255, filed on November 10, 2022, the contents of which are incorporated herein by reference.
  • Patent Document 1 teaches that the compound represented by formula (P1) can be used as an insecticide.
  • the object of the present invention is to provide a (hetero)aryl urea compound that has excellent insecticidal activity, is safe, and can be synthesized industrially in an advantageous manner, and an insecticide that contains the compound as an active ingredient.
  • a 1 represents a nitrogen atom or a group represented by CH;
  • R 1 represents a C1-6 haloalkoxy group or a C1-6 haloalkylthio group;
  • R a represents a hydrogen atom or a substituted or unsubstituted C3-6 cycloalkyl group;
  • B1 represents a nitrogen atom or a group represented by CH;
  • B2 represents a nitrogen atom or a group represented by CXb ;
  • Xa and Xb each independently represent a hydrogen atom, a halogeno group, a C1-6 haloalkoxy group, a carbamoyl group, a thiocarbamoyl group, or a cyano group.
  • An insecticide comprising at least one compound or a salt thereof according to [1] as an active ingredient.
  • the (hetero)aryl urea compound of the present invention has excellent insecticidal activity, is safe, and can be synthesized industrially advantageously.
  • the insecticide of the present invention can effectively control agricultural pests at low concentrations.
  • the first embodiment of the present invention is a compound represented by formula (I) (hereinafter, sometimes referred to as compound (I)) or a salt thereof. (Hereinafter, compound (I) or a salt thereof may be referred to as a (hetero)aryl urea compound.)
  • the term "unsubstituted” means that only the group serving as the mother nucleus is present. When the term “substituted” is not used and only the name of the group serving as the mother nucleus is used, it means “unsubstituted” unless otherwise specified.
  • the term “substituted” means that any hydrogen atom of the core group is replaced with a group (substituent) having the same or different structure as the core group. Therefore, a “substituent” is another group bonded to the core group.
  • the number of substituents may be one or more.
  • the two or more substituents may be the same or different.
  • C1-6 indicates that the number of carbon atoms in the core group is 1 to 6. This number of carbon atoms does not include the number of carbon atoms in the substituent.
  • a butyl group having an ethoxy group as a substituent is classified as a C2 alkoxy C4 alkyl group.
  • the "substituent” is not particularly limited as long as it is chemically permissible and has the effect of the present invention. Examples of groups that can be the “substituent” are shown below. C1-6 alkyl groups such as a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an s-butyl group, an i-butyl group, a t-butyl group, an n-pentyl group, or an n-hexyl group; C2-6 alkenyl groups such as a vinyl group, a 1-propenyl group, a 2-propenyl group (allyl group), a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a 1-methyl-2-propenyl group, and a 2-methyl-2-propenyl group; C2-6 alkynyl groups such as an ethyny
  • C3-6 cycloalkyl groups such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group; C6-10 aryl groups such as phenyl groups and naphthyl groups; C6-10 aryl C1-6 alkyl groups such as a benzyl group and a phenethyl group; 3- to 6-membered heterocyclyl groups; 3-6 membered heterocyclyl C1-6 alkyl group;
  • C1-6 alkoxy groups such as a methoxy group, an ethoxy group, an n-propoxy group, an i-propoxy group, an n-butoxy group, an s-butoxy group, an i-butoxy group, or a t-butoxy group
  • C2-6 alkenyloxy groups such as a vinyloxy group, an allyloxy group, a propenyloxy group, or a butenyloxy group
  • C2-6 alkynyloxy groups such as ethynyloxy groups, propargyloxy groups, etc.
  • C6-10 aryloxy groups such as a phenoxy group and a naphthoxy group
  • C6-10 aryl C1-6 alkoxy groups such as a benzyloxy group and a phenethyloxy group
  • 5- to 6-membered heteroaryloxy groups such as thiazolyloxy groups and pyridyloxy groups
  • Formyl group C1-6 alkylcarbonyl groups such as acetyl group and propionyl group; Formyloxy group; C1-6 alkylcarbonyloxy groups such as an acetyloxy group or a propionyloxy group; C6-10 arylcarbonyl groups such as a benzoyl group; C1-6 alkoxycarbonyl groups such as a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an i-propoxycarbonyl group, an n-butoxycarbonyl group, or a t-butoxycarbonyl group; C1-6 alkoxycarbonyloxy groups such as a methoxycarbonyloxy group, an ethoxycarbonyloxy group, an n-propoxycarbonyloxy group, an i-propoxycarbonyloxy group, an n-butoxycarbonyloxy group, or a t-butoxycarbonyloxy group; Carboxyl group;
  • halogeno groups such as a fluoro group, a chloro group, a bromo group, or an iodo group
  • C1-6 haloalkyl groups such as a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a 2,2,2-trifluoroethyl group, a pentafluoroethyl group, a 3,3,3-trifluoropropyl group, a 2,2,3,3,3-pentafluoropropyl group, a perfluoropropyl group, a 2,2,2-trifluoro-1-trifluoromethylethyl group, a perfluoroisopropyl group, a 4-fluorobutyl group, a 2,2,3,3,4,4,4-heptafluorobutyl group, a perfluorobutyl group, a perfluoropentyl group, a perfluorohexyl group, a chloromethyl group
  • Amino group C1-6 alkyl-substituted amino groups such as methylamino group, dimethylamino group, and diethylamino group; C6-10 arylamino groups such as anilino group and naphthylamino group; C6-10 aryl C1-6 alkylamino groups such as a benzylamino group or a phenethylamino group; Formylamino group; C1-6 alkylcarbonylamino groups such as an acetylamino group, a propanoylamino group, a butyrylamino group, or an i-propylcarbonylamino group; C1-6 alkoxycarbonylamino groups such as a methoxycarbonylamino group, an ethoxycarbonylamino group, an n-propoxycarbonylamino group, or an i-propoxycarbonylamino group; unsubstituted or substituted aminocarbonyl groups, such as an
  • C1-6 alkylthio groups such as a methylthio group, an ethylthio group, an n-propylthio group, an i-propylthio group, an n-butylthio group, an i-butylthio group, an s-butylthio group, or a t-butylthio group
  • C1-6 haloalkylthio groups such as a trifluoromethylthio group, a 2,2,2-trifluoroethylthio group, etc.
  • C6-10 arylthio groups such as a phenylthio group and a naphthylthio group
  • 5- to 6-membered heteroarylthio groups such as thiazolylthio groups and pyridylthio groups
  • C1-6 alkylthio groups such as a methylthio group, an ethylthio group, an n-propylthio group, an i-propy
  • C1-6 alkylsulfinyl groups such as a methylsulfinyl group, an ethylsulfinyl group, or a t-butylsulfinyl group; C1-6 haloalkylsulfinyl groups such as a trifluoromethylsulfinyl group or a 2,2,2-trifluoroethylsulfinyl group; C6-10 arylsulfinyl groups such as a phenylsulfinyl group; 5- to 6-membered heteroarylsulfinyl groups such as thiazolylsulfinyl groups and pyridylsulfinyl groups;
  • C1-6 alkylsulfonyl groups such as a methylsulfonyl group, an ethylsulfonyl group, or a t-butylsulfonyl group; C1-6 haloalkylsulfonyl groups such as a trifluoromethylsulfonyl group or a 2,2,2-trifluoroethylsulfonyl group; C6-10 arylsulfonyl groups such as a phenylsulfonyl group; 5- to 6-membered heteroarylsulfonyl groups such as thiazolylsulfonyl groups and pyridylsulfonyl groups; C1-6 alkylsulfonyloxy groups such as a methylsulfonyloxy group, an ethylsulfonyloxy group, or a t-butylsulfonyloxy group; C1-6 haloalkyls
  • triC1-6 alkyl-substituted silyl groups such as a trimethylsilyl group, a triethylsilyl group, or a t-butyldimethylsilyl group; triC6-10 aryl-substituted silyl groups such as triphenylsilyl groups; Cyano group; Nitro group.
  • any of the hydrogen atoms in these "substituents” may be replaced with a group of a different structure.
  • examples of the "substituents” include a C1-6 alkyl group, a C1-6 haloalkyl group, a C1-6 alkoxy group, a C1-6 haloalkoxy group, a halogeno group, a cyano group, and a nitro group.
  • the above “3- to 6-membered heterocyclyl group” contains 1 to 4 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur atoms as ring-constituting atoms.
  • Examples of the “3- to 6-membered heterocyclyl group” include 3- to 6-membered saturated heterocyclyl groups, 5- to 6-membered partially unsaturated heterocyclyl groups, and 5- to 6-membered heteroaryl groups.
  • Examples of the 3- to 6-membered saturated heterocyclyl group include an aziridinyl group, an epoxy group, a pyrrolidinyl group, a tetrahydrofuranyl group, a thiazolidinyl group, a piperidyl group, a piperazinyl group, a morpholinyl group, a dioxolanyl group, and a dioxanyl group.
  • Examples of the 5-membered partially unsaturated heterocyclyl group include a pyrrolinyl group, a dihydrofuranyl group, an imidazolinyl group, a pyrazolinyl group, an oxazolinyl group, and an isoxazolinyl group.
  • Examples of the six-membered partially unsaturated heterocyclyl group include a dihydropyranyl group.
  • Examples of the 5-membered heteroaryl group include a pyrrolyl group, a furyl group, a thienyl group, an imidazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an isothiazolyl group, a triazolyl group, an oxadiazolyl group, a thiadiazolyl group, and a tetrazolyl group.
  • 6-membered heteroaryl group examples include a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, and a triazinyl group.
  • a 1 represents a nitrogen atom or a group represented by CH.
  • R 1 represents a C1-6 haloalkoxy group or a C1-6 haloalkylthio group.
  • C1-6 haloalkoxy group include a difluoromethoxy group, a trifluoromethoxy group; a 2,2-difluoroethoxy group, a 2,2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, a pentafluoroethoxy group; a 3,3-difluoropropoxy group, a 3,3,3-trifluoropropoxy group, a 2,2,3,3,3-pentafluoropropoxy group, a 1,2,2,3,3,3-hexafluoropropoxy group, a perfluoropropoxy group; a 2,2,2-trifluoro-1-trifluoromethylethoxy group, a perfluoroisopropoxy group; a 2,2,3,3,4,4,4-heptafluoro
  • C1-6 haloalkylthio group includes difluoromethylthio group, trifluoromethylthio group, 2,2-difluoroethylthio group, 2,2,2-trifluoroethylthio group, 1,1,2,2-tetrafluoroethylthio group, pentafluoroethylthio group, 3,3-difluoropropylthio group, 3,3,3-trifluoropropylthio group, 2,2,3,3,3-pentafluoropropylthio group, 1,2,2,3,3,3-hexafluoropropylthio group, perfluoropropylthio group, 2,2,2-trifluoro-1-trifluoromethylethylthio group, perfluoroisopropylthio group, 2,2,3,3,4,4,4-heptafluorobutylthio group, 1,2,2,3,3,4,4,4-octafluoropropylthio group, Examples include
  • R1 is preferably a C1-2 fluoroalkoxy group such as a difluoromethoxy group, a trifluoromethoxy group, a 2,2-difluoroethoxy group, a 2,2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, or a pentafluoroethoxy group; or a C1-2 fluoroalkylthio group such as a difluoromethylthio group, a trifluoromethylthio group, a 2,2-difluoroethylthio group, a 2,2,2-trifluoroethylthio group, a 1,1,2,2-tetrafluoroethylthio group, or a pentafluoroethylthio group.
  • R 1 is preferably a 2,2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, or a trifluoromethylthio
  • R a represents a hydrogen atom, or a substituted or unsubstituted C3-6 cycloalkyl group.
  • C3-6 cycloalkyl group include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.
  • Preferred substituents on a "C3 to 6 cycloalkyl group” are: a halogeno group such as a fluoro group, a chloro group, a bromo group or an iodo group; a hydroxyl group; a C1 to 6 alkoxy group such as a methoxy group, an ethoxy group, an n-propoxy group, an i-propoxy group, an n-butoxy group, an s-butoxy group, an i-butoxy group or a t-butoxy group; a C1 to 6 haloalkoxy group such as a 2-chloro-n-propoxy group, a 2,3-dichlorobutoxy group or a trifluoromethoxy group; a phenyl group; a "phenyl group substituted with a halogeno group, a C1 to 6 haloalkyl group or a C1 to 6 haloalkoxy group” such as a 4-chlor
  • B 1 represents a nitrogen atom or a group represented by CH
  • B 2 represents a nitrogen atom or a group represented by CX b .
  • Xa and Xb each independently represent a hydrogen atom, a halogeno group, a C1-6 haloalkoxy group, a carbamoyl group, a thiocarbamoyl group, or a cyano group.
  • halogeno group include a fluoro group, a chloro group, a bromo group, and an iodo group.
  • C1-6 haloalkoxy group include the same groups as those exemplified for R1 .
  • the salt of compound (I) in this embodiment is not particularly limited as long as it is an agriculturally and horticulturally acceptable salt.
  • Examples of salts of compound (I) include salts of inorganic acids such as hydrochloric acid and sulfuric acid; salts of organic acids such as acetic acid and lactic acid; salts of alkali metals such as lithium, sodium, and potassium; salts of alkaline earth metals such as calcium and magnesium; salts of transition metals such as iron and copper; salts of ammonia; and salts of organic bases such as triethylamine, tributylamine, pyridine, and hydrazine.
  • the method for producing the compound (I) of the present embodiment is not particularly limited.
  • the compound (I) can be obtained by a production method utilizing a known reaction described in the Examples, etc.
  • it can be obtained by the production method described in Patent Document 1.
  • the salt of compound (I) can be obtained from compound (I) by a known method.
  • Compound (I) of the present embodiment can be obtained, for example, by utilizing a reaction as shown in the reaction scheme below.
  • Reaction Scheme 1 Compound (I) can be obtained by reacting a compound represented by formula (I-1) with a compound represented by formula (I-2). This reaction can be carried out in the presence of a base or a catalyst.
  • the second embodiment of the present invention is an insecticide containing at least one selected from the compound (I) of the first embodiment or a salt thereof as an active ingredient.
  • the amount of the (hetero)aryl urea compound contained in the insecticide of this embodiment is not particularly limited as long as it shows an insecticidal effect.
  • the (hetero)aryl urea compound of the present embodiment is a highly safe substance because it has little phytotoxicity to crops and low toxicity to fish and warm-blooded animals, and is therefore useful as an active ingredient of insecticides.
  • the (hetero)aryl urea compound of the present embodiment exhibits excellent control effects not only against susceptible pests, but also against various resistant pests.
  • the (hetero)aryl urea compound of the present embodiment (hereinafter, sometimes referred to as the compound of the present invention) is effective against all developmental stages of organisms to be controlled, and exhibits excellent control effects against, for example, eggs, nymphs, larvae, pupae, and adults of mites, insects, and the like.
  • the insecticide of the second embodiment is preferably used on plants such as grains, vegetables, root vegetables, potatoes, flowers, fruit trees, ornamental plants, trees such as tea, coffee, and cacao, pasture grasses, turf grasses, and cotton.
  • the insecticide may be applied to any part of the plant, such as leaves, stems, stalks, flowers, buds, fruits, seeds, sprouts, roots, tubers, tuberous roots, shoots, cuttings, etc.
  • the insecticide is not particularly limited by the species of the plant to which it is applied, and examples of the species of the plant include original species, varieties, improved varieties, cultivated varieties, mutants, hybrids, genetically modified organisms (GMOs), and the like.
  • the above insecticides can be used for controlling various agricultural pests by seed treatment, foliage spray, soil application, water surface application, and the like.
  • Butterflies or moths of the order Lepidoptera (a) Arctiidae moths, such as Hyphantria cunea and Lemyra imparilis; (b) Bucculatricidae moths, for example, Bucculatrix pyrivorella; (c) moths of the family Carposinidae, for example, the peach fruit moth (Carposina sasakii); (d) Crambidae moths, for example, Diaphania spp., Diaphania indica, Diaphania nitidalis; for example, Ostrinia spp., Ostrinia furnacalis, Ostrinia nubilalis, Ostrinia scapulalis; others, Chilo suppressalis, Cnaphalocrocis medinalis, Conogethes punct
  • Heliothis spp. for example, Heliothis armigera, Heliothis virescens; others, for example, Aedia leucomelas, Ctenoplusia agnata, Eudocima tyrannus, Mamestra brassicae, Mythimna separata, Naranga aenescens, Panolis japonica, Peridroma saucia, Pseudoplusia includens, Trichoplusia ni); (m) Nolidae moths, for example, Earias insulana; (n) Butterflies of the family Pieridae, for example, Pieris spp., Pieris brassicae, Pieris rapae crucivora; (O) Plutellidae moths, for example, Acrolepiopsis spp., such as Acrolepiopsis sapporensis and Acrolepiopsis suzukiella; others, such as Plutella x
  • Thysanoptera pests (a) Phlaeothripidae, for example, Ponticulothrips diospyrosi; (b) Thripidae, for example, Frankliniella spp., Frankliniella intonsa, Frankliniella occidentalis; Thrips spp., Thrips palmi, Thrips tabaci; and others, Heliothrips haemorrhoidalis, Scirtothrips dorsalis.
  • Phlaeothripidae for example, Ponticulothrips diospyrosi
  • Thripidae for example, Frankliniella spp., Frankliniella intonsa, Frankliniella occidentalis
  • Thrips spp. Thrips palmi, Thrips tabaci
  • Heliothrips haemorrhoidalis Scirtothrips dorsalis.
  • Cicadellidae for example, Empoasca spp., potato leafhopper (Empoasca fabae), persimmon leafhopper (Empoasca nipponica), tea green leafhopper (Empoasca onukii), bean green leafhopper (Empoasca sakaii); other, Arboridia apicalis, Balclutha saltuella, Epiacanthus stramineus, Macrosteles striifrons, Nephotettix cinctinceps.
  • Empoasca spp. potato leafhopper (Empoasca fabae), persimmon leafhopper (Empoasca nipponica), tea green leafhopper (Empoasca onukii), bean green leafhopper (Empoasca sakaii); other, Arboridia apicalis, Balclutha saltuella, Epiacanthus stramineus, Macrosteles striifrons, Nephotettix cinctinceps.
  • C Heteroptera
  • Alydidae for example, Riptortus clavatus
  • Coreidae for example, Cletus punctiger, Leptocorisa chinensis
  • Lygaeidae for example, Blissus leucopterus, Cavelerius saccharivorus, Togo hemipterus
  • Miridae for example, Halticus insularis, Lygus lineolaris, Psuedatomoscelis seriatus, Stenodema sibiricum, Stenotus rubrovittatus, Trigonotylus caelestialium
  • Miridae for example, Halticus insularis, Lygus lineolaris, Psuedatomoscelis seriatus, Stenodema sibiricum, Stenotus rubrovittatus, Trigonotylus caelestialium
  • Pentatomidae for example, Nezara spp., Nezara antennata, Nezara viridula; for example, Eysarcoris spp., Eysarcoris aeneus, Eysarcoris lewisi, Eysarcoris ventralis, Dolycoris baccarum, Eurydema rugosum, Glaucias subpunctatus, Halyomorpha halys, Piezodorus hybneri), Plautia crossota, Scotinophora lurida;
  • Pyrrhocoridae for example, Dysdercus cingulatus;
  • Rhopalidae for example, Rhopalus msculatus;
  • Scutelleridae for example, Eurygaster integriceps;
  • Tingidae for example, Stephanitis nashi.
  • (D) Sternorrhyncha (a) Adelgidae, for example, Adelges laricis; (b) Aleyrodidae, for example, Bemisia spp., silverleaf whitefly (Bemisia argentifolii), tobacco whitefly (Bemisia tabaci); other, Aleurocanthus spiniferus, Dialeurodes citri, Trialeurodes vaporariorum; (c) Aphididae, for example, Aphis spp., bean aphid (Aphis craccivora), bean black aphid (Aphis fabae), strawberry aphid (Aphis forbesi), cotton aphid (Aphis gossypii), European apple aphid (Aphis pomi), elder aphid (Aphis sambuci), Yukiyanagi aphid (Aphis spiraecola); for example, Rhopalosiphum s
  • Pests of the suborder Polyphaga (a) of the family Anobiidae, for example, the cigarette beetle (Lasioderma serricorne); (b) Attelabidae, for example, Byctiscus betulae, Rhynchites heros; (C) Bostrichidae, for example, Lyctus brunneus; (d) Brentidae, for example, Cylas formicarius; (e) Buprestidae, for example, Agrilus sinuatus; (F) Cerambycidae, for example, Anoplophora malasiaca, Monochamus alternatus, Psacothea hilaris, Xylotrechus pyrrhoderus; (g) Chrysomelidae, for example, Bruchus spp., pea weevil (Bruchus pisorum), broad bean weevil (Bruchus rufimanus); for example, Diabrotica spp., northern
  • Curculionidae for example, Anthonomus spp., such as Anthonomus grandis and Anthonomus pomor
  • Pests of the order Diptera (A) Suborder Brachycera (a) Agromyzidae, for example, Liriomyza spp., Liriomyza bryoniae, Liriomyza chinensis, Liriomyza sativae, Liriomyza trifolii; others, Chromatomyia horticola, Agromyza oryzae; (b) Anthomyiidae, for example, Delia spp., such as Delia platura and Delia radicum; and others, such as Pegomya cunicularia; (C) Drosophilidae, for example, Drosophila spp., Drosophila melanogaster, Drosophila suzukii; (D) Ephydridae, for example, Hydrellia griseola; (e) from the family Psilidae, for example, the carrot fly (Psila rosae); (F) Teph
  • Nematocera (A) Cecidomyiidae, for example, Asphondylia yushimai, Contarinia sorghicola, Mayetiola destructor, and Sitodiplosis mosellana.
  • Orthoptera pests for example, Schistocerca spp., American locust (Schistocerca americana), desert locust (Schistocerca gregaria); other, Australian locust (Chortoicetes terminifera),ixie locust (Dociostaurus maroccanus), migratory locust (Locusta migratoria), brown locust (Locustana pardalina), red locust (Nomadacris septemfasciata), Oxya yezoensis; (b) from the family Gryllidae, for example, the European house cricket (Acheta domestica), the field cricket (Teleogryllus emma); (c) Gryllotalpidae, for example, Gryllotalpa orientalis; (d) From the family Tettigoniidae, for example, Tachycines asynamorus.
  • Acrididae for example, Schistocerca spp., American locust
  • the insecticide of the second embodiment of the present invention may be mixed or used in combination with other active ingredients such as fungicides, insecticides/acaricides, nematicides, and soil pesticides; plant regulators, synergists, fertilizers, soil conditioners, and animal feed.
  • active ingredients such as fungicides, insecticides/acaricides, nematicides, and soil pesticides; plant regulators, synergists, fertilizers, soil conditioners, and animal feed.
  • the combination of the compound of the present invention and other active ingredients is expected to have a synergistic effect in terms of insecticidal, acaricidal and nematocidal activities.
  • the synergistic effect can be confirmed by Colby's formula (Colby.SR; Calculating Synergistic and Antagonistic Responses of Herbicide Combinations; Weeds 15, 20-22, 1967) in accordance with a conventional method.
  • insecticides examples include acaricides, nematicides, soil pesticides, etc. that can be mixed or used in combination with the insecticide of the present invention are shown below. The following list is based on the IRAC insecticide mode of action classification table.
  • Acetylcholinesterase (AChE) inhibitors (carbamate type) Alanycarb, Aldicarb, Bendiocarb, Benfuracarb, Butocarboxim, Butoxycarboxim, Carbaryl, Carbofuran, Carbosulfan, Ethiofencarb, Fenobucarb, Formetanate, Furathiocarb, Isoprocarb, Methiocarb, Methomyl, Metolcarb, Oxamyl, Piricarb micarb, Propoxur, Thiodicarb, Thiofanox, Triazamate, Trimethacarb, XMC, Xylylcarb; Aldoxycarb, Allyxycarb, Aminocarb, Bufencarb, Cloethocarb, Fenothiocarb, Promecarb.
  • AChE Acetylcholinesterase
  • Acetylcholinesterase (AChE) inhibitors organophosphorus (organophosphorus) Acephate, Azamethiphos, Azinphos-ethyl, Azinphosmethyl, Cadusafos, Chlorethoxyfos, Chlorfenvinphos, Chlormephos, Chlorpyrifos, Chlorpyrifos-methyl, Coumaphos, Cyanophos, Demeton-S-methyl, Diazinon, Dichlorvos DDVP), Dicrotophos, Dimethoate, Dimethylvinphos, Disulfoton, EPN, Ethion, Ethoprophos, Famphur, Fenamiphos, Fenitrothion, Fenthion, Fosthiazate, Heptenophos, Imicyafos, Isofenphos, Isopropyl O-(methoxyaminothio-phosphoryl) salicylate salicylate, Isoxathion, Malathion, Mecarb
  • chloride ion channel blockers Chlordane, Endosulfan; Ethiprole, Fipronil; Acetoprole, Camphechlor, Dienochlor, Heptachlor, Pyrafluprole, Pyriprole; Flufiprole.
  • Nicotinic acetylcholine receptor (nAChR) competitive modulators Acetamiprid, Clothianidin, Dinotefuran, Imidacloprid, Nitenpyram, Thiacloprid, Thiamethoxam; Nicotine; Sulfoxaflor; Flupyradifurone; Triflumezopyrim; Nithiazine, Dichloromezotiaz, Flupyrimin.
  • Glutamate-gated chloride ion (chloride ion) channel (GluCl) allosteric modulators Abamectin, Emamectin, Emamectin-benzoate, Lepimectin, Milbemectin; Doramectin, Eprinomectin, Ivermectin, Moxidectin, Selamectin.
  • Chitin biosynthesis inhibitor type 0 Bistrifluron, Chlorfluazuron, Diflubenzuron, Flucycloxuron, Flufenoxuron, Hexaflumuron, Lufenuron, Novaluron, Noviflumuron, Teflubenzuron, Triflumuron; Fluazuron.
  • Chitin biosynthesis inhibitor type 1 Buprofezin.
  • Molting inhibitor Cyromazine.
  • Mitochondrial electron transport chain complex IV inhibitors Aluminum phosphide (Al-phosphide), calcium phosphide (Ca-phosphide), zinc phosphide (Zn-phosphide), phosphine (Phosphine); calcium cyanide (Ca-cyanide), sodium cyanide (Na-cyanide), potassium cyanide (K-cyanide).
  • mitochondrial electron transport chain complex II inhibitors Cyenopyrafen, Cyflumetofen; Pyflubumide.
  • Baculovirus granulosis viruses (Cydia pomonella GV, Thaumatotibia leucotreta GV) Nuclear polyhedrosis viruses (Anticarsia gemmatalis MNPV, Heliocoverpa armigera NPV).
  • KCa2 Calcium-activated potassium channel
  • 32) Mitochondrial electron transport complex III inhibitor (Qi site) Flometoquin.
  • Chordotonal organ modulator (target site unspecified) Dimpropyridaz.
  • anthelmintics that can be mixed or used in combination with the insecticide of the present invention are shown below.
  • Benzimidazoles fenbendazole, albendazole, triclabendazole, oxibendazole, mebendazole, oxfendazole, perbendazole, flubendazole, febantel, netobimin, thiophanate, thiabendazole, and cambendazole.
  • Salicylanilides closantel, oxyclozanide, rafoxanide, niclosamide.
  • Substituted phenols nitroxynil, nitrosulfonate.
  • Pyrimidines pyrantel, morantel.
  • Imidazothiazoles levamisole, tetramisole.
  • Tetrahydropyrimidines praziquantel, epsiprantel.
  • Other anthelmintics cyclodiene, ryania, clorsulon, metronidazole, demiditraz, piperazine, diethylcarbamazine, dichlorophene, monepantel, tribendimidine, amidantel, thiacetarsamide, melarsomine, and arsenamide.
  • Nucleic acid synthesis metabolic inhibitors (1) RNA polymerase I inhibitors Benalaxyl, Benalaxyl M, Furalaxyl, Metalaxyl, Metalaxyl M; Oxadixyl; Ofurace. (2) Adenosine deaminase inhibitors: bupirimate, dimethirimol, ethirimol. (3) DNA/RNA biosynthesis inhibitors: hymexazole, octhilinone. (4) DNA topoisomerase type II inhibitor oxolinic acid. (5) DHODH inhibitors: ipflufenoquine, quinofumelin.
  • Inhibitors of cytoskeleton and motor proteins (1) ⁇ -tubulin polymerization inhibitors: benomyl, carbendazim, fuberidazole, thiabendazole, thiophanate, thiophanate-methyl, diethofencarb, zoxamide, ethaboxam. (2) Other inhibitors: Pencycuron, fluopicolide, fenamacryl, metrafenone, pyriophenone, pyridaclomethyl.
  • Inhibitors of sterol biosynthesis in cell membranes (1) Inhibitors of C14 demethylase (erg11/cyp51) in sterol biosynthesis Triforine; pyrifenox, pyrisoxazole; fenarimol, nuarimol; imazalil, oxpoconazole, pefurazoate, prochloraz, triflumizole; azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, mefentrifluconazole, metconazole, myclobutanil, penconazole, propiconazole, simeconazole, tebuconazole
  • Inhibitors of cell wall melanin synthesis Fthalide; pyroquilon; tricyclazole. Carpropamid, diclocymet, fenoxanil. Tolprocarb.
  • (L) Agents exhibiting multisite contact activity Copper (various salts), basic copper sulfate, Bordeaux mixture, copper hydroxide, copper naphthalate, copper oxychloride, copper sulfate, copper oxide, copper oxine; sulfur, lime sulfur mixture; ferbam, mancozeb, maneb, metiram, propineb, thiuram, zinc thiazole, zineb, ziram; captan, captafol, folpet; chlorothalonil; dichlofluanid, tolylfluanid; guazatine, guazatine acetate, iminoctadine, iminoctadine acetate, iminoctadine albesilate; anilazine; dithianone; quinomethionate; fluoroimide; metasulfocarb.
  • plant regulators that can be mixed or used in combination with the insecticide of the present invention are shown below.
  • Formulation The formulations of the insecticide of the present invention are shown below, but the additives and the ratio of addition should not be limited to these examples and can be changed in a wide range. In the formulations, parts indicate parts by mass, and % indicates % by mass. The formulations for agricultural and horticultural use and for paddy rice are shown below.
  • Formulation 4 Granules 5 parts of the compound of the present invention, 73 parts of clay, 20 parts of bentonite, 1 part of dioctyl sulfosuccinate sodium salt, and 1 part of potassium phosphate are thoroughly ground and mixed, water is added, the mixture is thoroughly kneaded, and then granulated and dried to obtain granules containing 5% of the active ingredient.
  • Formulation 5 Suspension 10 parts of the compound of the present invention, 4 parts of polyoxyethylene alkyl allyl ether, 2 parts of sodium polycarboxylate, 10 parts of glycerin, 0.2 parts of xanthan gum, and 73.8 parts of water are mixed and wet-pulverized until the particle size becomes 3 microns or less, to obtain a suspension containing 10% of the active ingredient.
  • TEA triethylamine.
  • DMF N,N-dimethylformamide.
  • THF tetrahydrofuran.
  • DIPEA diisopropylethylamine.
  • DMAP 4-dimethylaminopyridine.
  • TMEDA tetramethylethylenediamine.
  • Boc2O di-tert-butyl dicarbonate.
  • tBuXPhos 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl.
  • Pd2(dba)3 tris(dibenzylideneacetone)dipalladium(0).
  • Pd(PPh3)4 tetrakis(triphenylphosphine)palladium(0).
  • tert-butyl [1-[ ⁇ (dimethylamino)methylene ⁇ amino]-1-oxopropan-2-yl]carbamate (12.9 g) was dissolved in 1,4-dioxane (180 ml) and acetic acid (89 ml), and 2-hydrazineylpyrimidine (7.0 g) was added thereto and stirred at 60° C. for 4 hours. The reaction mixture was then evaporated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (11.0 g) in a yield of 71%.
  • Trifluoroethanol (0.6 g) was dissolved in DMF (4 ml) and cooled to 0° C. Sodium hydride (0.24 g) was then added and the mixture was stirred at 0° C. for 30 minutes. Thereafter, 2-fluoro-1-nitro-4-(trifluoromethyl)benzene (0.84 g) was added and the mixture was further stirred at room temperature overnight. Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (1.23 g).
  • 2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)aniline (0.22 g) was dissolved in THF (4 ml) and cooled to 0° C. Then, TEA (0.36 ml) and triphosgene (0.1 g) were added in that order and stirred at 0° C. for 30 minutes. Then, 1- ⁇ 1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl ⁇ ethan-1-aminedihydrochloride (0.22 g) and TEA (0.36 ml) were added and the mixture was further stirred at room temperature for 2 hours.
  • 6-(trifluoromethyl)pyridin-3-amine (17.6 g) was dissolved in dichloromethane (270 ml), and DIPEA (22.8 ml), DMAP (1.33 g), and pivaloyl chloride (14.7 ml) were added successively, and the mixture was stirred at room temperature overnight.
  • the reaction mixture was then mixed with a saturated aqueous solution of sodium bicarbonate, extracted with dichloromethane, washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate.
  • the solvent was then distilled off under reduced pressure, and the resulting crystals were washed with diethyl ether to obtain the target compound (13.93 g). Yield: 52%.
  • N-(6-(trifluoromethyl)pyridin-3-yl)pivalamide (4.26 g) was dissolved in THF (58 ml), TMEDA (6.4 ml) was added, and the mixture was cooled to ⁇ 78° C. Then, a 2.64 M nBuLi hexane solution (16 ml) was added dropwise, and the mixture was further stirred at ⁇ 78° C. for 1 hour. Thereafter, a solution of iodine (5.3 g) in THF (35 ml) was added, the temperature was raised to 0° C., and the mixture was further stirred for 1 hour.
  • N-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)pivalamide (0.59 g) was dissolved in concentrated sulfuric acid (5.6 ml) and stirred at 100° C. for 1 hour. The reaction mixture was then added to a saturated aqueous solution of sodium carbonate, extracted with ethyl acetate, washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure to obtain the target compound (0.44 g). Yield: 100%.
  • 6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine (0.1 g) was dissolved in THF (1.9 ml) and cooled to 0° C. Then, TEA (0.16 ml) and triphosgene (45 mg) were added in that order and stirred at 0° C. for 30 minutes. Then, 1- ⁇ 1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl ⁇ ethan-1-amine dihydrochloride (0.11 g) and TEA (0.16 ml) were added and the mixture was further stirred at room temperature for 4 hours.
  • 6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine 80 mg was dissolved in THF (1.6 ml) and cooled to 0° C. Then, TEA (0.13 ml) and triphosgene (36 mg) were added in that order and stirred at 0° C. for 30 minutes. Then, 1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine (75 mg) and TEA (0.13 ml) were added and the mixture was further stirred at room temperature for 2 hours.
  • tert-butyl [1-[ ⁇ (dimethylamino)methylene ⁇ amino]-1-oxopropan-2-yl]carbamate (2.3 g) was dissolved in 1,4-dioxane (31 ml) and acetic acid (16 ml), and 5-fluoro-2-hydrazineylpyridine (1.45 g) was added thereto and stirred at 60° C. for 4 hours. The reaction mixture was then evaporated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (1.9 g) in a yield of 66%.
  • tert-butyl (1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate (1.9 g) was dissolved in dichloromethane (40 ml), and a 4M solution of hydrochloric acid in 1,4-dioxane (8 ml) was added thereto, followed by stirring at room temperature overnight. The reaction mixture was then evaporated under reduced pressure to give crystals which were then used in the next step.
  • 6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine (0.1 g) was dissolved in THF (1.9 ml) and cooled to 0° C. Then, TEA (0.16 ml) and triphosgene (45 mg) were added in that order and stirred at 0° C. for 30 minutes. Then, 1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine hydrochloride (93 mg) and TEA (0.16 ml) were added and the mixture was further stirred at room temperature for 4 hours.
  • tert-butyl [1-[ ⁇ (dimethylamino)methylene ⁇ amino]-1-oxopropan-2-yl]carbamate (18.5 g) was dissolved in 1,4-dioxane (250 ml) and acetic acid (130 ml), and 6-hydrazineylnicotinonitrile (12.2 g) was added thereto, followed by stirring at 60° C. for 4 hours. The reaction mixture was then evaporated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (4.52 g) in a yield of 19%.
  • tert-butyl (1-(1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl) ethyl) carbamate (1.93 g) was dissolved in dichloromethane (41 ml), and a 4M solution of hydrochloric acid in 1,4-dioxane (8 ml) was added thereto, followed by stirring at room temperature overnight. The reaction mixture was then evaporated under reduced pressure to give crystals which were then used in the next step.
  • 6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine (0.1 g) was dissolved in THF (1.9 ml) and cooled to 0° C. Then, TEA (0.16 ml) and triphosgene (45 mg) were added in that order and stirred at 0° C. for 30 minutes. Thereafter, 6-(5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl)nicotinonitrile hydrochloride (96 mg) and TEA (0.16 ml) were added and the mixture was further stirred at room temperature for 4 hours.
  • 2-(1,3-dioxoisoindolin-2-yl)propanoic acid (5.4 g) was dissolved in dichloromethane (82 ml) and cooled to 0° C. Then, oxalyl chloride (4.2 ml) and a catalytic amount of DMF were added and stirred at room temperature for 1 hour. The solvent was then distilled off under reduced pressure to obtain the acid chloride. Next, ethyl cyclopropanecarbimidate hydrochloride (3.69 g) was dissolved in THF (82 ml) and cooled to 0°C. Then, DIPEA (17.2 ml) and the acid chloride were successively added, and the mixture was stirred at 0° C.
  • 6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine (0.11 g) was dissolved in THF (2.1 ml) and cooled to 0° C. Then, TEA (0.18 ml), triphosgene (0.12 g), and a catalytic amount of DMAP were added, and the mixture was stirred at room temperature for 1 hour.
  • reaction liquid was then evaporated under reduced pressure, and the residue was suspended in THF (2.1 ml), 1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine (0.13 g) and TEA (0.12 ml) were added, and the mixture was stirred at room temperature for 5 hours.
  • Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate.
  • the solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.15 g).
  • 6-(trifluoromethyl)pyridin-3-amine (10.0 g) was dissolved in dichloromethane (150 ml), TEA (10.3 ml) and DMAP (0.75 g) were added, and the mixture was cooled to 0° C. Then, BocO (14.9 ml) was added, and the mixture was stirred at room temperature overnight. Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (9.4 g). Yield: 58%.
  • tert-butyl (6-(trifluoromethyl)pyridin-3-yl)carbamate (10.86 g) was dissolved in THF (140 ml), TMEDA (15.4 ml) was added, and the mixture was cooled to ⁇ 78° C. Then, a 2.64 M nBuLi hexane solution (39 ml) was added dropwise, and the mixture was further stirred at ⁇ 78° C. for 1 hour. Then, 1,2-dibromoethane (8.8 ml) was added, the temperature was raised to room temperature, and the mixture was further stirred for 5 hours.
  • tert-butyl (4-bromo-6-(trifluoromethyl)pyridin-3-yl)carbamate (8.18 g) was dissolved in 120 ml of toluene, and trifluoroethanol (12.0 g), cesium carbonate (15.6 g), tBuXPhos (0.61 g), and Pd2(dba)3 (0.66 g) were added in that order, and the mixture was stirred at 80°C for 6 hours. Water was then added to the reaction mixture, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate.
  • tert-butyl (1-(1-(6-chloropyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate (0.65 g) was dissolved in DMF (8.0 ml), and zinc cyanide (0.71 g) and Pd( PPh3 ) 4 (0.23 g) were added successively and stirred at 80°C for 6 hours under a nitrogen atmosphere. Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate.
  • Step 2 Synthesis of 1-(1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea
  • tert-butyl (1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate (0.41 g) was dissolved in dichloromethane (10 ml) and cooled to 0° C. Then, trifluoroacetic acid (1.5 g) was added and the mixture was stirred at room temperature for 4 hours. The reaction mixture was then evaporated under reduced pressure to give 6-(5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl)pyrimidine-4-carbonitrile.
  • tert-butyl (1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl) carbamate (0.64 g) was dissolved in dichloromethane (12 ml), and 4M hydrochloric acid in 1,4-dioxane (2.2 ml) was added thereto, followed by stirring at room temperature overnight. The reaction mixture was then evaporated under reduced pressure to give crystals which were then used in the next step.
  • LCMS retention times were determined in the following manner.
  • a Waters CORTECS UPLC C18 column (Waters, 2.1 x 50 mm, 1.6 ⁇ m) was attached to a system consisting of an ultra-high performance, high-resolution liquid chromatograph (ACQUITY UPLC H-Class: manufactured by Waters), an ACQUITY UPLC photodiode array (PDA) e ⁇ detector (manufactured by Waters), and an ACQUITY QDa detector (positive and negative ion electrospray mode, UV PDA detection, manufactured by Waters), and measurements were performed at a temperature of 40°C, a flow rate of 0.6 mL/min, and 2 ⁇ L injection.
  • ACQUITY UPLC H-Class manufactured by Waters
  • PDA photodiode array
  • QDa detector positive and negative ion electrospray mode, UV PDA detection, manufactured by Waters
  • the concentration of the mobile phase (B) was maintained at 30% by mass for 0.15 minutes, then the concentration of the mobile phase (B) was increased from 30% by mass to 95% by mass at a constant rate over 1.35 minutes, maintained at 95% by mass for 0.5 minutes, then the concentration of the mobile phase (B) was immediately decreased to 30% by mass, and finally the concentration of the mobile phase (B) was maintained at 30% by mass for 0.50 minutes.
  • Table 1 shows a group of compounds prepared by the same method, including the compounds listed in the synthesis examples. Table 1 also lists the melting points as physical properties of the compounds.
  • Test Example 1 Efficacy test against armyworm Emulsion (I) was diluted with water to a set concentration to obtain a dilution (I). Emulsion (II) was diluted with water to a set concentration to obtain a dilution (II). Corn leaf pieces were immersed in dilution (I) and dilution (II) for 30 seconds. The immersion-treated corn leaf pieces were placed in a petri dish, and five second-instar armyworm larvae were released into the dish. The petri dish was left in a thermostatic chamber at a temperature of 25°C and a humidity of 60%. Six days after the release of the insects, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate. The results of the test are shown in Table 2 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
  • Emulsion (I) was diluted with water to a set concentration to obtain a dilution (I).
  • Emulsion (II) was diluted with water to a set concentration to obtain a dilution (II).
  • Cabbage leaves were immersed in each of dilution (I) and dilution (II) for 30 seconds. After the immersion treatment, the cabbage leaves were air-dried and placed in a petri dish, into which five second-instar larvae of Spodoptera litura were released. The petri dish was left in a thermostatic chamber at a temperature of 25°C and a humidity of 60%. Six days after the release of the insects, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate. The results of the test are shown in Table 3 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
  • Emulsion (I) was diluted with water to a set concentration to obtain dilution (I).
  • Emulsion (II) was diluted with water to a set concentration to obtain dilution (II).
  • Dilution (I) and dilution (II) were sprayed on bok choy seedlings (at the seventh true leaf development stage) planted in 3-inch pots.
  • the bok choy seedlings were air-dried and then placed in plastic cups.
  • Ten adult Striata stripes flea beetles were released into the cups and stored in a thermostatic chamber at a temperature of 25°C and a humidity of 65%. Seven days after the release of the insects, the survival rate was determined and the mortality rate was calculated.
  • the test was carried out in duplicate. The results of the test are shown in Table 9 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
  • Emulsion (I) was diluted with water to a set concentration to obtain dilution (I).
  • Emulsion (II) was diluted with water to a set concentration to obtain dilution (II).
  • Dilution (I) and dilution (II) were sprayed onto green bean leaf disks and air-dried. Seven days after spraying, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate. The results of the test are shown in Table 11 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
  • Control rate (%) ⁇ (Mc)-(Mt)/(Mc) ⁇ x 100
  • Mc Number of mines with a total length of 1 cm or more in the untreated area
  • Mt Number of mines with a total length of 1 cm or more in the spray-treated area
  • the (hetero)aryl urea compound of the present invention has excellent insecticidal activity, is safe, and can be synthesized industrially advantageously.
  • the insecticide of the present invention can effectively control agricultural pests at low concentrations.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Environmental Sciences (AREA)
  • Plant Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dentistry (AREA)
  • Agronomy & Crop Science (AREA)
  • Insects & Arthropods (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

A compound represented by formula (I) or a salt thereof. In formula (I): A1 is a nitrogen atom or a group represented by CH; R1 is a C1-6 haloalkoxy group or a C1-6 haloalkylthio group; Ra is a hydrogen atom or a substituted or unsubstituted C3-6 cycloalkyl group; B1 is a nitrogen atom or a group represented by CH; B2 is a nitrogen atom or a group represented by CXb; and Xa and Xb are independently a hydrogen atom, a C1-6 haloalkoxy group, a halogeno group, a carbamoyl group, a thiocarbamoyl group or a cyano group.

Description

（ヘテロ）アリールウレア化合物および殺虫剤(Hetero)aryl urea compounds and insecticides
　本発明は、（ヘテロ）アリールウレア化合物および殺虫剤に関する。より詳細に、本発明は、優れた殺虫活性を有し、安全性に優れ、かつ工業的に有利に合成できる（ヘテロ）アリールウレア化合物ならびにこれを有効成分として含有する殺虫剤に関する。
　本願は、２０２２年１１月１０日に、日本に出願された特願２０２２－１８０２５５号に基づき優先権を主張し、その内容をここに援用する。 The present invention relates to a (hetero)aryl urea compound and an insecticide. More specifically, the present invention relates to a (hetero)aryl urea compound that has excellent insecticidal activity, is safe, and can be synthesized industrially advantageously, and to an insecticide containing the same as an active ingredient.
This application claims priority based on Japanese Patent Application No. 2022-180255, filed on November 10, 2022, the contents of which are incorporated herein by reference.
　殺虫活性を有する化合物が種々提案されている。そのような化合物を農薬として実用するためには、効力が十分に高いだけでなく、薬剤抵抗性が生じ難いこと、植物に対する薬害や土壌汚染を生じさせないこと、家畜や魚類などに対する毒性が低いことなどが要求される。 Various compounds with insecticidal activity have been proposed. For such compounds to be useful as pesticides, they must not only be sufficiently effective, but also unlikely to develop drug resistance, not cause plant damage or soil contamination, and have low toxicity to livestock and fish.
　ところで、特許文献１は、式（P1）で表される化合物が、殺虫剤として使用可能であることを教示している。 Incidentally, Patent Document 1 teaches that the compound represented by formula (P1) can be used as an insecticide.
Figure JPOXMLDOC01-appb-C000002
Figure JPOXMLDOC01-appb-C000002
国際公開第２０２２／１５７１８８号International Publication No. 2022/157188
　本発明の課題は、殺虫活性に優れ、安全性に優れ且つ工業的に有利に合成できる（ヘテロ）アリールウレア化合物およびこれを有効成分として含有する殺虫剤を提供することである。 The object of the present invention is to provide a (hetero)aryl urea compound that has excellent insecticidal activity, is safe, and can be synthesized industrially in an advantageous manner, and an insecticide that contains the compound as an active ingredient.
〔１〕式（Ｉ）で表される化合物またはその塩。 [1] A compound represented by formula (I) or a salt thereof.
Figure JPOXMLDOC01-appb-C000003
Figure JPOXMLDOC01-appb-C000003
　式（Ｉ）中、
　Ａ１は、窒素原子、またはＣＨで表される基を示し、
　Ｒ１は、Ｃ１～６ハロアルコキシ基、またはＣ１～６ハロアルキルチオ基を示し、
　Ｒaは、水素原子、または置換若しくは無置換のＣ３～６シクロアルキル基を示し、
　Ｂ１は、窒素原子、またはＣＨで表される基を示し、
　Ｂ２は、窒素原子、またはＣＸｂで表される基を示し、
　ＸａおよびＸｂは、それぞれ独立に、水素原子、ハロゲノ基、Ｃ１～６ハロアルコキシ基、カルバモイル基、チオカルバモイル基、またはシアノ基を示す。
　〔２〕前記〔１〕に記載の化合物またはその塩からなる群から選ばれる少なくとも１つを有効成分として含有する殺虫剤。 In formula (I),
A 1 represents a nitrogen atom or a group represented by CH;
R 1 represents a C1-6 haloalkoxy group or a C1-6 haloalkylthio group;
R a represents a hydrogen atom or a substituted or unsubstituted C3-6 cycloalkyl group;
B1 represents a nitrogen atom or a group represented by CH;
B2 represents a nitrogen atom or a group represented by CXb ;
Xa and Xb each independently represent a hydrogen atom, a halogeno group, a C1-6 haloalkoxy group, a carbamoyl group, a thiocarbamoyl group, or a cyano group.
[2] An insecticide comprising at least one compound or a salt thereof according to [1] as an active ingredient.
　本発明の（ヘテロ）アリールウレア化合物は、殺虫活性に優れ、安全性に優れ且つ工業的に有利に合成できる。
　本発明の殺虫剤は、農業害虫を、低濃度で効果的に防除することができる。 The (hetero)aryl urea compound of the present invention has excellent insecticidal activity, is safe, and can be synthesized industrially advantageously.
The insecticide of the present invention can effectively control agricultural pests at low concentrations.
〔式（Ｉ）で表される化合物〕
　本発明の第１の実施形態は、式（Ｉ）で表される化合物（以下、化合物（Ｉ）ということがある。）またはその塩である。（以下、化合物（I）またはその塩を、（ヘテロ）アリールウレア化合物ということがある。） [Compound represented by formula (I)]
The first embodiment of the present invention is a compound represented by formula (I) (hereinafter, sometimes referred to as compound (I)) or a salt thereof. (Hereinafter, compound (I) or a salt thereof may be referred to as a (hetero)aryl urea compound.)
Figure JPOXMLDOC01-appb-C000004
Figure JPOXMLDOC01-appb-C000004
　本発明において、「無置換（unsubstituted）」の用語は、母核となる基のみであることを意味する。「置換」との記載がなく母核となる基の名称のみで記載しているときは、別段の断りがない限り「無置換」の意味である。
　一方、「置換（substituted）」の用語は、母核となる基のいずれかの水素原子が、母核と同一または異なる構造の基（置換基）で置換されていることを意味する。従って、「置換基」は、母核となる基に結合した他の基である。置換基は１つであってもよいし、２つ以上であってもよい。２つ以上の置換基は同一であってもよいし、異なっていてもよい。
　「Ｃ１～６」などの用語は、母核となる基の炭素原子数が１～６個などであることを表している。この炭素原子数には、置換基の中に在る炭素原子の数を含まない。例えば、置換基としてエトキシ基を有するブチル基は、Ｃ２アルコキシＣ４アルキル基に分類する。 In the present invention, the term "unsubstituted" means that only the group serving as the mother nucleus is present. When the term "substituted" is not used and only the name of the group serving as the mother nucleus is used, it means "unsubstituted" unless otherwise specified.
On the other hand, the term "substituted" means that any hydrogen atom of the core group is replaced with a group (substituent) having the same or different structure as the core group. Therefore, a "substituent" is another group bonded to the core group. The number of substituents may be one or more. The two or more substituents may be the same or different.
A term such as "C1-6" indicates that the number of carbon atoms in the core group is 1 to 6. This number of carbon atoms does not include the number of carbon atoms in the substituent. For example, a butyl group having an ethoxy group as a substituent is classified as a C2 alkoxy C4 alkyl group.
　「置換基」は化学的に許容され、本発明の効果を有する限りにおいて特に制限されない。以下に「置換基」となり得る基を例示する。
　メチル基、エチル基、ｎ－プロピル基、ｉ－プロピル基、ｎ－ブチル基、ｓ－ブチル基、ｉ－ブチル基、ｔ－ブチル基、ｎ－ペンチル基、ｎ－ヘキシル基などのＣ１～６アルキル基；
　ビニル基、１－プロペニル基、２－プロペニル基（アリル基）、１－ブテニル基、２－ブテニル基、３－ブテニル基、１－メチル－２－プロペニル基、２－メチル－２－プロペニル基などのＣ２～６アルケニル基；
　エチニル基、１－プロピニル基、２－プロピニル基、１－ブチニル基、２－ブチニル基、３－ブチニル基、１－メチル－２－プロピニル基などのＣ２～６アルキニル基； The "substituent" is not particularly limited as long as it is chemically permissible and has the effect of the present invention. Examples of groups that can be the "substituent" are shown below.
C1-6 alkyl groups such as a methyl group, an ethyl group, an n-propyl group, an i-propyl group, an n-butyl group, an s-butyl group, an i-butyl group, a t-butyl group, an n-pentyl group, or an n-hexyl group;
C2-6 alkenyl groups such as a vinyl group, a 1-propenyl group, a 2-propenyl group (allyl group), a 1-butenyl group, a 2-butenyl group, a 3-butenyl group, a 1-methyl-2-propenyl group, and a 2-methyl-2-propenyl group;
C2-6 alkynyl groups such as an ethynyl group, a 1-propynyl group, a 2-propynyl group, a 1-butynyl group, a 2-butynyl group, a 3-butynyl group, or a 1-methyl-2-propynyl group;
　シクロプロピル基、シクロブチル基、シクロペンチル基、シクロヘキシル基などのＣ３～６シクロアルキル基；
　フェニル基、ナフチル基などのＣ６～１０アリール基；
　ベンジル基、フェネチル基などのＣ６～１０アリールＣ１～６アルキル基；
　３～６員ヘテロシクリル基；
　３～６員へテロシクリルＣ１～６アルキル基； C3-6 cycloalkyl groups such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group;
C6-10 aryl groups such as phenyl groups and naphthyl groups;
C6-10 aryl C1-6 alkyl groups such as a benzyl group and a phenethyl group;
3- to 6-membered heterocyclyl groups;
3-6 membered heterocyclyl C1-6 alkyl group;
　水酸基；
　メトキシ基、エトキシ基、ｎ－プロポキシ基、ｉ－プロポキシ基、ｎ－ブトキシ基、ｓ－ブトキシ基、ｉ－ブトキシ基、ｔ－ブトキシ基などのＣ１～６アルコキシ基；
　ビニルオキシ基、アリルオキシ基、プロペニルオキシ基、ブテニルオキシ基などのＣ２～６アルケニルオキシ基；
　エチニルオキシ基、プロパルギルオキシ基などのＣ２～６アルキニルオキシ基；
　フェノキシ基、ナフトキシ基などのＣ６～１０アリールオキシ基；
　ベンジルオキシ基、フェネチルオキシ基などのＣ６～１０アリールＣ１～６アルコキシ基；
　チアゾリルオキシ基、ピリジルオキシ基などの５～６員ヘテロアリールオキシ基；
　チアゾリルメチルオキシ基、ピリジルメチルオキシ基などの５～６員ヘテロアリールＣ１～６アルキルオキシ基； Hydroxyl group;
C1-6 alkoxy groups such as a methoxy group, an ethoxy group, an n-propoxy group, an i-propoxy group, an n-butoxy group, an s-butoxy group, an i-butoxy group, or a t-butoxy group;
C2-6 alkenyloxy groups such as a vinyloxy group, an allyloxy group, a propenyloxy group, or a butenyloxy group;
C2-6 alkynyloxy groups such as ethynyloxy groups, propargyloxy groups, etc.;
C6-10 aryloxy groups such as a phenoxy group and a naphthoxy group;
C6-10 aryl C1-6 alkoxy groups such as a benzyloxy group and a phenethyloxy group;
5- to 6-membered heteroaryloxy groups such as thiazolyloxy groups and pyridyloxy groups;
5-6 membered heteroaryl C1-6 alkyloxy groups such as a thiazolylmethyloxy group and a pyridylmethyloxy group;
　ホルミル基；
　アセチル基、プロピオニル基などのＣ１～６アルキルカルボニル基；
　ホルミルオキシ基；
　アセチルオキシ基、プロピオニルオキシ基などのＣ１～６アルキルカルボニルオキシ基；
　ベンゾイル基などのＣ６～１０アリールカルボニル基；
　メトキシカルボニル基、エトキシカルボニル基、ｎ－プロポキシカルボニル基、ｉ－プロポキシカルボニル基、ｎ－ブトキシカルボニル基、ｔ－ブトキシカルボニル基などのＣ１～６アルコキシカルボニル基；
　メトキシカルボニルオキシ基、エトキシカルボニルオキシ基、ｎ－プロポキシカルボニルオキシ基、ｉ－プロポキシカルボニルオキシ基、ｎ－ブトキシカルボニルオキシ基、ｔ－ブトキシカルボニルオキシ基などのＣ１～６アルコキシカルボニルオキシ基；
　カルボキシル基； Formyl group;
C1-6 alkylcarbonyl groups such as acetyl group and propionyl group;
Formyloxy group;
C1-6 alkylcarbonyloxy groups such as an acetyloxy group or a propionyloxy group;
C6-10 arylcarbonyl groups such as a benzoyl group;
C1-6 alkoxycarbonyl groups such as a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an i-propoxycarbonyl group, an n-butoxycarbonyl group, or a t-butoxycarbonyl group;
C1-6 alkoxycarbonyloxy groups such as a methoxycarbonyloxy group, an ethoxycarbonyloxy group, an n-propoxycarbonyloxy group, an i-propoxycarbonyloxy group, an n-butoxycarbonyloxy group, or a t-butoxycarbonyloxy group;
Carboxyl group;
　フルオロ基、クロロ基、ブロモ基、イオド基などのハロゲノ基；
　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、２，２，２－トリフルオロエチル基、ペンタフルオロエチル基、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、パーフルオロプロピル基、２，２，２－トリフルオロ－１－トリフルオロメチルエチル基、パーフルオロイソプロピル基、４－フルオロブチル基、２，２，３，３，４，４，４－ヘプタフルオロブチル基、パーフルオロブチル基、パーフルオロペンチル基、パーフルオロヘキシル基、クロロメチル基、ブロモメチル基、ジクロロメチル基、ジブロモメチル基、トリクロロメチル基、トリブロモメチル基、１－クロロエチル基、２，２，２－トリクロロエチル基、４－クロロブチル基、パークロロヘキシル基、２，４，６－トリクロロヘキシル基などのＣ１～６ハロアルキル基；
　２－クロロ－１－プロペニル基、２－フルオロ－１－ブテニル基などのＣ２～６ハロアルケニル基；
　４，４－ジクロロ－１－ブチニル基、４－フルオロ－１－ペンチニル基、５－ブロモ－２－ペンチニル基などのＣ２～６ハロアルキニル基；
　トリフルオロメトキシ基、２－クロロ－ｎ－プロポキシ基、２，３－ジクロロブトキシ基などのＣ１～６ハロアルコキシ基；
　２－クロロプロペニルオキシ基、３－ブロモブテニルオキシ基などのＣ２～６ハロアルケニルオキシ基；
　クロロアセチル基、トリフルオロアセチル基、トリクロロアセチル基などのＣ１～６ハロアルキルカルボニル基； halogeno groups such as a fluoro group, a chloro group, a bromo group, or an iodo group;
C1-6 haloalkyl groups such as a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a 2,2,2-trifluoroethyl group, a pentafluoroethyl group, a 3,3,3-trifluoropropyl group, a 2,2,3,3,3-pentafluoropropyl group, a perfluoropropyl group, a 2,2,2-trifluoro-1-trifluoromethylethyl group, a perfluoroisopropyl group, a 4-fluorobutyl group, a 2,2,3,3,4,4,4-heptafluorobutyl group, a perfluorobutyl group, a perfluoropentyl group, a perfluorohexyl group, a chloromethyl group, a bromomethyl group, a dichloromethyl group, a dibromomethyl group, a trichloromethyl group, a tribromomethyl group, a 1-chloroethyl group, a 2,2,2-trichloroethyl group, a 4-chlorobutyl group, a perchlorohexyl group, and a 2,4,6-trichlorohexyl group;
C2-6 haloalkenyl groups such as a 2-chloro-1-propenyl group and a 2-fluoro-1-butenyl group;
C2-6 haloalkynyl groups such as a 4,4-dichloro-1-butynyl group, a 4-fluoro-1-pentynyl group, or a 5-bromo-2-pentynyl group;
C1-6 haloalkoxy groups such as a trifluoromethoxy group, a 2-chloro-n-propoxy group, or a 2,3-dichlorobutoxy group;
C2-6 haloalkenyloxy groups such as a 2-chloropropenyloxy group, a 3-bromobutenyloxy group, etc.;
C1-6 haloalkylcarbonyl groups such as a chloroacetyl group, a trifluoroacetyl group, or a trichloroacetyl group;
　アミノ基；
　メチルアミノ基、ジメチルアミノ基、ジエチルアミノ基などのＣ１～６アルキル置換アミノ基；
　アニリノ基、ナフチルアミノ基などのＣ６～１０アリールアミノ基；
　ベンジルアミノ基、フェネチルアミノ基などのＣ６～１０アリールＣ１～６アルキルアミノ基；
　ホルミルアミノ基；
　アセチルアミノ基、プロパノイルアミノ基、ブチリルアミノ基、ｉ－プロピルカルボニルアミノ基などのＣ１～６アルキルカルボニルアミノ基；
　メトキシカルボニルアミノ基、エトキシカルボニルアミノ基、ｎ－プロポキシカルボニルアミノ基、ｉ－プロポキシカルボニルアミノ基などのＣ１～６アルコキシカルボニルアミノ基；
　アミノカルボニル基、ジメチルアミノカルボニル基、フェニルアミノカルボニル基、Ｎ－フェニル－Ｎ－メチルアミノカルボニル基などの無置換もしくは置換基を有するアミノカルボニル基；
　イミノメチル基、（１－イミノ）エチル基、（１－イミノ）－ｎ－プロピル基などのイミノＣ１～６アルキル基；
　Ｎ－ヒドロキシ－イミノメチル基、（１－（Ｎ－ヒドロキシ）－イミノ）エチル基、（１－（Ｎ－ヒドロキシ）－イミノ）プロピル基、Ｎ－メトキシ－イミノメチル基、（１－（Ｎ－メトキシ）－イミノ）エチル基などの置換もしくは無置換のＮ－ヒドロキシイミノＣ１～６アルキル基；
　メトキシイミノ基、エトキシイミノ基、ｎ－プロポキシイミノ基、ｉ－プロポキシイミノ基、ｎ－ブトキシイミノ基などのＣ１～６アルコキシイミノ基；
　アミノカルボニルオキシ基；
　エチルアミノカルボニルオキシ基、ジメチルアミノカルボニルオキシ基などのＣ１～６アルキル置換アミノカルボニルオキシ基； Amino group;
C1-6 alkyl-substituted amino groups such as methylamino group, dimethylamino group, and diethylamino group;
C6-10 arylamino groups such as anilino group and naphthylamino group;
C6-10 aryl C1-6 alkylamino groups such as a benzylamino group or a phenethylamino group;
Formylamino group;
C1-6 alkylcarbonylamino groups such as an acetylamino group, a propanoylamino group, a butyrylamino group, or an i-propylcarbonylamino group;
C1-6 alkoxycarbonylamino groups such as a methoxycarbonylamino group, an ethoxycarbonylamino group, an n-propoxycarbonylamino group, or an i-propoxycarbonylamino group;
unsubstituted or substituted aminocarbonyl groups, such as an aminocarbonyl group, a dimethylaminocarbonyl group, a phenylaminocarbonyl group, or an N-phenyl-N-methylaminocarbonyl group;
imino C1-6 alkyl group such as an iminomethyl group, a (1-imino)ethyl group, or a (1-imino)-n-propyl group;
substituted or unsubstituted N-hydroxyimino C1-6 alkyl groups such as an N-hydroxy-iminomethyl group, a (1-(N-hydroxy)-imino)ethyl group, a (1-(N-hydroxy)-imino)propyl group, an N-methoxy-iminomethyl group, or a (1-(N-methoxy)-imino)ethyl group;
C1-6 alkoxyimino groups, such as a methoxyimino group, an ethoxyimino group, an n-propoxyimino group, an i-propoxyimino group, or an n-butoxyimino group;
Aminocarbonyloxy group;
C1-6 alkyl-substituted aminocarbonyloxy groups such as an ethylaminocarbonyloxy group and a dimethylaminocarbonyloxy group;
　メルカプト基；
　メチルチオ基、エチルチオ基、ｎ－プロピルチオ基、ｉ－プロピルチオ基、ｎ－ブチルチオ基、ｉ－ブチルチオ基、ｓ－ブチルチオ基、ｔ－ブチルチオ基などのＣ１～６アルキルチオ基；
　トリフルオロメチルチオ基、２，２，２－トリフルオロエチルチオ基などのＣ１～６ハロアルキルチオ基；
　フェニルチオ基、ナフチルチオ基などのＣ６～１０アリールチオ基；
　チアゾリルチオ基、ピリジルチオ基などの５～６員ヘテロアリールチオ基； Mercapto group;
C1-6 alkylthio groups, such as a methylthio group, an ethylthio group, an n-propylthio group, an i-propylthio group, an n-butylthio group, an i-butylthio group, an s-butylthio group, or a t-butylthio group;
C1-6 haloalkylthio groups such as a trifluoromethylthio group, a 2,2,2-trifluoroethylthio group, etc.;
C6-10 arylthio groups such as a phenylthio group and a naphthylthio group;
5- to 6-membered heteroarylthio groups, such as thiazolylthio groups and pyridylthio groups;
　メチルスルフィニル基、エチルスルフィニル基、ｔ－ブチルスルフィニル基などのＣ１～６アルキルスルフィニル基；
　トリフルオロメチルスルフィニル基、２，２，２－トリフルオロエチルスルフィニル基などのＣ１～６ハロアルキルスルフィニル基；
　フェニルスルフィニル基などのＣ６～１０アリールスルフィニル基；
　チアゾリルスルフィニル基、ピリジルスルフィニル基などの５～６員ヘテロアリールスルフィニル基； C1-6 alkylsulfinyl groups such as a methylsulfinyl group, an ethylsulfinyl group, or a t-butylsulfinyl group;
C1-6 haloalkylsulfinyl groups such as a trifluoromethylsulfinyl group or a 2,2,2-trifluoroethylsulfinyl group;
C6-10 arylsulfinyl groups such as a phenylsulfinyl group;
5- to 6-membered heteroarylsulfinyl groups such as thiazolylsulfinyl groups and pyridylsulfinyl groups;
　メチルスルホニル基、エチルスルホニル基、ｔ－ブチルスルホニル基などのＣ１～６アルキルスルホニル基；
　トリフルオロメチルスルホニル基、２，２，２－トリフルオロエチルスルホニル基などのＣ１～６ハロアルキルスルホニル基；
　フェニルスルホニル基などのＣ６～１０アリールスルホニル基；
　チアゾリルスルホニル基、ピリジルスルホニル基などの５～６員ヘテロアリールスルホニル基；
　メチルスルホニルオキシ基、エチルスルホニルオキシ基、ｔ－ブチルスルホニルオキシ基などのＣ１～６アルキルスルホニルオキシ基；
　トリフルオロメチルスルホニルオキシ基、２，２，２－トリフルオロエチルスルホニルオキシ基などのＣ１～６ハロアルキルスルホニルオキシ基； C1-6 alkylsulfonyl groups such as a methylsulfonyl group, an ethylsulfonyl group, or a t-butylsulfonyl group;
C1-6 haloalkylsulfonyl groups such as a trifluoromethylsulfonyl group or a 2,2,2-trifluoroethylsulfonyl group;
C6-10 arylsulfonyl groups such as a phenylsulfonyl group;
5- to 6-membered heteroarylsulfonyl groups such as thiazolylsulfonyl groups and pyridylsulfonyl groups;
C1-6 alkylsulfonyloxy groups such as a methylsulfonyloxy group, an ethylsulfonyloxy group, or a t-butylsulfonyloxy group;
C1-6 haloalkylsulfonyloxy groups such as a trifluoromethylsulfonyloxy group, a 2,2,2-trifluoroethylsulfonyloxy group, etc.;
　トリメチルシリル基、トリエチルシリル基、ｔ－ブチルジメチルシリル基などのトリＣ１～６アルキル置換シリル基；
　トリフェニルシリル基などのトリＣ６～１０アリール置換シリル基；
　シアノ基；
　ニトロ基。 triC1-6 alkyl-substituted silyl groups such as a trimethylsilyl group, a triethylsilyl group, or a t-butyldimethylsilyl group;
triC6-10 aryl-substituted silyl groups such as triphenylsilyl groups;
Cyano group;
Nitro group.
　また、これらの「置換基」は、前記置換基中のいずれかの水素原子が、異なる構造の基で置換されていてもよい。その場合の「置換基」としては、Ｃ１～６アルキル基、Ｃ１～６ハロアルキル基、Ｃ１～６アルコキシ基、Ｃ１～６ハロアルコキシ基、ハロゲノ基、シアノ基、ニトロ基などを挙げることができる。 Furthermore, any of the hydrogen atoms in these "substituents" may be replaced with a group of a different structure. In that case, examples of the "substituents" include a C1-6 alkyl group, a C1-6 haloalkyl group, a C1-6 alkoxy group, a C1-6 haloalkoxy group, a halogeno group, a cyano group, and a nitro group.
　また、上記の「３～６員ヘテロシクリル基」は、窒素原子、酸素原子および硫黄原子からなる群から選ばれる１～４個のヘテロ原子を環の構成原子として含む。「３～６員ヘテロシクリル基」としては、３～６員飽和ヘテロシクリル基、５～６員部分不飽和ヘテロシクリル基、５～６員ヘテロアリール基などを挙げることができる。
　３～６員飽和ヘテロシクリル基としては、アジリジニル基、エポキシ基、ピロリジニル基、テトラヒドロフラニル基、チアゾリジニル基、ピペリジル基、ピペラジニル基、モルホリニル基、ジオキソラニル基、ジオキサニル基などを挙げることができる。
　５員部分不飽和へテロシクリル基としては、ピロリニル基、ジヒドロフラニル基、イミダゾリニル基、ピラゾリニル基、オキサゾリニル基、イソオキサゾリニル基などを挙げることができる。
　６員部分不飽和ヘテロシクリル基としては、ジヒドロピラニル基などを挙げることができる。
　５員ヘテロアリール基としては、ピロリル基、フリル基、チエニル基、イミダゾリル基、ピラゾリル基、オキサゾリル基、イソオキサゾリル基、チアゾリル基、イソチアゾリル基、トリアゾリル基、オキサジアゾリル基、チアジアゾリル基、テトラゾリル基などを挙げることができる。
　６員ヘテロアリール基としては、ピリジル基、ピラジニル基、ピリミジニル基、ピリダジニル基、トリアジニル基などを挙げることができる。 The above "3- to 6-membered heterocyclyl group" contains 1 to 4 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur atoms as ring-constituting atoms. Examples of the "3- to 6-membered heterocyclyl group" include 3- to 6-membered saturated heterocyclyl groups, 5- to 6-membered partially unsaturated heterocyclyl groups, and 5- to 6-membered heteroaryl groups.
Examples of the 3- to 6-membered saturated heterocyclyl group include an aziridinyl group, an epoxy group, a pyrrolidinyl group, a tetrahydrofuranyl group, a thiazolidinyl group, a piperidyl group, a piperazinyl group, a morpholinyl group, a dioxolanyl group, and a dioxanyl group.
Examples of the 5-membered partially unsaturated heterocyclyl group include a pyrrolinyl group, a dihydrofuranyl group, an imidazolinyl group, a pyrazolinyl group, an oxazolinyl group, and an isoxazolinyl group.
Examples of the six-membered partially unsaturated heterocyclyl group include a dihydropyranyl group.
Examples of the 5-membered heteroaryl group include a pyrrolyl group, a furyl group, a thienyl group, an imidazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an isothiazolyl group, a triazolyl group, an oxadiazolyl group, a thiadiazolyl group, and a tetrazolyl group.
Examples of the 6-membered heteroaryl group include a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, and a triazinyl group.
〔Ａ１〕
　式（Ｉ）中、Ａ１は、窒素原子、またはＣＨで表される基を示す。 [A 1 ]
In formula (I), A 1 represents a nitrogen atom or a group represented by CH.
〔Ｒ１〕
　式（Ｉ）中、Ｒ１は、Ｃ１～６ハロアルコキシ基、またはＣ１～６ハロアルキルチオ基を示す。
　「Ｃ１～６ハロアルコキシ基」としては、ジフルオロメトキシ基、トリフルオロメトキシ基；　２，２－ジフルオロエトキシ基、２，２，２－トリフルオロエトキシ基、１，１，２，２－テトラフルオロエトキシ基、ペンタフルオロエトキシ基；　３，３－ジ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、１，２，２，３，３，３－ヘキサフルオロプロポキシ基、パーフルオロプロポキシ基；　２，２，２－トリフルオロ－１－トリフルオロメチルエトキシ基、パーフルオロイソプロポキシ基；　２，２，３，３，４，４，４－ヘプタフルオロブトキシ基、１，２，２，３，３，４，４，４－オクタフルオロブトキシ基、パーフルオロブトキシ基；　３，３，３－トリフルオロ－２－トリフルオロメチルプロポキシ基、１－クロロ－２，３，３，３－テトラフルオロ－２－トリフルオロメチルプロポキシ基、１，２，３，３，３－ペンタフルオロ－２－トリフルオロメチルプロポキシ基；　２，２，３，３，４，４，５，５，５－ノナフルオロペンチルオキシ基、１－クロロ－２，２，３，３，４，４，５，５，５－ノナフルオロペンチルオキシ基、１，２，２，３，３，４，４，５，５，５－デカフルオロペンチルオキシ基、パーフルオロペンチルオキシ基；　パーフルオロヘキシルオキシ基；　２，２，２－トリクロロエトキシ基、３，３，３－トリクロロプロポキシ基などを挙げることができる。 [R 1 ]
In formula (I), R 1 represents a C1-6 haloalkoxy group or a C1-6 haloalkylthio group.
Examples of the "C1-6 haloalkoxy group" include a difluoromethoxy group, a trifluoromethoxy group; a 2,2-difluoroethoxy group, a 2,2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, a pentafluoroethoxy group; a 3,3-difluoropropoxy group, a 3,3,3-trifluoropropoxy group, a 2,2,3,3,3-pentafluoropropoxy group, a 1,2,2,3,3,3-hexafluoropropoxy group, a perfluoropropoxy group; a 2,2,2-trifluoro-1-trifluoromethylethoxy group, a perfluoroisopropoxy group; a 2,2,3,3,4,4,4-heptafluorobutoxy group, a 1,2,2,3,3,4,4,4-octafluorobutoxy group, a perfluorobutoxy group; Examples of the alkyl group include a 3,3,3-trifluoro-2-trifluoromethylpropoxy group, a 1-chloro-2,3,3,3-tetrafluoro-2-trifluoromethylpropoxy group, a 1,2,3,3,3-pentafluoro-2-trifluoromethylpropoxy group, a 2,2,3,3,4,4,5,5,5-nonafluoropentyloxy group, a 1-chloro-2,2,3,3,4,4,5,5,5-nonafluoropentyloxy group, a 1,2,2,3,3,4,4,5,5,5-decafluoropentyloxy group, a perfluoropentyloxy group, a perfluorohexyloxy group, a 2,2,2-trichloroethoxy group, and a 3,3,3-trichloropropoxy group.
　「Ｃ１～６ハロアルキルチオ基」としては、ジフルオロメチルチオ基、トリフルオロメチルチオ基；　２，２－ジフルオロエチルチオ基、２，２，２－トリフルオロエチルチオ基、１，１，２，２－テトラフルオロエチルチオ基、ペンタフルオロエチルチオ基；　３，３－ジフルオロプロピルチオ基、３，３，３－トリフルオロプロピルチオ基、２，２，３，３，３－ペンタフルオロプロピルチオ基、１，２，２，３，３，３－ヘキサフルオロプロピルチオ基、パーフルオロプロピルチオ基；　２，２，２－トリフルオロ－１－トリフルオロメチルエチルチオ基、パーフルオロイソプロピルチオ基；　２，２，３，３，４，４，４－ヘプタフルオロブチルチオ基、１，２，２，３，３，４，４，４－オクタフルオロブチルチオ基、パーフルオロブチルチオ基；　３，３，３－トリフルオロ－２－トリフルオロメチルプロピルチオ基、１－クロロ－２，３，３，３－テトラフルオロ－２－トリフルオロメチルプロピルチオ基、１，２，３，３，３－ペンタフルオロ－２－トリフルオロメチルプロピルチオ基；　２，２，３，３，４，４，５，５，５－ノナフルオロペンチルチオ基、１－クロロ－２，２，３，３，４，４，５，５，５－ノナフルオロペンチルチオ基、１，２，２，３，３，４，４，５，５，５－デカフルオロペンチルチオ基、パーフルオロペンチルチオ基；　パーフルオロヘキシルチオ基；　２，２，２－トリクロロエチルチオ基、３，３，３－トリクロロプロピルチオ基などを挙げることができる。 The "C1-6 haloalkylthio group" includes difluoromethylthio group, trifluoromethylthio group, 2,2-difluoroethylthio group, 2,2,2-trifluoroethylthio group, 1,1,2,2-tetrafluoroethylthio group, pentafluoroethylthio group, 3,3-difluoropropylthio group, 3,3,3-trifluoropropylthio group, 2,2,3,3,3-pentafluoropropylthio group, 1,2,2,3,3,3-hexafluoropropylthio group, perfluoropropylthio group, 2,2,2-trifluoro-1-trifluoromethylethylthio group, perfluoroisopropylthio group, 2,2,3,3,4,4,4-heptafluorobutylthio group, 1,2,2,3,3,4,4,4-octafluoropropylthio group, Examples include fluorobutylthio group, perfluorobutylthio group; 3,3,3-trifluoro-2-trifluoromethylpropylthio group, 1-chloro-2,3,3,3-tetrafluoro-2-trifluoromethylpropylthio group, 1,2,3,3,3-pentafluoro-2-trifluoromethylpropylthio group; 2,2,3,3,4,4,5,5,5-nonafluoropentylthio group, 1-chloro-2,2,3,3,4,4,5,5,5-nonafluoropentylthio group, 1,2,2,3,3,4,4,5,5,5-decafluoropentylthio group, perfluoropentylthio group; perfluorohexylthio group; 2,2,2-trichloroethylthio group, 3,3,3-trichloropropylthio group, etc.
　Ｒ１としては、ジフルオロメトキシ基、トリフルオロメトキシ基、２，２－ジフルオロエトキシ基、２，２，２－トリフルオロエトキシ基、１，１，２，２－テトラフルオロエトキシ基、ペンタフルオロエトキシ基などのＣ１～２フルオロアルコキシ基；　ジフルオロメチルチオ基、トリフルオロメチルチオ基、２，２－ジフルオロエチルチオ基、２，２，２－トリフルオロエチルチオ基、１，１，２，２－テトラフルオロエチルチオ基、ペンタフルオロエチルチオ基などのＣ１～２フルオロアルキルチオ基が好ましい。
　さらには、Ｒ１としては、２，２，２－トリフルオロエトキシ基、１，１，２，２－テトラフルオロエトキシ基、トリフルオロメチルチオ基が好ましい。 R1 is preferably a C1-2 fluoroalkoxy group such as a difluoromethoxy group, a trifluoromethoxy group, a 2,2-difluoroethoxy group, a 2,2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, or a pentafluoroethoxy group; or a C1-2 fluoroalkylthio group such as a difluoromethylthio group, a trifluoromethylthio group, a 2,2-difluoroethylthio group, a 2,2,2-trifluoroethylthio group, a 1,1,2,2-tetrafluoroethylthio group, or a pentafluoroethylthio group.
Furthermore, R 1 is preferably a 2,2,2-trifluoroethoxy group, a 1,1,2,2-tetrafluoroethoxy group, or a trifluoromethylthio group.
〔Ｒａ〕
　式（Ｉ）中、Ｒaは、水素原子、または置換若しくは無置換のＣ３～６シクロアルキル基を示す。
　「Ｃ３～６シクロアルキル基」としては、シクロプロピル基、シクロブチル基、シクロペンチル基、シクロヘキシル基などを挙げることができる。
　「Ｃ３～６シクロアルキル基」上の置換基としては、フルオロ基、クロロ基、ブロモ基、イオド基などのハロゲノ基；　水酸基；　メトキシ基、エトキシ基、ｎ－プロポキシ基、ｉ－プロポキシ基、ｎ－ブトキシ基、ｓ－ブトキシ基、ｉ－ブトキシ基、ｔ－ブトキシ基などのＣ１～６アルコキシ基；　２－クロロ－ｎ－プロポキシ基、２，３－ジクロロブトキシ基、トリフルオロメトキシ基などのＣ１～６ハロアルコキシ基；　フェニル基；　４－クロロフェニル基、４－トリフルオロメチルフェニル基、４－トリフルオロメトキシフェニル基などの、「ハロゲノ基、Ｃ１～６ハロアルキル基、若しくはＣ１～６ハロアルコキシ基で置換されたフェニル基」；　またはシアノ基；　が好ましい。 [R a ]
In formula (I), R a represents a hydrogen atom, or a substituted or unsubstituted C3-6 cycloalkyl group.
Examples of the "C3-6 cycloalkyl group" include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.
Preferred substituents on a "C3 to 6 cycloalkyl group" are: a halogeno group such as a fluoro group, a chloro group, a bromo group or an iodo group; a hydroxyl group; a C1 to 6 alkoxy group such as a methoxy group, an ethoxy group, an n-propoxy group, an i-propoxy group, an n-butoxy group, an s-butoxy group, an i-butoxy group or a t-butoxy group; a C1 to 6 haloalkoxy group such as a 2-chloro-n-propoxy group, a 2,3-dichlorobutoxy group or a trifluoromethoxy group; a phenyl group; a "phenyl group substituted with a halogeno group, a C1 to 6 haloalkyl group or a C1 to 6 haloalkoxy group" such as a 4-chlorophenyl group, a 4-trifluoromethylphenyl group or a 4-trifluoromethoxyphenyl group; or a cyano group.
〔Ｂ１、Ｂ２〕
　式（Ｉ）中、Ｂ１は、窒素原子、またはＣＨで表される基を示し、Ｂ２は、窒素原子、またはＣＸｂで表される基を示す。 [ B1 , B2 ]
In formula (I), B 1 represents a nitrogen atom or a group represented by CH, and B 2 represents a nitrogen atom or a group represented by CX b .
〔Ｘａ、Ｘｂ〕
　式（Ｉ）中、ＸａおよびＸｂは、それぞれ独立に、水素原子、ハロゲノ基、Ｃ１～６ハロアルコキシ基、カルバモイル基、チオカルバモイル基、またはシアノ基を示す。
　「ハロゲノ基」としては、フルオロ基、クロロ基、ブロモ基、イオド基などを挙げることができる。
　「Ｃ１～６ハロアルコキシ基」としては、Ｒ１で例示したものと同様の基を挙げることができる。 [ Xa , Xb ]
In formula (I), Xa and Xb each independently represent a hydrogen atom, a halogeno group, a C1-6 haloalkoxy group, a carbamoyl group, a thiocarbamoyl group, or a cyano group.
Examples of the "halogeno group" include a fluoro group, a chloro group, a bromo group, and an iodo group.
Examples of the "C1-6 haloalkoxy group" include the same groups as those exemplified for R1 .
　本実施形態の化合物（Ｉ）の塩は、農園芸学的に許容される塩であれば、特に制限されない。化合物（Ｉ）の塩としては、例えば、塩酸、硫酸などの無機酸の塩；　酢酸、乳酸などの有機酸の塩；リチウム、ナトリウム、カリウムなどのアルカリ金属の塩；カルシウム、マグネシウムなどのアルカリ土類金属の塩；鉄、銅などの遷移金属の塩；アンモニアの塩；トリエチルアミン、トリブチルアミン、ピリジン、ヒドラジンなどの有機塩基の塩などを挙げることができる。 The salt of compound (I) in this embodiment is not particularly limited as long as it is an agriculturally and horticulturally acceptable salt. Examples of salts of compound (I) include salts of inorganic acids such as hydrochloric acid and sulfuric acid; salts of organic acids such as acetic acid and lactic acid; salts of alkali metals such as lithium, sodium, and potassium; salts of alkaline earth metals such as calcium and magnesium; salts of transition metals such as iron and copper; salts of ammonia; and salts of organic bases such as triethylamine, tributylamine, pyridine, and hydrazine.
　本実施形態の化合物（Ｉ）の製造方法は特に限定されない。例えば、化合物（Ｉ）は、実施例等に記載した公知の反応を利用した製造方法によって得ることができる。例えば、特許文献１に記載の製法などにより得ることができる。
　化合物（Ｉ）の塩は、化合物（Ｉ）から公知の手法によって得ることができる。
　本実施形態の化合物（Ｉ）は、例えば、以下に示す反応スキームに示すような反応を利用することにより得ることができる。
（反応スキーム１）
　式(I-1)で表わされる化合物と式(I-2)で表される化合物との反応によって、化合物（Ｉ）を得ることができる。この反応は、塩基若しくは触媒の存在下で行うことができる。 The method for producing the compound (I) of the present embodiment is not particularly limited. For example, the compound (I) can be obtained by a production method utilizing a known reaction described in the Examples, etc. For example, it can be obtained by the production method described in Patent Document 1.
The salt of compound (I) can be obtained from compound (I) by a known method.
Compound (I) of the present embodiment can be obtained, for example, by utilizing a reaction as shown in the reaction scheme below.
(Reaction Scheme 1)
Compound (I) can be obtained by reacting a compound represented by formula (I-1) with a compound represented by formula (I-2). This reaction can be carried out in the presence of a base or a catalyst.
Figure JPOXMLDOC01-appb-C000005
Figure JPOXMLDOC01-appb-C000005
　式(I-1)、式(I-2)中の記号は、式(I)中のそれらと同じ意味を示す。
（反応スキーム２）
　式(I-3)で表わされる化合物と式(I-2)で表される化合物とトリホスゲンとの反応によって、化合物（Ｉ）を得ることができる。 The symbols in formulae (I-1) and (I-2) have the same meanings as those in formula (I).
(Reaction Scheme 2)
Compound (I) can be obtained by reacting a compound represented by formula (I-3) and a compound represented by formula (I-2) with triphosgene.
Figure JPOXMLDOC01-appb-C000006
Figure JPOXMLDOC01-appb-C000006
　式(I-3)中の記号は、各々、式(I)中のそれらと同じ意味を示す。 The symbols in formula (I-3) each have the same meaning as those in formula (I).
〔殺虫剤〕
　本発明の第２の実施形態は、前記第１の実施形態の化合物（Ｉ）またはその塩から選ばれる少なくともひとつを有効成分として含有する殺虫剤である。本実施形態の殺虫剤に含まれる前記（ヘテロ）アリールウレア化合物の量は殺虫効果を示す限りにおいて特に制限されない。
　また、本実施形態の（ヘテロ）アリールウレア化合物は、作物に対する薬害が少なく、魚類や温血動物への毒性が低いため、安全性の高い物質である。そのため、殺虫剤の有効成分として有用である。
　さらに、近年、コナガ、ウンカ、ヨコバイ、アブラムシなど多くの害虫において各種既存薬剤に対する抵抗性が発達し、それら薬剤の効力不足問題を生じており、抵抗性系統の害虫にも有効な薬剤が望まれている。本実施形態の（ヘテロ）アリールウレア化合物は、感受性系統のみならず、各種抵抗性系統の害虫にも優れた防除効果を示す。
　また、本実施形態の（ヘテロ）アリールウレア化合物（以下、本発明化合物ということがある。）は、防除の対象となる生物のすべての発育ステージにおいて効力を示し、例えば、ダニ、昆虫などの卵、若虫、幼虫、蛹、成虫に対して優れた防除効果を示す。 〔Insecticide〕
The second embodiment of the present invention is an insecticide containing at least one selected from the compound (I) of the first embodiment or a salt thereof as an active ingredient. The amount of the (hetero)aryl urea compound contained in the insecticide of this embodiment is not particularly limited as long as it shows an insecticidal effect.
In addition, the (hetero)aryl urea compound of the present embodiment is a highly safe substance because it has little phytotoxicity to crops and low toxicity to fish and warm-blooded animals, and is therefore useful as an active ingredient of insecticides.
Furthermore, in recent years, many pests, such as diamondback moths, planthoppers, leafhoppers, and aphids, have developed resistance to various existing pesticides, causing problems with the efficacy of these pesticides, and there is a demand for pesticides that are effective against resistant pests. The (hetero)aryl urea compound of the present embodiment exhibits excellent control effects not only against susceptible pests, but also against various resistant pests.
In addition, the (hetero)aryl urea compound of the present embodiment (hereinafter, sometimes referred to as the compound of the present invention) is effective against all developmental stages of organisms to be controlled, and exhibits excellent control effects against, for example, eggs, nymphs, larvae, pupae, and adults of mites, insects, and the like.
　前記第２の実施形態の殺虫剤は、穀物類；野菜類；根菜類；イモ類；花卉類；果樹類；観葉植物、茶、コーヒー、カカオなどの樹木類；牧草類；芝類；ワタなどの植物に対して用いることが好ましい。
　植物への施用において、前記の殺虫剤は、葉、茎、柄、花、蕾、果実、種子、スプラウト、根、塊茎、塊根、苗条、挿し木などのいずれの部位に用いてもよい。
　また、前記の殺虫剤は、施用される植物の種によって特に制限されない。植物の種としては、例えば、原種、変種、改良品種、栽培品種、突然変異体、ハイブリッド体、遺伝子組み換え体（ＧＭＯ）などを挙げることができる。
　前記の殺虫剤は、各種の農業害虫を防除するために、種子処理、茎葉散布、土壌施用、水面施用などに使用することができる。 The insecticide of the second embodiment is preferably used on plants such as grains, vegetables, root vegetables, potatoes, flowers, fruit trees, ornamental plants, trees such as tea, coffee, and cacao, pasture grasses, turf grasses, and cotton.
When applied to plants, the insecticide may be applied to any part of the plant, such as leaves, stems, stalks, flowers, buds, fruits, seeds, sprouts, roots, tubers, tuberous roots, shoots, cuttings, etc.
The insecticide is not particularly limited by the species of the plant to which it is applied, and examples of the species of the plant include original species, varieties, improved varieties, cultivated varieties, mutants, hybrids, genetically modified organisms (GMOs), and the like.
The above insecticides can be used for controlling various agricultural pests by seed treatment, foliage spray, soil application, water surface application, and the like.
　前記第２の実施形態の殺虫剤によって防除可能な各種の農業害虫の具体例を以下に示す。
（１）鱗翅目（Lepidoptera）のチョウまたは蛾
（ａ）ヒトリガ科（Arctiidae）のガ、例えば、アメリカシロヒトリ（Hyphantria cunea）、クワゴマダラヒトリ（Lemyra imparilis）；
（ｂ）チビガ科（Bucculatricidae）のガ、例えば、ナシチビガ（Bucculatrix pyrivorella）；
（ｃ）シンクイガ科（Carposinidae）のガ、例えば、モモシンクイガ（Carposina sasakii）；
（ｄ）ツトガ科（Crambidae）のガ、例えば、ジアファニア属種（Diaphania spp.）の、ワタヘリクロノメイガ（Diaphania indica）、アメリカウリノメイガ （Diaphania nitidalis）；例えば、オストリニア属種（Ostrinia spp.）の、アワノメイガ（Ostrinia furnacalis）、ヨーロピアンコーンボーラー（Ostrinia nubilalis）、アズキノメイガ（Ostrinia scapulalis）；その他、ニカメイガ（Chilo suppressalis）、コブノメイガ（Cnaphalocrocis medinalis）、モモノゴマダラノメイガ（Conogethes punctiferalis）、サウスウエスタンコンボーラー（Diatraea grandiosella）、クワノメイガ（Glyphodes pyloalis）、ハイマダラノメイガ（Hellula undalis）、シバツトガ（Parapediasia teterrella）；
（ｅ）キバガ科（Gelechiidae）のガ、例えば、イモキバガ（Helcystogramma triannulella）、ワタアカミムシ（Pectinophora gossypiella）、ジャガイモキバガ（Phthorimaea operculella）、バクガ（Sitotroga cerealella）；
（ｆ）シャクガ科（Geometridae）のガ、例えば、ヨモギエダシャク（Ascotis selenaria）；
（ｇ）ホソガ科（Gracillariidae）のガ、例えば、チャノホソガ（Caloptilia theivora）、ミカンハモグリガ（Phyllocnistis citrella）、キンモンホソガ（Phyllonorycter ringoniella）；
（ｈ）セセリチョウ科（Hesperiidae）のチョウ、例えば、イチモンジセセリ（Parnara guttata）；
（ｉ）カレハガ科（Lasiocampidae）のガ、例えば、オビカレハ（Malacosoma neustria）；
（ｊ）ドクガ科（Lymantriidae）のガ、例えば、リマントリア属種（Lymantria spp.）の、マイマイガ（Lymantria dispar）、ノンネマイマイ（Lymantria monacha）；その他の、チャドクガ（Euproctis pseudoconspersa）、ヒメシロモンドクガ（Orgyia thyellina）；
（ｋ）モグリガ科（Lyonetiidae ）のガ、例えば、リオネチア属種（Lyonetia spp.）の、モモハモグリガ（Lyonetia clerkella）、ギンモンハモグリガ（Lyonetia prunifoliella malinella）；
（ｌ）ヤガ科（Noctuidae）のガ、例えば、スポドプテラ属種（Spodoptera spp.）の、スジキリヨトウ（Spodoptera depravata）、サザンアーミーワーム（Spodoptera eridania）、シロイチモジヨトウ（Spodoptera exigua）、ツマジロクサヨトウ（Spodoptera frugiperda）、アフリカヨトウ（Spodoptera littoralis）、ハスモンヨトウ（Spodoptera litura）；例えば、オートグラファ属種（Autographa spp.）の、ガンマキンウワバ （Autographa gamma）、タマナギンウワバ（Autographa nigrisigna）；例えば、アグロチス属種（Agrotis spp.）の、タマナヤガ（Agrotis ipsilon）、カブラヤガ（Agrotis segetum）；例えば、ヘリコベルパ属種（Helicoverpa spp.）の、オオタバコガ（Helicoverpa armigera）、タバコガ（Helicoverpa assulta）、コットンボールワーム（Helicoverpa zea）；例えば、ヘリオチス属種（Heliothis spp.）の、ワタキバガ （Heliothis armigera）、ニセアメリカタバコガ（Heliothis virescens）；その他の、ナカジロシタバ（Aedia leucomelas）、ミツモンキンウワバ（Ctenoplusia agnata）、アケビコノハ（Eudocima tyrannus）、ヨトウガ（Mamestra brassicae）、アワヨトウ（Mythimna separata）、フタオビコヤガ（Naranga aenescens）、マツキリガ（Panolis japonica）、ニセタマナヤガ（Peridroma saucia）、ソイビーンルーパー（Pseudoplusia includens）、イラクサギンウワバ（Trichoplusia ni）；
（ｍ）コブガ科（Nolidae） のガ、例えば、ミスジアオリンガ （Earias insulana）；
（ｎ）シロチョウ科（Pieridae）のチョウ、例えば、モンシロチョウ属種（Pieris spp.）のオオモンシロチョウ（Pieris brassicae）、モンシロチョウ（Pieris rapae crucivora）；
（ｏ）コナガ科（Plutellidae）のガ、例えば、アクロレピオプシス属種（Acrolepiopsis spp.）の、ネギコガ（Acrolepiopsis sapporensis）、ヤマノイモコガ（Acrolepiopsis suzukiella）；その他、コナガ（Plutella xylostella）；
（ｐ）メイガ科（Pyralidae）のガ、例えば、スジマダラメイガ（Cadra cautella）、モロコシマダラメイガ（Elasmopalpus lignosellus）、シロイチモジマダラメイガ（Etiella zinckenella）、ハチノスツヅリガ （Galleria mellonella）；
（ｑ）スズメガ科（Sphingidae）のガ、例えば、マンジュカ属種（Manduca spp.）の、トマトホーンワーム（Manduca quinquemaculata）、タバコホーンワーム（Manduca sexta）；
（ｒ）ニセマイコガ科（Stathmopodidae）のガ、例えば、カキノヘタムシガ（Stathmopoda masinissa）；
（ｓ）ヒロズコガ科（Tineidae）のガ、例えば、イガ（Tinea translucens）；
（ｔ）ハマキガ科（Tortricidae）のガ、例えば、アドキソフィエス属種（Adoxophyes spp.）の、チャノコカクモンハマキ（Adoxophyes honmai）、リンゴコカクモンハマキ（Adoxophyes orana）；例えば、アルチプス属種（Archips spp.）の、リンゴモンハマキ（Archips breviplicanus）、ミダレカクモンハマキ（Archips fuscocupreanus）；その他の、トウヒノシントメハマキ （Choristoneura fumiferana）、コドリンガ（Cydia pomonella）、ブドウホソハマキ （Eupoecilia ambiguella）、ナシヒメシンクイ（Grapholitha molesta）、チャハマキ（Homona magnanima）、マメシンクイガ（Leguminivora glycinivorella）、ホソバヒメハマキ（Lobesia botrana）、マメヒメサヤムシガ（Matsumuraeses phaseoli）、トビハマキ（Pandemis heparana）、テングハマキ（Sparganothis pilleriana）；
（ｕ）スガ科（Yponomeutidae）のガ、例えば、リンゴヒメシンクイ（Argyresthia conjugella）。 Specific examples of various agricultural pests that can be controlled by the insecticide of the second embodiment are shown below.
(1) Butterflies or moths of the order Lepidoptera (a) Arctiidae moths, such as Hyphantria cunea and Lemyra imparilis;
(b) Bucculatricidae moths, for example, Bucculatrix pyrivorella;
(c) moths of the family Carposinidae, for example, the peach fruit moth (Carposina sasakii);
(d) Crambidae moths, for example, Diaphania spp., Diaphania indica, Diaphania nitidalis; for example, Ostrinia spp., Ostrinia furnacalis, Ostrinia nubilalis, Ostrinia scapulalis; others, Chilo suppressalis, Cnaphalocrocis medinalis, Conogethes punctiferalis, Diatraea grandiosella, Glyphodes pyloalis, Hellula undalis), the grass moth (Parapediasia teterrella);
(e) Gelechiidae moths, for example, Helcystogramma triannulella, Pectinophora gossypiella, Phthorimaea operculella, Sitotroga cerealella;
(f) Geometridae moths, for example, Ascotis selenaria;
(G) Gracilaria family moths, for example, Caloptilia theivora, Phyllocnistis citrella, Phyllonorycter ringoniella;
(h) butterflies of the Hesperiidae family, for example, Parnara guttata;
(i) Lasiocampidae moths, for example, Malacosoma neustria;
(j) Lymantriidae moths, for example, Lymantria spp., Lymantria dispar, Lymantria monacha; others, Euproctis pseudoconspersa, Orgyia thyellina;
(K) Lyonetiidae moths, for example, Lyonetia spp., peach leafminer (Lyonetia clerkella), silver leafminer (Lyonetia prunifoliella malinella);
(l) Noctuidae moths, for example, Spodoptera spp., Spodoptera depravata, Spodoptera eridania, Spodoptera exigua, Spodoptera frugiperda, Spodoptera littoralis, Spodoptera litura; for example, Autographa spp., Autographa gamma, Autographa nigrisigna; for example, Agrotis spp., Agrotis ipsilon, Agrotis segetum; for example, Helicoverpa spp. Heliothis spp., for example, Heliothis armigera, Heliothis virescens; others, for example, Aedia leucomelas, Ctenoplusia agnata, Eudocima tyrannus, Mamestra brassicae, Mythimna separata, Naranga aenescens, Panolis japonica, Peridroma saucia, Pseudoplusia includens, Trichoplusia ni);
(m) Nolidae moths, for example, Earias insulana;
(n) Butterflies of the family Pieridae, for example, Pieris spp., Pieris brassicae, Pieris rapae crucivora;
(O) Plutellidae moths, for example, Acrolepiopsis spp., such as Acrolepiopsis sapporensis and Acrolepiopsis suzukiella; others, such as Plutella xylostella;
(p) moths of the family Pyralidae, for example, Cadra cautella, Elasmopalpus lignosellus, Etiella zinckenella, Galleria mellonella;
(q) Sphingidae moths, for example, Manduca spp., tomato hornworm (Manduca quinquemaculata), tobacco hornworm (Manduca sexta);
(R) Stathmopodidae moths, for example, Stathmopoda masinissa;
(s) moths of the family Tineidae, for example, Tinea translucens;
(t) Tortricidae moths, for example, Adoxophyes spp., Adoxophyes honmai, Adoxophyes orana; for example, Archips spp., Archips breviplicanus, Archips fuscocupreanus; other spruce budworm moths, Choristoneura fumiferana, Cydia pomonella, Eupoecilia ambiguella, Grapholitha molesta, Homona magnanima, Leguminivore glycinivorella, Lobesia botrana), Matsumuraeses phaseoli, Pandemis heparana, Sparaganothis pilleriana;
(u) Moths of the family Yponomeutidae, for example, Argyresthia conjugella.
（２）アザミウマ目（Thysanoptera）害虫
（ａ）クダアザミウマ科（Phlaeothripidae）の、例えば、カキクダアザミウマ（Ponticulothrips diospyrosi）；
（ｂ）アザミウマ科（Thripidae）の、例えば、フランクリニェラ属種（Frankliniella spp.）の、ヒラズハナアザミウマ（Frankliniella intonsa）、ミカンキイロアザミウマ（Frankliniella occidentalis）；例えば、トリプス属種（Thrips spp.）の、ミナミキイロアザミウマ（Thrips palmi）、ネギアザミウマ（Thrips tabaci）；その他の、クロトンアザミウマ（Heliothrips haemorrhoidalis）、チャノキイロアザミウマ（Scirtothrips dorsalis）。 (2) Thysanoptera pests (a) Phlaeothripidae, for example, Ponticulothrips diospyrosi;
(b) Thripidae, for example, Frankliniella spp., Frankliniella intonsa, Frankliniella occidentalis; Thrips spp., Thrips palmi, Thrips tabaci; and others, Heliothrips haemorrhoidalis, Scirtothrips dorsalis.
（３）カメムシ目（Hemiptera）の害虫
（Ａ）頸吻亜目（Archaeorrhyncha）
（ａ）ウンカ科（Delphacidae）の、例えば、ヒメトビウンカ（Laodelphax striatella）、トビイロウンカ（Nilaparvata lugens）、クロフツノウンカ（Perkinsiella saccharicida）、セジロウンカ（Sogatella furcifera）。
（Ｂ）頸吻亜目（Clypeorrhyncha）
（ａ）ヨコバイ科（Cicadellidae）の、例えば、エンポアスカ属種（Empoasca spp.）の、ジャガイモヒメヨコバイ（Empoasca fabae）、カキノヒメヨコバイ（Empoasca nipponica）、チャノミドリヒメヨコバイ（Empoasca onukii）、マメノミドリヒメヨコバイ（Empoasca sakaii）；その他の、フタテンヒメヨコバイ（Arboridia apicalis）、ミドリナガヨコバイ（Balclutha saltuella）、フタテンオオヨコバイ（Epiacanthus stramineus）、ヒメフタテンヨコバイ（Macrosteles striifrons）、ツマグロヨコバイ（Nephotettix cinctinceps）。 (3) Pests of the Order Hemiptera (A) Archaeorrhyncha
(A) Delphacidae, for example, Laodelphax striatella, Nilaparvata lugens, Perkinsiella saccharicida, Sogatella furcifera.
(B) Clypeorrhyncha
(A) Cicadellidae, for example, Empoasca spp., potato leafhopper (Empoasca fabae), persimmon leafhopper (Empoasca nipponica), tea green leafhopper (Empoasca onukii), bean green leafhopper (Empoasca sakaii); other, Arboridia apicalis, Balclutha saltuella, Epiacanthus stramineus, Macrosteles striifrons, Nephotettix cinctinceps.
（Ｃ）カメムシ亜目（Heteroptera）
（ａ）ホソヘリカメムシ科（Alydidae）の、例えば、ホソヘリカメムシ（Riptortus clavatus）；
（ｂ）ヘリカメムシ科（Coreidae）の、例えば、ホソハリカメムシ（Cletus punctiger）、クモヘリカメムシ（Leptocorisa chinensis）；
（ｃ）ナガカメムシ科（Lygaeidae）の、例えば、アメリカコバネナガカメムシ （Blissus leucopterus）、カンシャコバネナガカメムシ（Cavelerius saccharivorus）、コバネヒョウタンナガカメムシ（Togo hemipterus）；
（ｄ）カスミカメムシ科（Miridae）の、例えば、クロトビカスミカメ（Halticus insularis）、サビイロカスミカメ （Lygus lineolaris）、コットンフリーホッパー（Psuedatomoscelis seriatus）、ナガムギカスミカメ（Stenodema sibiricum）、アカスジカスミカメ（Stenotus rubrovittatus）、イネホソミドリカスミカメ（Trigonotylus caelestialium）； (C) Heteroptera
(a) Alydidae, for example, Riptortus clavatus;
(b) Coreidae, for example, Cletus punctiger, Leptocorisa chinensis;
(C) Lygaeidae, for example, Blissus leucopterus, Cavelerius saccharivorus, Togo hemipterus;
(D) Miridae, for example, Halticus insularis, Lygus lineolaris, Psuedatomoscelis seriatus, Stenodema sibiricum, Stenotus rubrovittatus, Trigonotylus caelestialium;
（ｅ）カメムシ科（Pentatomidae）の、例えば、ネザラ属種（Nezara spp.）の、アオクサカメムシ（Nezara antennata）、ミナミアオカメムシ（Nezara viridula）；例えば、シラホシカメムシ属種（Eysarcoris spp.）の、トゲシラホシカメムシ（Eysarcoris aeneus）、オオトゲシラホシカメムシ（Eysarcoris lewisi）、シラホシカメムシ（Eysarcoris ventralis）、その他の、ブチヒゲカメムシ（Dolycoris baccarum）、ナガメ（Eurydema rugosum）、ツヤアオカメムシ（Glaucias subpunctatus）、サギカメムシ（Halyomorpha halys）、クイチモンジカメムシ（Piezodorus hybneri）、チャバネアオカメムシ（Plautia crossota）、イネクロカメムシ（Scotinophora lurida）；
（ｆ）ホシカメムシ科（Pyrrhocoridae）の、例えば、アカホシカメムシ（Dysdercus cingulatus）；
（ｇ）ヒメヘリカメムシ科（Rhopalidae）の、例えば、アカヒメヘリカメムシ（Rhopalus msculatus）；
（ｈ）キンカメムシ科（Scutelleridae）の、例えば、ムギチャイロカメムシ（Eurygaster integriceps）；
（ｉ）グンバイムシ科（Tingidae）の、例えば、ナシグンバイ（Stephanitis nashi）。 (e) Pentatomidae, for example, Nezara spp., Nezara antennata, Nezara viridula; for example, Eysarcoris spp., Eysarcoris aeneus, Eysarcoris lewisi, Eysarcoris ventralis, Dolycoris baccarum, Eurydema rugosum, Glaucias subpunctatus, Halyomorpha halys, Piezodorus hybneri), Plautia crossota, Scotinophora lurida;
(F) Pyrrhocoridae, for example, Dysdercus cingulatus;
(G) Rhopalidae, for example, Rhopalus msculatus;
(H) Scutelleridae, for example, Eurygaster integriceps;
(i) Tingidae, for example, Stephanitis nashi.
（Ｄ）腹吻亜目（Sternorrhyncha）
（ａ）カサアブラムシ科（Adelgidae）の、例えば、カラマツカサアブラムシ（Adelges laricis）；
（ｂ）コナジラミ科（Aleyrodidae）例えば、ベミシア属種（Bemisia spp.）の、シルバーリーフコナジラミ（Bemisia argentifolii）、タバココナジラミ（Bemisia tabaci）；その他の、ミカントゲコナジラミ（Aleurocanthus spiniferus）、ミカンコナジラミ（Dialeurodes citri）、オンシツコナジラミ（Trialeurodes vaporariorum）；
（ｃ）アブラムシ科（Aphididae）、例えば、アフィス属種（Aphis spp.）の、マメアブラムシ（Aphis craccivora）、マメクロアブラムシ（Aphis fabae）、イチゴネアブラムシ（Aphis forbesi）、ワタアブラムシ（Aphis gossypii）、ヨーロッパリンゴアブラムシ（Aphis pomi）、ニワトコアブラムシ（Aphis sambuci）、ユキヤナギアブラムシ（Aphis spiraecola）；例えば、ロパロシフム属種（Rhopalosiphum spp.）の、トウモロコシアブラムシ（Rhopalosiphum maidis）、ムギクビレアブラムシ（Rhopalosiphum padi）；例えば、ジサフィス属種（Dysaphis spp.）の、オオバコアブラムシ（Dysaphis plantaginea）、ギシギシネアブラムシ（Dysaphis radicola）；例えば、マクロシフム属種（Macrosiphum spp.）の、ムギヒゲナガアブラムシ（Macrosiphum avenae）、チューリップヒゲナガアブラムシ（Macrosiphum euphorbiae）；例えば、ミズス属種（Myzus spp.）の、ニワウメクロコブアブラムシ （Myzus cerasi）、モモアカアブラムシ（Myzus persicae）、カワリコブアブラムシ（Myzus varians）；その他の、エンドウヒゲナガアブラムシ（Acyrthosiphon pisum）、ジャガイモヒゲナガアブラムシ（Aulacorthum solani）、ムギワラギクオマルアブラムシ（Brachycaudus helichrysi）、ダイコンアブラムシ（Brevicoryne brassicae）、イチゴケナガアブラムシ（Chaetosiphon fragaefolii）、モモコフキアブラムシ（Hyalopterus pruni）、チシャミドリアブラムシ（Hyperomyzus lactucae）、ニセダイコンアブラムシ（Lipaphis erysimi）、ソラマメヒゲナガアブラムシ（Megoura viciae）、ムギウスイロアブラムシ（Metopolophium dirhodum）、レタスアブラムシ（Nasonovia ribis-nigri）、ホップイボアブラムシ（Phorodon humuli）、ムギミドリアブラムシ（Schizaphis graminum）、ムギヒゲナガアブラムシ（Sitobion avenae）、コミカンアブラムシ（Toxoptera aurantii）； (D) Sternorrhyncha
(a) Adelgidae, for example, Adelges laricis;
(b) Aleyrodidae, for example, Bemisia spp., silverleaf whitefly (Bemisia argentifolii), tobacco whitefly (Bemisia tabaci); other, Aleurocanthus spiniferus, Dialeurodes citri, Trialeurodes vaporariorum;
(c) Aphididae, for example, Aphis spp., bean aphid (Aphis craccivora), bean black aphid (Aphis fabae), strawberry aphid (Aphis forbesi), cotton aphid (Aphis gossypii), European apple aphid (Aphis pomi), elder aphid (Aphis sambuci), Yukiyanagi aphid (Aphis spiraecola); for example, Rhopalosiphum spp., corn aphid (Rhopalosiphum maidis), wheat kleptomeria aphid (Rhopalosiphum padi); for example, Dysaphis spp., plantago aphid (Dysaphis plantaginea), Rumex aphid (Dysaphis radicola; Macrosiphum spp., for example Macrosiphum avenae, Macrosiphum euphorbiae; Myzus spp., for example Myzus cerasi, Myzus persicae, Myzus varians; others, Acyrthosiphon pisum, Aulacorthum solani, Brachycaudus helichrysi, Brevicoryne brassicae, Chaetosiphon fragaefolii, Hyalopterus pruni), lettuce aphid (Hyperomyzus lactucae), false radish aphid (Lipaphis erysimi), broad bean aphid (Megoura viciae), wheat aphid (Metopolophium dirhodum), lettuce aphid (Nasonovia ribis-nigri), hop aphid (Phorodon humuli), wheat green aphid (Schizaphis graminum), wheat long aphid (Sitobion avenae), cane aphid (Toxoptera aurantii);
（ｄ）カタカイガラムシ科（Coccidae）の、例えば、セロプラスター属種（Ceroplastes spp.）の、ツノロウムシ（Ceroplastes ceriferus）、ルビーロウムシ（Ceroplastes rubens）；
（ｅ）マルカイガラムシ科（Diaspididae）の、シューダウラカスピス属種（Pseudaulacaspis spp.）の、クワシロカイガラムシ（Pseudaulacaspis pentagona）、ウメシロカイガラムシ（Pseudaulacaspis prunicola）；例えば、ウナスピス属種（Unaspis spp.）の、マサキナガカイガラムシ（Unaspis euonymi）、ヤノネカイガラムシ（Unaspis yanonensis）；その他の、アカマルカイガラムシ（Aonidiella aurantii）、ナシマルカイガラムシ（Comstockaspis perniciosa）、チャコノハカイガラムシ（Fiorinia theae）、チャノマルカイガラムシ（Pseudaonidia paeoniae）；
（ｆ）ワタフキカイガラムシ科（Margarodidae）の、例えば、オオワラジカイガラムシ（Drosicha corpulenta）、イセリアカイガラムシ（Icerya purchasi）；
（ｇ）ネアブラムシ科（Phylloxeridae）の、例えば、ブドウネアブラムシ（Viteus vitifolii）；
（ｈ）コナカイガラムシ科（Pseudococcidae ）の、例えば、プラノコッカス属種（Planococcus spp.）の、ミカンコナカイガラムシ（Planococcus citri）、フジコナカイガラムシ（Planococcus kuraunhiae）；その他の、ナスコナカイガラムシ（Phenacoccus solani）、クワコナカイガラムシ（Pseudococcus comstocki）；
（ｉ）キジラミ科（Psyllidae）の、例えば、プスルラ属種（Psylla spp.）の、リンゴキジラミ（Psylla mali）、ナシキジラミ（Psylla pyrisuga）；その他の、ミカンキジラミ（Diaphorina citri）。 (D) Coccidae, for example, Ceroplastes spp., Ceroplastes ceriferus, Ceroplastes rubens;
(e) Pseudaulacaspis spp. of the family Diaspididae, Pseudaulacaspis pentagona, Pseudaulacaspis prunicola; for example, Unaspis spp. of the family Unaspis, Unaspis euonymi, Unaspis yanonensis; other Aonidiella aurantii, Comstockaspis perniciosa, Fiorinia theae, Pseudaonidia paeoniae;
(F) Margarodidae, for example, Drosicha corpulenta, Icerya purchasi;
(g) Phylloxeridae, for example, Viteus vitifolii;
(h) Pseudococcidae, for example, Planococcus spp., Planococcus citri, Planococcus kuraunhiae; other, Phenacoccus solani, Pseudococcus comstocki;
(i) Psyllidae family, for example, Psylla spp., such as Psylla mali, Psylla pyrisuga; and others, such as Diaphorina citri.
（４）カブトムシ亜目（Polyphaga）の害虫
（ａ）シバンムシ科（Anobiidae）の、例えば、タバコシバンムシ（Lasioderma serricorne）；
（ｂ）オトシブミ科（Attelabidae）の、例えば、ドロハマキチョッキリ（Byctiscus betulae）、モモチョッキリゾウムシ（Rhynchites heros）；
（ｃ）ナガシンクイムシ科（Bostrichidae）の、例えば、ヒラタキクイムシ（Lyctus brunneus）；
（ｄ）ミツギリゾウムシ科（Brentidae）の、例えば、アリモドキゾウムシ（Cylas formicarius）；
（ｅ）タマムシ科（Buprestidae ）の、例えば、アカバナガタマムシ （Agrilus sinuatus）；
（ｆ）カミキリムシ科（Cerambycidae）の、例えば、ゴマダラカミキリ（Anoplophora malasiaca）、マツノマダラカミキリ（Monochamus alternatus）、キボシカミキリ（Psacothea hilaris）、ブドウトラカミキリ（Xylotrechus pyrrhoderus）；
（ｇ）ハムシ科（Chrysomelidae）の、例えば、ブルクス属種（Bruchus spp.）の、エンドウマメゾウムシ （Bruchus pisorum）、ソラマメゾウムシ （Bruchus rufimanus）；例えば、ジアブロチカ属種（Diabrotica spp.）の、ノーザンコーンルートワーム（Diabrotica barberi）、サザンコーンルートワーム（Diabrotica undecimpunctata）、ウエスタンコーンルートワーム（Diabrotica virgifera）；例えば、フィロトレタ属種（Phyllotreta spp.）の、ノミトビヨロイムシ（Phyllotreta nemorum）、キスジノミハムシ（Phyllotreta striolata）；その他の、ウリハムシ（Aulacophora femoralis）、アズキゾウムシ（Callosobruchus chinensis）、カメノコハムシ（Cassida nebulosa）、テンサイトビハムシ（Chaetocnema concinna）、コロラドハムシ（Leptinotarsa decemlineata）、イネクビホソハムシ（Oulema oryzae）、ナスナガスネトビハムシ（Psylliodes angusticollis）； (4) Pests of the suborder Polyphaga (a) of the family Anobiidae, for example, the cigarette beetle (Lasioderma serricorne);
(b) Attelabidae, for example, Byctiscus betulae, Rhynchites heros;
(C) Bostrichidae, for example, Lyctus brunneus;
(d) Brentidae, for example, Cylas formicarius;
(e) Buprestidae, for example, Agrilus sinuatus;
(F) Cerambycidae, for example, Anoplophora malasiaca, Monochamus alternatus, Psacothea hilaris, Xylotrechus pyrrhoderus;
(g) Chrysomelidae, for example, Bruchus spp., pea weevil (Bruchus pisorum), broad bean weevil (Bruchus rufimanus); for example, Diabrotica spp., northern corn rootworm (Diabrotica barberi), southern corn rootworm (Diabrotica undecimpunctata), western corn rootworm (Diabrotica virgifera); for example, Phyllotreta spp., flea beetle (Phyllotreta nemorum), kiss stripe flea beetle (Phyllotreta striolata); other, Aulacophora femoralis, Callosobruchus chinensis, Cassida nebulosa), Chaetocnema concinna, Colorado beetle (Leptinotarsa decemlineata), rice leaf beetle (Oulema oryzae), eggplant long-horned beetle (Psylliodes angusticollis);
（ｈ）テントウムシ科（Coccinellidae）の、例えば、エピラクナ属種（Epilachna spp.）の、インゲンテントウ（Epilachna varivestis）、ニジュウヤホシテントウ（Epilachna vigintioctopunctata）；
（ｉ）ゾウムシ科（Curculionidae）の、例えば、アントノムス属種（Anthonomus spp.）の、ワタミゾウムシ（Anthonomus grandis）、ナシハナゾウムシ （Anthonomus pomorum）；例えば、シトフィルスコクゾウムシ属種（Sitophilus spp.）の、グラナリーウィービル（Sitophilus granarius）、コクゾウムシ（Sitophilus zeamais）；その他の、イネゾウムシ（Echinocnemus squameus）、イモゾウムシ（Euscepes postfasciatus）、マツアナアキゾウムシ（Hylobius abietis）、アルファルファタコゾウムシ（Hypera postica）、イネミズゾウムシ（Lissohoptrus oryzophilus）、キンケクチブトゾウムシ（Otiorhynchus sulcatus）、アカアシチビコフキゾウムシ （Sitona lineatus）、シバオサゾウムシ（Sphenophorus venatus）；
（ｊ）コメツキムシ科（Elateridae）の、例えば、メラノツス属種（Melanotus spp.）の、マルクビクシコメツキ（Melanotus fortnumi）、カンシャクシコメツキ（Melanotus tamsuyensis）；
（ｋ）ケシキスイ科（Nitidulidae）の、例えば、ヒメヒラタケシキスイ（Epuraea domina）；
（ｌ）コガネムシ科（Scarabaeidae）の、例えば、アノマラ属種（Anomala spp.）の、ドウガネブイブイ（Anomala cuprea）、ヒメコガネ（Anomala rufocuprea）；その他の、キンイロハナムグリ（Cetonia aurata）、コアオハナムグリ（Gametis jucunda）、ナガチャコガネ（Heptophylla picea）、ヨーロッパコフキコガネ （Melolontha melolontha）、マメコガネ（Popillia japonica）；
（ｍ）キクイムシ科（Scolytidae）の、例えば、ヤツバキクイ （Ips typographus）；
（ｎ）ハネカクシ科（Staphylinidae）の、例えば、アオバアリガタハネカクシ（Paederus fuscipes）；
（ｏ）ゴミムシダマシ科（Tenebrionidae）の、例えば、チャイロコメノゴミムシダマシ（Tenebrio molitor）、コクヌストモドキ（Tribolium castaneum）；
（ｐ）コクヌスト科（Trogossitidae）の、例えば、コクヌスト（Tenebroides mauritanicus）。 (H) Ladybird family (Coccinellidae), for example, Epilachna spp., Epilachna varivestis, Epilachna vigintioctopunctata;
(i) Curculionidae, for example, Anthonomus spp., such as Anthonomus grandis and Anthonomus pomorum; for example, Sitophilus spp., such as Sitophilus granarius and Sitophilus zeamais; other species, such as Echinocnemus squameus, Euscepes postfasciatus, Hylobius abietis, Hypera postica, Lissohoptrus oryzophilus, Otiorhynchus sulcatus, and Otiorhynchus sulcatus. (Sitona lineatus), the grass weevil (Sphenophorus venatus);
(j) Elateridae, for example, Melanotus spp., Melanotus fortnumi, Melanotus tamsuyensis;
(K) Nitidulidae, for example, Epuraea domina;
(l) Scarabaeidae, for example, Anomala spp., Anomala cuprea, Anomala rufocuprea; other, Cetonia aurata, Gametis jucunda, Heptophylla picea, Melolontha melolontha, Popillia japonica;
(m) from the family Scolytidae, for example, Ips typographus;
(n) Staphylinidae, for example, Paederus fuscipes;
(O) Tenebrionidae, for example, Tenebrio molitor, Tribolium castaneum;
(p) Trogossitidae, for example, Tenebroides mauritanicus.
（５）ハエ目（Diptera）の害虫
（Ａ）ハエ亜目（Brachycera）
（ａ）ハモグリバエ科（Agromyzidae）の、例えば、リリオマイザ属種（Liriomyza spp.）の、ナスハモグリバエ（Liriomyza bryoniae）、ネギハモグリバエ（Liriomyza chinensis）、トマトハモグリバエ（Liriomyza sativae）、マメハモグリバエ（Liriomyza trifolii）；その他の、ナモグリバエ（Chromatomyia horticola）、イネハモグリバエ（Agromyza oryzae）；
（ｂ）ハナバエ科（Anthomyiidae）の、例えば、デリア属種（Delia spp.）の、タネバエ（Delia platura）、キャベツハナバエ （Delia radicum）；その他の、テンサイモグリハナバエ（Pegomya cunicularia）；
（ｃ）ショウジョウバエ科（Drosophilidae）の、例えば、ショウジョウバエ属種（Drosophila spp.）の、キイロショウジョウバエ（Drosophila melanogaster）、オウトウショウジョウバエ（Drosophila suzukii）；
（ｄ）ミギワバエ科（Ephydridae）の、例えば、イネヒメハモグリバエ（Hydrellia griseola）；
（ｅ）ハネオレバエ科（Psilidae）の、例えば、ニンジンサビバエ （Psila rosae）；
（ｆ）ミバエ科（Tephritidae）の、例えば、バクトロセラ属種（Bactrocera spp.）の、ウリミバエ（Bactrocera cucurbitae）、ミカンコミバエ（Bactrocera dorsalis）；例えば、ラゴレチス属種（Rhagoletis spp.）の、ヨーロッパオウトウミバエ （Rhagoletis cerasi）、リンゴミバエ （Rhagoletis pomonella）；その他の、チチュウカイミバエ（Ceratitis capitata）、オリーブミバエ（Dacus oleae）。 (5) Pests of the order Diptera (A) Suborder Brachycera
(a) Agromyzidae, for example, Liriomyza spp., Liriomyza bryoniae, Liriomyza chinensis, Liriomyza sativae, Liriomyza trifolii; others, Chromatomyia horticola, Agromyza oryzae;
(b) Anthomyiidae, for example, Delia spp., such as Delia platura and Delia radicum; and others, such as Pegomya cunicularia;
(C) Drosophilidae, for example, Drosophila spp., Drosophila melanogaster, Drosophila suzukii;
(D) Ephydridae, for example, Hydrellia griseola;
(e) from the family Psilidae, for example, the carrot fly (Psila rosae);
(F) Tephritidae, for example, Bactrocera spp., Bactrocera cucurbitae, Bactrocera dorsalis; Rhagoletis spp., Rhagoletis cerasi, Rhagoletis pomonella; and others, Ceratitis capitata, Dacus oleae.
（Ｂ）カ亜目（Nematocera）
（ａ）タマバエ科（Cecidomyiidae）の、例えば、ダイズサヤタマバエ（Asphondylia yushimai）、ソルガムタマバエ（Contarinia sorghicola）、ヘシアンバエ（Mayetiola destructor）、ムギアカタマバエ（Sitodiplosis mosellana）。 (B) Nematocera
(A) Cecidomyiidae, for example, Asphondylia yushimai, Contarinia sorghicola, Mayetiola destructor, and Sitodiplosis mosellana.
（６）バッタ目（Orthoptera）の害虫
（ａ）バッタ科（Acrididae）の、例えば、スキストセルカ属種（Schistocerca spp.）の、アメリカイナゴ （Schistocerca americana）、サバクトビバッタ （Schistocerca gregaria）；その他の、オーストラリアトビバッタ（Chortoicetes terminifera）、モロッコイナゴ （Dociostaurus maroccanus）、トノサマバッタ（Locusta migratoria）、ブラウンイナゴ（Locustana pardalina）、アカトビバッタ （Nomadacris septemfasciata）、コバネイナゴ（Oxya yezoensis）；
（ｂ）コオロギ科（Gryllidae）の、例えば、ヨーロッパイエコオロギ （Acheta domestica）、エンマコオロギ（Teleogryllus emma）；
（ｃ）ケラ科（Gryllotalpidae）の、例えば、ケラ（Gryllotalpa orientalis）；
（ｄ）キリギリス科（Tettigoniidae）の、例えば、クラズミウマ （Tachycines asynamorus）。 (6) Orthoptera pests (a) Acrididae, for example, Schistocerca spp., American locust (Schistocerca americana), desert locust (Schistocerca gregaria); other, Australian locust (Chortoicetes terminifera), Moroccan locust (Dociostaurus maroccanus), migratory locust (Locusta migratoria), brown locust (Locustana pardalina), red locust (Nomadacris septemfasciata), Oxya yezoensis;
(b) from the family Gryllidae, for example, the European house cricket (Acheta domestica), the field cricket (Teleogryllus emma);
(c) Gryllotalpidae, for example, Gryllotalpa orientalis;
(d) From the family Tettigoniidae, for example, Tachycines asynamorus.
　本発明の第２の実施形態の殺虫剤は、殺菌剤、殺虫・殺ダニ剤、殺線虫剤、殺土壌害虫剤などの他の有効成分；　植物調節剤、共力剤、肥料、土壌改良剤、動物用飼料などと混用または併用してもよい。
　本発明化合物と他の有効成分との組合せは、殺虫・殺ダニ・殺線虫活性に関して相乗効果が期待できる。相乗効果は、定法に従ってコルビーの式（Colby.S.R. ; Calculating Synergistic and Antagonistic Responses of Herbicide Combinations ; Weeds 15, 20-22頁, 1967）により確認することができる。
　本発明の殺虫剤と混用または併用することができる、殺虫・殺ダニ剤、殺線虫剤、殺土壌害虫剤などの具体例を以下に示す。下記の一覧は、IRACの殺虫剤作用機構分類表に準拠している。 The insecticide of the second embodiment of the present invention may be mixed or used in combination with other active ingredients such as fungicides, insecticides/acaricides, nematicides, and soil pesticides; plant regulators, synergists, fertilizers, soil conditioners, and animal feed.
The combination of the compound of the present invention and other active ingredients is expected to have a synergistic effect in terms of insecticidal, acaricidal and nematocidal activities. The synergistic effect can be confirmed by Colby's formula (Colby.SR; Calculating Synergistic and Antagonistic Responses of Herbicide Combinations; Weeds 15, 20-22, 1967) in accordance with a conventional method.
Specific examples of insecticides, acaricides, nematicides, soil pesticides, etc. that can be mixed or used in combination with the insecticide of the present invention are shown below. The following list is based on the IRAC insecticide mode of action classification table.
（１Ａ）アセチルコリンエステラーゼ（AChE）阻害剤（カーバメート系）
　アラニカルブ（Alanycarb）、アルジカルブ（Aldicarb）、ベンダイオカルブ（Bendiocarb）、ベンフラカルブ（Benfuracarb）、ブトカルボキシム（Butocarboxim）、 ブトキシカルボキシム（Butoxycarboxim）、カルバリル（Carbaryl）、カルボフラン（Carbofuran）、カルボスルファン（Carbosulfan）、エチオフェンカルブ（Ethiofencarb）、フェノブカルブ（Fenobucarb）、ホルメタネート（Formetanate）、フラチオカルブ（Furathiocarb）、イソプロカルブ（Isoprocarb）、メチオカルブ（Methiocarb）、メソミル（Methomyl）、メトルカルブ（Metolcarb）、オキサミル（Oxamyl）、ピリミカーブ（Pirimicarb）、プロポキスル（Propoxur）、チオジカルブ（Thiodicarb）、チオファノックス（Thiofanox）、トリアザメート（Triazamate）、トリメタカルブ（Trimethacarb）、ＸＭＣ、キシリルカルブ（Xylylcarb）；アルドキシカルブ（Aldoxycarb）、アリキシカルブ（Allyxycarb）、アミノカルブ（Aminocarb）、ブフェンカルブ（Bufencarb）、クロエトカルブ（Cloethocarb）、フェノチオカルブ（Fenothiocarb）、プロメカルブ（Promecarb）。 (1A) Acetylcholinesterase (AChE) inhibitors (carbamate type)
Alanycarb, Aldicarb, Bendiocarb, Benfuracarb, Butocarboxim, Butoxycarboxim, Carbaryl, Carbofuran, Carbosulfan, Ethiofencarb, Fenobucarb, Formetanate, Furathiocarb, Isoprocarb, Methiocarb, Methomyl, Metolcarb, Oxamyl, Piricarb micarb, Propoxur, Thiodicarb, Thiofanox, Triazamate, Trimethacarb, XMC, Xylylcarb; Aldoxycarb, Allyxycarb, Aminocarb, Bufencarb, Cloethocarb, Fenothiocarb, Promecarb.
（１Ｂ）アセチルコリンエステラーゼ（AChE）阻害剤（有機リン系）
　アセフェート（Acephate）、アザメチホス（Azamethiphos）、アジンホスエチル（Azinphos-ethyl）、アジンホスメチル（Azinphosmethyl）、カズサホス（Cadusafos）、クロレトキシホス（Chlorethoxyfos）、クロルフェンビンホス（Chlorfenvinphos）、クロルメホス（Chlormephos）、クロルピリホス（Chlorpyrifos）、クロルピリホスメチル（Chlorpyrifos-methyl）、クマホス（Coumaphos）、シアノホス（Cyanophos）、ジメトン-S-メチル（Demeton-S-methyl）、ダイアジノン（Diazinon）、ジクロルボス（Dichlorvos/ DDVP）、ジクロトホス（Dicrotophos）、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）、ファンフル（Famphur）、フェナミホス（Fenamiphos）、フェニトロチオン（Fenitrothion）、フェンチオン（Fenthion）、ホスチアゼート（Fosthiazate）、ヘプテノホス（Heptenophos）、イミシアホス（Imicyafos）、イソフェンホス（Isofenphos）、イソプロピル=O-(メトキシアミノチオホスホリル)サリチラート（Isopropyl O-(methoxyaminothio-phosphoryl) salicylate）、イソキサチオン（Isoxathion）、マラチオン（Malathion）、メカルバム（Mecarbam）、メタミドホス（Methamidophos）、メチダチオン（Methidathion）、メビンホス（Mevinphos）、モノクロトホス（Monocrotophos）、ナレッド（Naled）、オメトエート（Omethoate）、オキシジメトンメチル（Oxydemeton-methyl）、パラチオン（Parathion）、パラチオンメチル（Parathion-methyl）、フェントエート（Phenthoate）、ホレート（Phorate）、ホサロン（Phosalone）、ホスメット（Phosmet）、ホスファミドン（Phosphamidon）、ホキシム（Phoxim）、ピリミホスメチル（Pirimiphos- methyl）、プロフェノホス（Profenofos）、プロペタムホス（Propetamphos）、プロチオホス（Prothiofos）、ピラクロホス（Pyraclofos）、ピリダフェンチオン（Pyridaphenthion）、キナルホス（Quinalphos）、スルホテップ（Sulfotep）、テブピリムホス（Tebupirimfos）、テメホス（Temephos）、テルブホス（Terbufos）、テトラクロルビンホス（Tetrachlorvinphos）、チオメトン（Thiometon）、トリアゾホス（Triazophos）、トリクロルホン（Trichlorfon）、バミドチオン（Vamidothion）；ブロモホス－エチル（Bromophos-e）、シアノフェンホス（Cyanofenphos）、デメトン－Ｓ－メチルスルホン（Demeton-S-methylsulfone ）、ジアリホス（Dialifos）、ジクロフェンチオン（Dichlofenthion）、ジオキサベンゾホス（Dioxabenzofos）、エトリムホス（Etrimfos）、フェンスルホチオン（Fensulfothion）、ホノホス（Fonofos）、ホルモチオン（Formothion）、ヨードフェンホス（iodofenphos）、イサゾホス（Isazofos）、イソカルボホス（Isocarbofos）、メタクリホス（Methacrifos）、ホスホカルブ（Phosphocarb）、ピリミホス－エチル（Pirimiphos-e）、プロパホス（Propaphos）、プロトエート（Prothoate）、スルプロホス（Sulprofos）。 (1B) Acetylcholinesterase (AChE) inhibitors (organophosphorus)
Acephate, Azamethiphos, Azinphos-ethyl, Azinphosmethyl, Cadusafos, Chlorethoxyfos, Chlorfenvinphos, Chlormephos, Chlorpyrifos, Chlorpyrifos-methyl, Coumaphos, Cyanophos, Demeton-S-methyl, Diazinon, Dichlorvos DDVP), Dicrotophos, Dimethoate, Dimethylvinphos, Disulfoton, EPN, Ethion, Ethoprophos, Famphur, Fenamiphos, Fenitrothion, Fenthion, Fosthiazate, Heptenophos, Imicyafos, Isofenphos, Isopropyl O-(methoxyaminothio-phosphoryl) salicylate salicylate, Isoxathion, Malathion, Mecarbam, Methamidophos, Methidathion, Mevinphos, Monocrotophos, Naled, Omethoate, Oxydemeton-methyl, Parathion, Parathion-methyl, Phenthoate, Phorate, Phosalone, Phosmet, Phosphamidon, Phoxim, Pirimiphos-methyl methyl), profenofos, propetamphos, prothiofos, pyraclofos, pyridaphenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, trichlorfon, vamidothion; bromophos-e, cyanofenphos, demeton-S-methylsulfone ), Dialifos, Dichlofenthion, Dioxabenzofos, Etrimfos, Fensulfothion, Fonofos, Formothion, Iodofenphos, Isazofos, Isocarbofos, Methacrifos, Phosphocarb, Pirimiphos-ethyl, Propaphos, Prothoate, Sulprofos.
（２）GABA作動性塩化物イオン(塩素イオン)チャネルブロッカー
　クロルデン（Chlordane）、エンドスルファン（Endosulfan）；エチプロール（Ethiprole）、フィプロニル（Fipronil）；アセトプロール（Acetoprole）、カンフェクロル（Camphechlor）、ジエノクロル（Dienochlor）、ヘプタクロル（Heptachlor）、ピラフルプロール（Pyrafluprole）、ピリプロール（Pyriprole）；フルフィプロル（Flufiprole）。 (2) GABA-gated chloride ion (chloride ion) channel blockers: Chlordane, Endosulfan; Ethiprole, Fipronil; Acetoprole, Camphechlor, Dienochlor, Heptachlor, Pyrafluprole, Pyriprole; Flufiprole.
（３Ａ）ナトリウムチャネルモジュレーター（ピレスロイド系）
　アクリナトリン（Acrinathrin）、アレスリン（Allethrin）、d-シス-トランス-アレスリン（d-cis-trans Allethrin）、d-トランス-アレスリン（d-transAllethrin）、ビフェントリン（Bifenthrin）、ビオアレスリン（Bioallethrin）、ビオアレスリン-S-シクロペンテニル-異性体（Bioallethrin S-cyclopentenyl-isomer）、ビオレスメトリン（Bioresmethrin）、シクロプロトリン（Cycloprothrin）、シフルトリン（Cyfluthrin）、β-シフルトリン（beta-Cyfluthrin）、シハロトリン（Cyhalothrin）、λ-シハロトリン（lambda-Cyhalothrin）、γ-シハロトリン（gamma-Cyhalothrin）、シペルメトリン（Cypermethrin）、α-シペルメトリン（alpha-Cypermethrin）、β-シペルメトリン（beta-Cypermethrin）、θ-シペルメトリン（theta-Cypermethrin）、ζ-シペルメトリン（zeta-Cypermethrin）、シフェノトリン[(1R)-トランス異性体]（Cyphenothrin [(1R)-trans-isomers] ）、デルタメトリン（Deltamethrin）、エンペントリン[(EZ)-(1R)-異性体]（Empenthrin[(EZ)-(1R)-isomers] ）、エスフェンバレレート（Esfenvalerate）、エトフェンプロックス（Etofenprox）、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）、フルメトリン（Flumethrin）、τ-フルバリネート（tau-Fluvalinate）、ハルフェンプロックス（Halfenprox）、イミプロトリン（Imiprothrin）、カデスリン（Kadethrin）、ペルメトリン（Permethrin）、フェノトリン[(1R)-トランス異性体]（Phenothrin [(1R)-trans-isomer] ）、プラレトリン（Prallethrin）、ピレトリン（Pyrethrins）、レスメトリン（Resmethrin）、シラフルオフェン（Silafluofen）、テフルトリン（Tefluthrin）、テトラメスリン（Tetramethrin）、テトラメスリン[(1R)-異性体]（Tetramethrin[(1R)-isomers] ）、トラロメトリン（Tralomethrin）、トランスフルトリン（Transfluthrin）；κ-ビフェントリン（kappa-Bifenthrin）、ビオペルメトリン（Biopermethrin）、クロロプラレスリン（Chloroprallethrin）、ジメフルトリン（Dimefluthrin）、フェンフルトリン（Fenfluthrin）、フェンピリトリン（Fenpirithrin）、フルフェンプロックス（Flufenprox）、ヘプタフルスリン（Heptafluthrin）、メペルフルスリン（Meperfluthrin）、ε-メトフルトリン（epsilon-Metofluthrin）、モンフルオロトリン（Momfluorothrin）、ε-モンフルオロトリン（epsilon-Momfluorothrin）、トランス-ペルメトリン（trans-Permethrin）、プロフルトリン（Profluthrin）、プロトリフェンブト（Protrifenbute）、κ-テフルトリン（kappa-Tefluthrin）、テラレトリン（Terallethrin）、テトラメチルフルスリン（Tetramethylfluthrin）；ビオエタノメトリン（Bioethanomethrin）。
（３Ｂ）ナトリウムチャネルモジュレーター（ＤＤＴ類）
　ＤＤＴ、メトキシクロル（Methoxychlor）。 (3A) Sodium channel modulators (pyrethroids)
Acrinathrin, Allethrin, d-cis-trans Allethrin, d-transAllethrin, Bifenthrin, Bioallethrin, Bioallethrin-S-cyclopentenyl-isomer S-cyclopentenyl-isomer, Bioresmethrin, Cycloprothrin, Cyfluthrin, beta-Cyfluthrin, Cyhalothrin, lambda-Cyhalothrin, gamma-Cyhalothrin, Cypermethrin, alpha-Cypermethrin, beta-Cypermethrin, theta-Cypermethrin, zeta-Cypermethrin, Cyphenothrin [(1R)-trans-isomers] ), Deltamethrin, Empenthrin [(EZ)-(1R)-isomers], Esfenvalerate, Etofenprox, Fenpropathrin, Fenvalerate, Flucythrinate, Flumethrin, tau-Fluvalinate, Halfenprox, Imiprothrin, Kadethrin, Permethrin, Phenothrin [(1R)-trans-isomer] ), Prallethrin, Pyrethrins, Resmethrin, Silafluofen, Tefluthrin, Tetramethrin, Tetramethrin[(1R)-isomers], Tralomethrin, Transfluthrin; κ-Bifenthrin, Biopermethrin, Chloroprallethrin, Dimefluthrin, Fenfluthrin, Fenpirithrin, Flufenprox, Heptafluthrin, Meperfluthrin, ε-Metof Epsilon-Metofluthrin, Momfluorothrin, Epsilon-Momfluorothrin, Trans-Permethrin, Profluthrin, Protrifenbute, Kappa-Tefluthrin, Terallethrin, Tetramethylfluthrin; Bioethanomethrin.
(3B) Sodium channel modulators (DDTs)
DDT, methoxychlor.
（４）ニコチン性アセチルコリン受容体(nAChR)競合的モジュレーター
　アセタミプリド（Acetamiprid）、クロチアニジン（Clothianidin）、ジノテフラン（Dinotefuran）、イミダクロプリド（Imidacloprid）、ニテンピラム（Nitenpyram）、チアクロプリド（Thiacloprid）、チアメトキサム（Thiamethoxam）；ニコチン（Nicotine）；スルホキサフロル（Sulfoxaflor）；フルピラジフロン（Flupyradifurone）；トリフルメゾピリム（Triflumezopyrim）；ニチアジン（Nithiazine）、ジクロロメゾチアズ（Dicloromezotiaz）、フルピリミン（Flupyrimin）。
（５）ニコチン性アセチルコリン受容体(nAChR)アロステリックモジュレーター
　スピネトラム（Spinetoram）、スピノサド（Spinosad）。
（６）グルタミン酸作動性塩化物イオン(塩素イオン)チャネル(GluCl) アロステリックモジュレーター
　アバメクチン（Abamectin）、エマメクチン（Emamectin）、エマメクチン安息香酸塩（Emamectin-benzoate）、レピメクチン（Lepimectin）、ミルベメクチン（Milbemectin）；
　ドラメクチン（Doramectin）、エプリノメクチン（Eprinomectin）、イベルメクチン（Ivermectin）、モキシデクチン（Moxidectin）、セラメクチン（Selamectin）。 (4) Nicotinic acetylcholine receptor (nAChR) competitive modulators Acetamiprid, Clothianidin, Dinotefuran, Imidacloprid, Nitenpyram, Thiacloprid, Thiamethoxam; Nicotine; Sulfoxaflor; Flupyradifurone; Triflumezopyrim; Nithiazine, Dichloromezotiaz, Flupyrimin.
(5) Nicotinic acetylcholine receptor (nAChR) allosteric modulators: spinetoram, spinosad.
(6) Glutamate-gated chloride ion (chloride ion) channel (GluCl) allosteric modulators Abamectin, Emamectin, Emamectin-benzoate, Lepimectin, Milbemectin;
Doramectin, Eprinomectin, Ivermectin, Moxidectin, Selamectin.
（７）幼若ホルモン類似剤
　ヒドロプレン（Hydroprene）、キノプレン（Kinoprene）、メトプレン（Methoprene）；フェノキシカルブ（Fenoxycarb）；ピリプロキシフェン（Pyriproxifen）；ジオフェノラン（Diofenolan）、エポフェノナン（Epofenonane）、トリプレン（Triprene）。
（８）その他の非特異的(マルチサイト)阻害剤
　臭化メチル（Methyl bromide）、ハロゲン化アルキル類（alkyl halides）；クロルピクリン（Chloropicrin）；弗化アルミニウムナトリウム（Sodium aluminum fluoride）、フッ化スルフリル（Sulfuryl fluoride）；ホウ砂（Borax）、ホウ酸（Boric acid）、オクタホウ酸ニナトリウム塩（Disodium octaborate）、ホウ酸ナトリウム塩（Sodium borate）、メタホウ酸ナトリウム塩（Sodium metaborate）；吐酒石（Tartar emetic）；ダゾメット（Dazomet）、メタム（Metam）、メタムナトリウム塩（Metam Sodium）、メタムカリウム塩（Metam Potassium）。
（９）弦音器官TRPVチャネルモジュレーター
　ピメトロジン（Pymetrozine）、ピリフルキナゾン（Pyrifluquinazon）；アフィドピロペン（Afidopyropen）。
（１０）ダニ類成長阻害剤
　クロフェンテジン（Clofentezine）、ジフロビダジン（Diflovidazin）、ヘキシチアゾクス（Hexythiazox）；エトキサゾール（Etoxazole）。
（１１）微生物由来昆虫中腸内膜破壊剤
　B.t. subsp. israelensis、B.t. subsp. aizawai、B.t. subsp. kurstaki、B.t. subsp. tenebrionis；B.t.作物に含まれるタンパク質（B.t. crop proteins）：Cry1Ab、Cry1Ac、Cry1Fa、Cry1A.105、Cry2Ab、 Vip3A、mCry3A、Cry3Ab、Cry3Bb、Cry34Ab1/Cry35Ab1；Bacillus sphaericus。 (7) Juvenile hormone mimetics Hydroprene, Kinoprene, Methoprene; Fenoxycarb; Pyriproxifen; Diofenolan, Epophenonane, Triprene.
(8) Other non-specific (multi-site) inhibitors Methyl bromide, alkyl halides; Chloropicrin; Sodium aluminum fluoride, Sulfuryl fluoride; Borax, boric acid, disodium octaborate, sodium borate, sodium metaborate; Tartar emetic; Dazomet, Metam, Metam Sodium, Metam Potassium.
(9) Chordotonal Organ TRPV Channel Modulators Pymetrozine, Pyrifluquinazon; Afidopyropen.
(10) Mite growth inhibitors Clofentezine, Diflovidazin, Hexythiazox; Etoxazole.
(11) Microorganism-derived insect midgut membrane disrupting agents: Bt subsp. israelensis, Bt subsp. aizawai, Bt subsp. kurstaki, Bt subsp. tenebrionis; Bt crop proteins: Cry1Ab, Cry1Ac, Cry1Fa, Cry1A.105, Cry2Ab, Vip3A, mCry3A, Cry3Ab, Cry3Bb, Cry34Ab1/Cry35Ab1; Bacillus sphaericus.
（１２）ミトコンドリアATP合成酵素阻害剤
　ジアフェンチウロン（Diafenthiuron）；アゾシクロチン（Azocyclotin）、シヘキサチン（Cyhexatin）、酸化フェンブタスズ（Fenbutatin-oxide）；プロパルギット（Propargite）；テトラジホン（Tetradifon）。
（１３）プロトン勾配を撹乱する酸化的リン酸化脱共役剤
　クロルフェナピル（Chlorfenapyr）、ＤＮＯＣ（4,6-dinitro-o-cresol）、スルフルラミド（Sulfluramid）；ビナパクリル（Binapacryl）、ジノブトン（Dinobuton）、ジノカップ（Dinocap）。
（１４）ニコチン性アセチルコリン受容体(nAChR)チャネルブロッカー
　ベンスルタップ（Bensultap）、カルタップ塩酸塩（Cartap hydrochloride）、チオシクラム（Thiocyclam）、チオスルタップ－ナトリウム塩（Thiosultap-sodium）。 (12) Mitochondrial ATP synthase inhibitors Diafenthiuron; Azocyclotin, Cyhexatin, Fenbutatin-oxide; Propargite; Tetradifon.
(13) Oxidative phosphorylation uncouplers that disrupt the proton gradient Chlorfenapyr, DNOC (4,6-dinitro-o-cresol), Sulfluramid; Binapacryl, Dinobuton, Dinocap.
(14) Nicotinic acetylcholine receptor (nAChR) channel blockers Bensultap, Cartap hydrochloride, Thiosultap-sodium.
（１５）キチン生合成阻害剤、タイプ０
　ビストリフルロン（Bistrifluron）、クロルフルアズロン（Chlorfluazuron）、ジフルベンズロン（Diflubenzuron）、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）；フルアズロン（Fluazuron）。
（１６）キチン生合成阻害剤、タイプ１
　ブプロフェジン（Buprofezin）。
（１７）脱皮阻害剤
　シロマジン（Cyromazine）。
（１８）脱皮ホルモン(エクダイソン)受容体アゴニスト
　クロマフェノジド（Chromafenozide）、ハロフェノジド（Halofenozid）、メトキシフェノジド（Methoxyfenozide）、テブフェノジド（Tebufenozide）。 (15) Chitin biosynthesis inhibitor, type 0
Bistrifluron, Chlorfluazuron, Diflubenzuron, Flucycloxuron, Flufenoxuron, Hexaflumuron, Lufenuron, Novaluron, Noviflumuron, Teflubenzuron, Triflumuron; Fluazuron.
(16) Chitin biosynthesis inhibitor, type 1
Buprofezin.
(17) Molting inhibitor: Cyromazine.
(18) Molting hormone (ecdysone) receptor agonists Chromafenozide, halofenozide, methoxyfenozide, tebufenozide.
（１９）オクトパミン受容体アゴニスト
　アミトラズ（Amitraz）；クロルジメホルム（Chlordimeform）。
（２０）ミトコンドリア電子伝達系複合体III阻害剤（Qoサイト）
　ヒドラメチルノン（Hydramethylnon）；アセキノシル（Acequinocyl）；フルアクリピリム（Fluacrypyrim）；ビフェナゼート（Bifenazate）。
（２１）ミトコンドリア電子伝達系複合体Ｉ阻害剤(METI)
　フェナザキン（Fenazaquin）、フェンピロキシメート（Fenpyroximate）、ピリダベン（Pyridaben）、ピリミジフェン（Pyrimidifen）、テブフェンピラド（Tebufenpyrad）、トルフェンピラド（Tolfenpyrad）；ロテノン（Rotenone）。
（２２）電位依存性ナトリウムチャネルブロッカー
　インドキサカルブ（Indoxacarb）；メタフルミゾン（Metaflumizone）。
（２３）アセチルCoAカルボキシラーゼ阻害剤
　スピロジクロフェン（Spirodiclofen）、スピロメシフェン（Spiromesifen）、スピロピジオン（Spiropidion）、スピロテトラマト（Spirotetramat）。
（２４）ミトコンドリア電子伝達系複合体IV阻害剤
　リン化アルミニウム （Al-phosphide）、リン化カルシウム（Ca-phosphide）、リン化亜鉛（Zn-phosphide）、ホスフィン（Phosphine）；シアン化カルシウム（Ca-cyanide）シアン化ナトリウム（Na-cyanide）、シアン化カリウム（K-cyanide）。
（２５）ミトコンドリア電子伝達系複合体II阻害剤
　シエノピラフェン（Cyenopyrafen）、シフルメトフェン（Cyflumetofen）；ピフルブミド（Pyflubumide）。 (19) Octopamine receptor agonists Amitraz; Chlordimeform.
(20) Mitochondrial electron transport complex III inhibitor (Qo site)
Hydramethylnon; Acequinocyl; Fluacrypyrim; Bifenazate.
(21) Mitochondrial electron transport complex I inhibitor (METI)
Fenazaquin, Fenpyroximate, Pyridaben, Pyrimidifen, Tebufenpyrad, Tolfenpyrad; Rotenone.
(22) Voltage-dependent sodium channel blockers Indoxacarb; Metaflumizone.
(23) Acetyl-CoA carboxylase inhibitors Spirodiclofen, Spiromesifen, Spiropidione, Spirotetramat.
(24) Mitochondrial electron transport chain complex IV inhibitors Aluminum phosphide (Al-phosphide), calcium phosphide (Ca-phosphide), zinc phosphide (Zn-phosphide), phosphine (Phosphine); calcium cyanide (Ca-cyanide), sodium cyanide (Na-cyanide), potassium cyanide (K-cyanide).
(25) mitochondrial electron transport chain complex II inhibitors Cyenopyrafen, Cyflumetofen; Pyflubumide.
（２６）リアノジン受容体モジュレーター
　クロラントラニリプロール（Chlorantraniliprole）、シアントラニリプロール（Cyantraniliprole）、シクラニリプロール（Cyclaniliprole）、フルベンジアミド（Flubendiamide）、シハロジアミド（Cyhalodiamide）、テトラニリプロール（Tetraniliprole）；テトラクロラントラニリプロール（Tetrachlorantraniliprole）。
（２７）弦音器官ニコチンアミダーゼ阻害剤
　フロニカミド（Flonicamid）。
（２８）ＧＡＢＡ作動性塩化物イオン(塩素イオン)チャネルアロステリックモジュレーター
　ブロフラニリド（Broflanilide）、フルキサメタミド（Fluxametamide）、イソシクロセラム（Isocycloseram）；アフォキソラネル（Afoxolaner）、フルララネル（Fluralaner）、ロチラネル（Lotilaner）、サロラネル（Sarolaner）。 (26) Ryanodine receptor modulators Chlorantraniliprole, Cyantraniliprole, Cyclaniliprole, Flubendiamide, Cyhalodiamide, Tetraniliprole; Tetrachlorantraniliprole.
(27) Chordotonal organ nicotinamidase inhibitor Flonicamid.
(28) GABA-gated chloride ion (chloride ion) channel allosteric modulators Broflanilide, Fluxametamide, Isocycloseram; Afoxolaner, Fluralaner, Lotilaner, Sarolaner.
（２９）バキュロウイルス
顆粒病ウイルス類（Cydia pomonella GV、Thaumatotibia leucotreta GV）
核多角体病ウイルス（Anticarsia gemmatalis MNPV、Heliocoverpa armigera NPV）。
（３０）：ニコチン性アセチルコリン受容体 （nAChR）アロステリックモジュレーター-サイトII
GS-オメガ/カッパHXTX-Hv1aペプチド（GS-omega/kappa HXTX-Hv1a peptide）。
（３１）カルシウム活性化カリウムチャネル（KCa2）モジュレーター
アシノナピル（Acynonapyr）。
（３２）ミトコンドリア電子伝達系複合体III阻害剤（Qiサイト）
フロメトキン（Flometoquin）。
（３３）弦音器官モジュレーター（標的部位未特定）
ジンプロピリダズ （Dimpropyridaz）。 (29) Baculovirus granulosis viruses (Cydia pomonella GV, Thaumatotibia leucotreta GV)
Nuclear polyhedrosis viruses (Anticarsia gemmatalis MNPV, Heliocoverpa armigera NPV).
(30): Nicotinic acetylcholine receptor (nAChR) allosteric modulator - site II
GS-omega/kappa HXTX-Hv1a peptide.
(31) Calcium-activated potassium channel (KCa2) modulator Acynonapyr.
(32) Mitochondrial electron transport complex III inhibitor (Qi site)
Flometoquin.
(33) Chordotonal organ modulator (target site unspecified)
Dimpropyridaz.
（ＵＮ）作用機構不明の剤
　アザジラクチン（Azadirachtin）、ベンゾキシメート（Benzoximate）、ブロモプロピレート（Bromopropylate）、キノメチオナート（Chinomethionat）、ジコホル（Dicofol）、石灰硫黄合剤（Lime sulfur）、マンコゼブ（Mancozeb）、ピリダリル（Pyridalyl）、硫黄（Sulfur）。
（その他の殺虫剤、殺ダニ剤）
　アミドフルメット（Amidoflumet）、ベンゾメート（Benzomate）、ベンズピリモキサン（Benzpyrimoxan）、クロルベンジレート（Chlorobenzilate）、ジシクラニル（Dicyclanil）、フェノキサクリム（Fenoxacrim）、フェントリファニル（Fentrifanil）、フルベンジミン（Flubenzimine）、フルフェンジン（Flufenzine）、フルヘキサホン（Fluhexafon）、フルオピラム（Fluopyram）、メタフルミゾン（Metaflumizone）、メトキサジアゾン（Metoxadiazone）、オキサゾスルフィル（Oxazosulfyl）、テトラスル（Tetrasul）、トリアラセン（Triarathene）、チクロピラゾフロル（Tyclopyrazoflor）；ピペロニルブトキシド（Piperonyl butoxide）；クリオライト（Cryolite）、ベンクロチアズ（Benclothiaz）、1,3－ジクロロプロペン（1,3-Dichloropropene）、DCIP、フェニソブロモレート（Phenisobromolate）、メタアルデヒド（Metaldehyde）、クロチアゾベン（Clothiazoben）、ゴシップルア（Gossyplure）、ジャポニルア（Japonilure）、石油、オレイン酸ナトリウム、フルエンスルフォン（Fluensulfone）、トラロピリル（Tralopyril）、メチルネオデカンアミド（N-Methylneodecanamide）。 (UN) Agents with unknown mechanism of action: Azadirachtin, Benzoximate, Bromopropylate, Chinomethionat, Dicofol, Lime sulfur, Mancozeb, Pyridalyl, Sulfur.
(Other insecticides, acaricides)
Amidofulmet, Benzomate, Benzpyrimoxan, Chlorobenzilate, Dicyclanil, Fenoxacrim, Fentrifanil, Flubenzimine, Flufenzine, Fluhexafon, Fluopyram, Metaflumizone, Metoxadiazone, Oxazosulfyl, Tetrasul, Triarathene, Tyclopyrazoflor; Piperonyl Butoxide butoxide; Cryolite, Benclothiaz, 1,3-Dichloropropene, DCIP, Phenisobromolate, Metaldehyde, Clothiazobene, Gossyplure, Japonilure, Petroleum, Sodium Oleate, Fluensulfone, Tralopyril, N-Methylneodecanamide.
　本発明の殺虫剤と混用または併用することができる、駆虫剤の具体例を以下に示す。
（１）ベンズイミダゾール系：　フェンベンダゾール、アルベンダゾール、トリクラベンダゾール、オキシベンダゾール、メベンダゾール、オクスフェンダゾール、パーベンダゾール、フルベンダゾール、フェバンテル、ネトビミン、チオファネート、チアベンダゾール、カンベンダゾール。
（２）サリチルアニリド系：　クロサンテル、オキシクロザニド、ラフォキサニド、ニクロサミド。
（３）置換フェノール系：　ニトロキシニル、ニトロスカネイト。
（４）ピリミジン系：　ピランテル、モランテル。
（５）イミダゾチアゾール系：　レバミソール、テトラミソール。
（６）テトラヒドロピリミジン系：　プラジカンテル、エプシプランテル。
（７）その他の駆虫薬：　シクロジエン、リアニア、クロルスロン、メトロニダゾール、デミジトラズ、ピペラジン、ジエチルカルバマジン、ジクロロフェン、モネパンテル、トリベンジミジン、アミダンテル、チアセタルサミド、メラルソミン、アルセナマイド。 Specific examples of anthelmintics that can be mixed or used in combination with the insecticide of the present invention are shown below.
(1) Benzimidazoles: fenbendazole, albendazole, triclabendazole, oxibendazole, mebendazole, oxfendazole, perbendazole, flubendazole, febantel, netobimin, thiophanate, thiabendazole, and cambendazole.
(2) Salicylanilides: closantel, oxyclozanide, rafoxanide, niclosamide.
(3) Substituted phenols: nitroxynil, nitrosulfonate.
(4) Pyrimidines: pyrantel, morantel.
(5) Imidazothiazoles: levamisole, tetramisole.
(6) Tetrahydropyrimidines: praziquantel, epsiprantel.
(7) Other anthelmintics: cyclodiene, ryania, clorsulon, metronidazole, demiditraz, piperazine, diethylcarbamazine, dichlorophene, monepantel, tribendimidine, amidantel, thiacetarsamide, melarsomine, and arsenamide.
　本発明の殺虫剤と混用または併用することができる、殺菌剤の具体例を以下に示す。
（Ａ）核酸合成代謝阻害剤
（１）RNAポリメラーゼI阻害剤
　ベナラキシル、ベナラキシルM、フララキシル、メタラキシル、メタラキシルM；オキサジキシル；オフラセ。
（２）アデノシンデアミナーゼ阻害剤
　ブピリメート、ジメチリモール、エチリモール。
（３）ＤＮＡ／ＲＮＡ生合成阻害剤
　ヒメキサゾール、オクチリノン。
（４）ＤＮＡトポイソメラーゼ タイプII阻害剤
　オキソリニック酸。
（５）ＤＨＯＤＨ阻害剤
　イプフルフェノキン、キノフメリン。 Specific examples of fungicides that can be mixed or used in combination with the insecticide of the present invention are shown below.
(A) Nucleic acid synthesis metabolic inhibitors (1) RNA polymerase I inhibitors Benalaxyl, Benalaxyl M, Furalaxyl, Metalaxyl, Metalaxyl M; Oxadixyl; Ofurace.
(2) Adenosine deaminase inhibitors: bupirimate, dimethirimol, ethirimol.
(3) DNA/RNA biosynthesis inhibitors: hymexazole, octhilinone.
(4) DNA topoisomerase type II inhibitor oxolinic acid.
(5) DHODH inhibitors: ipflufenoquine, quinofumelin.
（Ｂ）細胞骨格とモーター蛋白質の阻害剤
（１）β-チューブリン重合阻害剤
　ベノミル、カルベンダジム、フベリダゾール、チアベンダゾール、チオファネート、チオファネートメチル、ジエトフェンカルブ、ゾキサミド、エタボキサム。
（２）その他の阻害剤
　ペンシクロン。フルオピコリド。フェナマクリル、メトラフェノン、ピリオフェノン、ピリダクロメチル。 (B) Inhibitors of cytoskeleton and motor proteins (1) β-tubulin polymerization inhibitors: benomyl, carbendazim, fuberidazole, thiabendazole, thiophanate, thiophanate-methyl, diethofencarb, zoxamide, ethaboxam.
(2) Other inhibitors: Pencycuron, fluopicolide, fenamacryl, metrafenone, pyriophenone, pyridaclomethyl.
（Ｃ）呼吸阻害剤
（１）複合体I： NADH酸化還元酵素の阻害剤
　ジフルメトリム、トルフェンピラド、フェナザキン。
（２）複合体II：コハク酸脱水素酵素の阻害剤
　ベノダニル、フルトラニル、メプロニル；イソフェタミド；フルオピラム；フェンフラム；カルボキシン、オキシカルボキシン；チフルザミド；ベンゾビンジフルピル、ビキサフェン、フルインダピル、フルキサピロキサド、フラメトピル、インピルフルキサム、イソピラザム、ペンフルフェン、ペンチオピラド、セダキサン；イソフルシプラム；ピジフルメトフェン；ボスカリド；ピラジフルミド。
（３）複合体III：チトクローム bc1（ユビキノール酸化酵素）Qo部位（cyt b遺伝子）の阻害剤
　アゾキシストロビン、クモキシストロビン、エノキサストロビン、フルフェノキシストロビン、ピコキシストロビン、ピラオキシストロビン；マンデストロビン ；ピラクロストロビン、ピラメトストロビン、トリクロピリカルブ；クレソキシムメチル、トリフロキシストロビン；ジモキシストロビン、フェナミンストロビン、メトミノストロビン、オリサストロビン；ファモキサドン；フルオキサストロビン；フェンアミドン；ピリベンカルブ；メチルテトラプロール。
（４）複合体III：ユビキノン還元酵素 Qi部位の阻害剤
　シアゾファミド；アミスルブロム；フェンピコキサミド、フロリルピコキサミド。
（５）酸化的リン酸化の脱共役剤
　ビナパクリル、ジノカップ、メプチルジノカップ；フルアジナム。
（６）酸化的リン酸化、ATP合成酵素の阻害剤
　酢酸トリフェニルスズ、塩化トリフェニルスズ、水酸化トリフェニルスズ。
（７）ATP輸送の阻害剤
　シルチオファム。
（８）複合体III：ユビキノン還元酵素（Qo部位、スチグマテリン結合サブサイト）の阻害剤
　アメトクトラジン。 (C) Respiratory inhibitors (1) Complex I: Inhibitors of NADH oxidoreductase: diflumetrim, tolfenpyrad, fenazaquin.
(2) Complex II: Inhibitors of succinate dehydrogenase Benodanil, flutolanil, mepronil; isofetamide; fluopyram; fenfuram; carboxin, oxycarboxin; thifluzamide; benzovindiflupyr, bixafen, fluindapyr, fluxapyroxad, furametpyr, impirfluxam, isopyrazam, penflufen, penthiopyrad, sedaxane; isoflucipram; pydiflumetofen; boscalid; pyraziflumid.
(3) Complex III: Inhibitors of cytochrome bc1 (ubiquinol oxidase) Qo site (cyt b gene): Azoxystrobin, cumoxystrobin, enoxastrobin, flufenoxystrobin, picoxystrobin, pyraoxystrobin; mandestrobin; pyraclostrobin, pyrametostrobin, triclopyricarb; kresoxim-methyl, trifloxystrobin; dimoxystrobin, phenaminestrobin, metominostrobin, orysastrobin; famoxadone; fluoxastrobin; fenamidone; pyribencarb; methyltetraprole.
(4) Complex III: Ubiquinone reductase Qi site inhibitors: cyazofamid; amisulbrom; fenpicoxamide, florylpicoxamide.
(5) Uncouplers of oxidative phosphorylation Binapacryl, dinocap, meptyldinocap; fluazinam.
(6) Inhibitors of oxidative phosphorylation and ATP synthase: triphenyltin acetate, triphenyltin chloride, triphenyltin hydroxide.
(7) ATP transport inhibitor: Silthiofam.
(8) Complex III: ubiquinone reductase (Qo site, stigmatellin-binding subsite) inhibitor ametoctrazine.
（Ｄ）アミノ酸および蛋白質合成阻害剤
　シプロジニル、メパニピリム、ピリメタニル；ブラストサイジンＳ、カスガマイシン、カスガマイシン塩酸塩、ストレプトマイシン、オキシテトラサイクリン。 (D) Amino acid and protein synthesis inhibitors: cyprodinil, mepanipyrim, pyrimethanil; blasticidin S, kasugamycin, kasugamycin hydrochloride, streptomycin, oxytetracycline.
（Ｅ）シグナル伝達阻害剤
　キノキシフェン、プロキナジド。フェンピクロニル、フルジオキソニル。クロゾリネート、ジメタクロン、イプロジオン、プロシミドン、ビンクロゾリン。 (E) Signal Transduction Inhibitors: Quinoxyfen, Proquinazid, Fenpiclonil, Fludioxonil, Chlozolinate, Dimethaclon, Iprodione, Procymidone, Vinclozolin.
（Ｆ）脂質生合成または輸送／細胞膜の構造または機能を阻害する剤
　エジフェンホス、イプロベンホス、ピラゾホス；イソプロチオラン。
　ビフェニル、クロロネブ、ジクロラン、キントゼン、テクナゼン、トルクロホスメチル；エトリジアゾール。ヨードカルブ、プロパモカルブ、プロパモカルブ塩酸塩、プロチオカルブ。ナタマイシン。オキサチアピプロリン、フルオキサピプロリン。 (F) Agents that inhibit lipid biosynthesis or transport/cell membrane structure or function: Edifenphos, iprobenfos, pyrazophos; isoprothiolane.
Biphenyl, chloroneb, dicloran, quintozene, tecnazene, tolclofos-methyl; etridiazole. iodocarb, propamocarb, propamocarb hydrochloride, prothiocarb. natamycin. oxathiapiproline, fluoxapiproline.
（Ｇ）細胞膜のステロール生合成（の阻害剤）
（１）ステロール生合成のC14位のデメチラーゼ（erg11/cyp51）の阻害剤
　トリホリン；ピリフェノックス、ピリソキサゾール；フェナリモル、ヌアリモール；イマザリル、オキスポコナゾール、ペフラゾエート、プロクロラズ、トリフルミゾール；アザコナゾール、ビテルタノール、ブロムコナゾール、シプロコナゾール、ジフェノコナゾール、ジニコナゾール、エポキシコナゾール、エタコナゾール、フェンブコナゾール、フルキンコナゾール、フルシラゾール、フルトリアホール、ヘキサコナゾール、イミベンコナゾール、イプコナゾール、メフェントリフルコナゾール、メトコナゾール、ミクロブタニル、ペンコナゾール、プロピコナゾール、シメコナゾール、テブコナゾール、テトラコナゾール、トリアジメホン、トリアジメノール、トリチコナゾール、プロチオコナゾール。
（２）ステロール生合成におけるΔ14還元酵素及びΔ８→Δ7-イソメラーゼ（erg24、erg2）の阻害剤
アルジモルフ、ドデモルフ、ドデモルフ酢酸塩、フェンプロピモルフ、トリデモルフ；フェンプロピジン、ピペラリン；スピロキサミン。
（３）ステロール生合成系のC4位脱メチル化における3-ケト還元酵素（erg27）の阻害剤
　フェンヘキサミド、フェンピラザミン。
（４）ステロール生合成系のスクワレンエポキシダーゼ（erg1）の阻害剤
　ピリブチカルブ、ナフチフィン、テルビナフィン。 (G) Inhibitors of sterol biosynthesis in cell membranes
(1) Inhibitors of C14 demethylase (erg11/cyp51) in sterol biosynthesis Triforine; pyrifenox, pyrisoxazole; fenarimol, nuarimol; imazalil, oxpoconazole, pefurazoate, prochloraz, triflumizole; azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imibenconazole, ipconazole, mefentrifluconazole, metconazole, myclobutanil, penconazole, propiconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triticonazole, prothioconazole.
(2) Inhibitors of Δ14 reductase and Δ8→Δ7-isomerase (erg24, erg2) in sterol biosynthesis: aldimorph, dodemorph, dodemorph acetate, fenpropimorph, tridemorph; fenpropidin, piperalin; spiroxamine.
(3) Inhibitors of 3-ketoreductase (erg27) in the C4 demethylation of sterol biosynthesis: fenhexamid and fenpyrazamine.
(4) Inhibitors of squalene epoxidase (erg1) in the sterol biosynthesis pathway: pyributicarb, naftifine, and terbinafine.
（Ｈ）細胞壁生合成の阻害剤
　ポリオキシン。ジメトモルフ、フルモルフ、ピリモルフ；ベンチアバリカルブ、イプロバリカルブ、バリフェナレート；マンジプロパミド。 (H) Inhibitors of cell wall biosynthesis Polyoxins: dimethomorph, flumorph, pyrimorph; benthiavalicarb, iprovalicarb, valifenalate; mandipropamid.
（Ｉ）細胞壁のメラニン合成の阻害剤
　フサライド；ピロキロン；トリシクラゾール。カルプロパミド、ジクロシメット、フェノキサニル。トルプロカルブ。 (I) Inhibitors of cell wall melanin synthesis: Fthalide; pyroquilon; tricyclazole. Carpropamid, diclocymet, fenoxanil. Tolprocarb.
（Ｊ）宿主植物の抵抗性誘導剤
　アシベンゾラルSメチル；プロベナゾール；チアジニル、イソチアニル。ラミナリン。オオイタドリ抽出液。バチルス・マイコイデス分離株J。ホセチル、亜リン酸および塩、ホセチルカルシウム、ホセチルナトリウム、ジクロベンチアゾクス。 (J) Resistance inducers in host plants: Acibenzolar-S-methyl; probenazole; tiadinil, isotianil. Laminarin. Polygonum persica extract. Bacillus mycoides isolate J. Fosetyl, phosphorous acid and salts, fosetyl calcium, fosetyl sodium, diclobenthiazox.
（Ｋ）作用機構不明の剤
　シモキサニル；テクロフタラム；トリアゾキシド；フルスルファミド；ジクロメジン；シフルフェナミド；ドジン、ドジン遊離塩基；フルチアニル；フェリムゾン；テブフロキン；ピカルブトラゾクス；バリダマイシン。
フルオピモミド、ピラプロポイン、アミノピリフェン、イプフェントリフルコナゾール、ジピメチトロン。 (K) Agents with unknown mechanism of action: cymoxanil; tecloftalam; triazoxide; flusulfamide; diclomedine; cyflufenamid; dodine, dodine free base; fluthianil; ferimzone; tebufloquine; picarbutrazox; validamycin.
Fluopimomide, pyrapropoin, aminopyrifen, ipfentrifluconazole, dipimethitron.
（Ｌ）多作用点接触活性を示す剤
　銅（種々の塩）、塩基性硫酸銅、ボルドー液、水酸化銅、銅ナフタレート、オキシ塩化銅、硫酸銅、酸化銅、オキシン銅；硫黄、石灰硫黄合剤；ファーバム、マンゼブ、マンネブ、メチラム、プロピネブ、チウラム、チアゾール亜鉛、ジネブ、ジラム；キャプタン、カプタホール、ホルペット；クロロタロニル；ジクロフルアニド、トリルフルアニド；グアザチン、グアザチン酢酸塩、イミノクタジン、イミノクタジン酢酸塩、イミノクタジンアルベシル酸塩；アニラジン；ジチアノン；キノメチオナート；フルオルイミド；メタスルホカルブ。 (L) Agents exhibiting multisite contact activity Copper (various salts), basic copper sulfate, Bordeaux mixture, copper hydroxide, copper naphthalate, copper oxychloride, copper sulfate, copper oxide, copper oxine; sulfur, lime sulfur mixture; ferbam, mancozeb, maneb, metiram, propineb, thiuram, zinc thiazole, zineb, ziram; captan, captafol, folpet; chlorothalonil; dichlofluanid, tolylfluanid; guazatine, guazatine acetate, iminoctadine, iminoctadine acetate, iminoctadine albesilate; anilazine; dithianone; quinomethionate; fluoroimide; metasulfocarb.
（Ｍ）その他の剤：
　DBEDC、フルオロフォルペット、グアザチンアセテート、ビス（8-キノリノラト）銅（II）、プロパミジン、クロロピクリン、シプロフラム、アグロバクテリウム、ベトキサジン、ジフェニルアミン、メチルイソチオシアネート（MITC）、ミルデオマイシン、カプサイシン、クフラネブ、シプロスルファミド、ダゾメット、デバカルブ、ジクロロフェン、ジフェンゾクワット、ジフェンゾクワットメチルスルホネート、フルメトベル、ホセチルカルシウム、ホセチルナトリウム、イルママイシン、ナタマイシン、ニトロタールイソプロピル、オキサモカルブ、プロパモシンナトリウム、ピロールニトリン、テブフロキン、トルニファニド、ザリラミド、アルゴフェーズ（Algophase）、アミカルチアゾール（Amicarthiazol）、オキサチアピプロリン（Oxathiapiprolin）、メチラム亜鉛、ベンチアゾール、トリクラミド、ユニコナゾール、ミルデオマイシン、オキシフェンチイン（Oxyfenthiin）、ピカルブトラゾクス（picarbutrazox）。 (M) Other agents:
DBEDC, Fluorofolpet, Guazatine acetate, Bis(8-quinolinolato)copper(II), Propamidine, Chloropicrin, Cyprofuram, Agrobacterium, Bethoxazin, Diphenylamine, Methylisothiocyanate (MITC), Mildeomycin, Capsaicin, Kufuraneb, Cyprosulfamide, Dazomet, Debacarb, Dichlorophen, Difenzoquat, Difenzoquat methylsulfonate, Flumetober, Fosetyl calcium, Fosetyl sodium, Irmamycin, Natamycin, Nitroisopropyl Nitrosulfate, Oxamocarb, Propamocin Sodium, Pyrrolnitrin, Tebufloquine, Tolnifanide, Zariramide, Algophase, Amicarthiazol, Oxathiapiprolin, Metiram Zinc, Benthiazole, Trichlamide, Uniconazole, Mildeomycin, Oxyfenthiin, Picarbutrazox.
　本発明の殺虫剤と混用または併用することができる、植物調節剤の具体例を以下に示す。
　１－メチルシクロプロペン、２，３，５－トリヨード安息香酸、ＩＡＡ、ＩＢＡ、ＭＣＰＡ、ＭＣＰＢ、４－ＣＰＡ、５－アミノレブリン酸塩酸塩、６－ベンジルアミノプリン、アブシシン酸、アビグリシン塩酸塩、アンシミドール、ブトルアリン、炭酸カルシウム、塩化カルシウム、ギ酸カルシウム、過酸化カルシウム、石灰硫黄、硫酸カルシウム、クロルメコートクロリド、クロロプロファム、塩化コリン、クロプロップ、シアナミド、シクラニリド、ダミノジッド、デシルアルコール、ジクロルプロップ、ジケグラック、ジメチピン、ジクワット、エテホン、エチクロゼート、フルメトラリン、フルルプリミドール、ホルクロルフェヌロン、ジベレリンＡ、ジベレリンＡ３、ヒメキサゾール、イナベンフィド、イソプロチオラン、カイネチン、マレイン酸ヒドラジド、メフルイジド、メピコートクロリド、酸化型グルタチオン、パクロブトラゾール、ペンディメタリン、プロヘキサジオンカルシウム、プロヒドロジャスモン、ピラフルフェンエチル、シントフェン、１－ナフタレン酢酸ナトリウム、シアン酸ナトリウム、ストレプトマイシン、チジアズロン、トリアペンテノール、トリブフォス、トリネキサパックエチル、ウニコナゾールＰ、１－ナフチルアセトアミド。 Specific examples of plant regulators that can be mixed or used in combination with the insecticide of the present invention are shown below.
1-Methylcyclopropene, 2,3,5-triiodobenzoic acid, IAA, IBA, MCPA, MCPB, 4-CPA, 5-aminolevulinic acid hydrochloride, 6-benzylaminopurine, abscisic acid, aviglycine hydrochloride, ancymidol, butruarin, calcium carbonate, calcium chloride, calcium formate, calcium peroxide, lime sulfur, calcium sulfate, chlormequat chloride, chlorpropham, choline chloride, cloprop, cyanamide, cyclanilide, daminozide, decyl alcohol, dichlorprop, dikeglac, dimethipine, diquat, ethephon, ethychlozate, flume Traline, flurprimidol, forchlorfenuron, gibberellin A, gibberellin A3, hymexazole, inabenfide, isoprothiolane, kinetin, maleic hydrazide, mefluidide, mepiquat chloride, oxidized glutathione, paclobutrazol, pendimethalin, prohexadione calcium, prohydrojasmone, pyraflufen-ethyl, synthofen, sodium 1-naphthaleneacetate, sodium cyanate, streptomycin, thidiazuron, triapentenol, tribufos, trinexapac-ethyl, uniconazole P, 1-naphthylacetamide.
〔製剤処方〕
　本発明の殺虫剤の製剤処方を示すが、添加物および添加割合は、これら実施例に限定されるべきではなく、広範囲に変化させることが可能である。製剤処方中の部は質量部を示し、％は質量％を示す。以下に農園芸用および水稲用の製剤処方を示す。
（製剤１：水和剤）
　本発明化合物４０部、珪藻土５３部、高級アルコール硫酸エステル４部、およびアルキルナフタレンスルホン酸塩３部を均一に混合して微細に粉砕して、有効成分４０％の水和剤を得る。
（製剤２：乳剤）
　本発明化合物３０部、キシレン３３部、ジメチルホルムアミド３０部、およびポリオキシエチレンアルキルアリルエーテル７部を混合溶解して、有効成分３０％の乳剤を得る。
（製剤３：粒剤）
　本発明化合物５部、タルク４０部、クレー３８部、ベントナイト１０部、およびアルキル硫酸ソーダ７部を均一に混合して微細に粉砕後、直径０．５～１．０ｍｍの粒状に造粒して有効成分５％の粒剤を得る。
（製剤４：粒剤）
　本発明化合物５部、クレー７３部、ベントナイト２０部、ジオクチルスルホサクシネートナトリウム塩１部、およびリン酸カリウム１部をよく粉砕混合し、水を加えてよく練り合せた後、造粒乾燥して有効成分５％の粒剤を得る。
（製剤５：懸濁剤）
　本発明化合物１０部、ポリオキシエチレンアルキルアリルエーテル４部、ポリカルボン酸ナトリウム塩２部、グリセリン１０部、キサンタンガム０．２部、および水７３．８部を混合し、粒度が３ミクロン以下になるまで湿式粉砕し、有効成分１０％の懸濁剤を得る。 [Formulation]
The formulations of the insecticide of the present invention are shown below, but the additives and the ratio of addition should not be limited to these examples and can be changed in a wide range. In the formulations, parts indicate parts by mass, and % indicates % by mass. The formulations for agricultural and horticultural use and for paddy rice are shown below.
(Formulation 1: Wettable powder)
40 parts of the compound of the present invention, 53 parts of diatomaceous earth, 4 parts of higher alcohol sulfate, and 3 parts of alkylnaphthalene sulfonate are uniformly mixed and finely ground to obtain a wettable powder containing 40% of the active ingredient.
(Formulation 2: Emulsion)
30 parts of the compound of the present invention, 33 parts of xylene, 30 parts of dimethylformamide, and 7 parts of polyoxyethylene alkyl allyl ether are mixed and dissolved to obtain an emulsifiable concentrate having an active ingredient content of 30%.
(Formulation 3: Granules)
5 parts of the compound of the present invention, 40 parts of talc, 38 parts of clay, 10 parts of bentonite, and 7 parts of sodium alkyl sulfate are uniformly mixed and finely ground, and then granulated into granules having a diameter of 0.5 to 1.0 mm to obtain granules containing 5% of the active ingredient.
(Formulation 4: Granules)
5 parts of the compound of the present invention, 73 parts of clay, 20 parts of bentonite, 1 part of dioctyl sulfosuccinate sodium salt, and 1 part of potassium phosphate are thoroughly ground and mixed, water is added, the mixture is thoroughly kneaded, and then granulated and dried to obtain granules containing 5% of the active ingredient.
(Formulation 5: Suspension)
10 parts of the compound of the present invention, 4 parts of polyoxyethylene alkyl allyl ether, 2 parts of sodium polycarboxylate, 10 parts of glycerin, 0.2 parts of xanthan gum, and 73.8 parts of water are mixed and wet-pulverized until the particle size becomes 3 microns or less, to obtain a suspension containing 10% of the active ingredient.
〔合成実施例〕
　次に、合成実施例を示し、本発明をより具体的に説明する。ただし、本発明は以下の合成実施例によって何ら制限されない。
　説明文中の略称は次の意味を示す。
　TEA：トリエチルアミン。DMF：N,N-ジメチルホルムアミド。THF：テトラヒドロフラン。DIPEA：ジイソプロピルエチルアミン。DMAP：4-ジメチルアミノピリジン。TMEDA：テトラメチルエチレンジアミン。Boc2O：二炭酸ジ-tert-ブチル。tBuXPhos：2-ジ-tert-ブチルホスフィノ-2’,4’,6’-トリイソプロピルビフェニル。Pd2(dba)3：トリス(ジベンジリデンアセトン)ジパラジウム(0)。Pd(PPh3)4：テトラキス(トリフェニルホスフィン)パラジウム(0)。 Synthesis Examples
Next, the present invention will be described in more detail with reference to synthesis examples, although the present invention is not limited to the following synthesis examples in any way.
The abbreviations in the description have the following meanings:
TEA: triethylamine. DMF: N,N-dimethylformamide. THF: tetrahydrofuran. DIPEA: diisopropylethylamine. DMAP: 4-dimethylaminopyridine. TMEDA: tetramethylethylenediamine. Boc2O: di-tert-butyl dicarbonate. tBuXPhos: 2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl. Pd2(dba)3: tris(dibenzylideneacetone)dipalladium(0). Pd(PPh3)4: tetrakis(triphenylphosphine)palladium(0).
（実施例１）
1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)phenyl)ureaの製造（化合物番号：A-1）
（工程１）
tert-butyl 〔1-[{(dimethylamino)methylene}amino]-1-oxopropan-2-yl〕carbamateの合成 Example 1
Preparation of 1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)phenyl)urea (Compound number: A-1)
(Step 1)
Synthesis of tert-butyl 〔1-[{(dimethylamino)methylene}amino]-1-oxopropan-2-yl〕carbamate
Figure JPOXMLDOC01-appb-C000007
Figure JPOXMLDOC01-appb-C000007
　tert-butyl (1-amino-1-oxopropan-2-yl)carbamate（１０．０ｇ）をジクロロメタン（１８０ｍｌ）に溶解させ、Ｎ，Ｎ－ジメチルホルムアミドジメチルアセタール（９．１ｍｌ）を加えて３時間加熱還流した。
　その後反応液を減圧留去し、目的化合物（１２．９ｇ）を得た。収率１００％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．４３（１Ｈ，ｓ），５．４８（１Ｈ，ｂｒ），４．３０（１Ｈ，ｔ），３．１２（３Ｈ，ｓ），３．０８（３Ｈ，ｓ），１．４３（９Ｈ，ｓ），１．３８（３Ｈ，ｄ）．
（工程２）
tert-butyl [1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethyl]carbamateの合成 tert-butyl(1-amino-1-oxopropan-2-yl)carbamate (10.0 g) was dissolved in dichloromethane (180 ml), and N,N-dimethylformamide dimethylacetal (9.1 ml) was added thereto, followed by heating under reflux for 3 hours.
The reaction mixture was then evaporated under reduced pressure to give the desired compound (12.9 g) in a 100% yield.
1H -NMR ( CDCl3 , δppm) 8.43 (1H,s), 5.48 (1H,br), 4.30 (1H,t), 3.12 (3H,s), 3.08 (3H,s), 1.43 (9H,s), 1.38 (3H,d).
(Step 2)
Synthesis of tert-butyl [1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethyl]carbamate
Figure JPOXMLDOC01-appb-C000008
Figure JPOXMLDOC01-appb-C000008
　tert-butyl 〔1-[{(dimethylamino)methylene}amino]-1-oxopropan-2-yl〕carbamate（１２．９ｇ）を１，４－ジオキサン（１８０ｍｌ）と酢酸（８９ｍｌ）に溶解させ、2-hydrazineylpyrimidine（７．０ｇ）を加えて６０℃で４時間撹拌した。
　その後反応液を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（１１．０ｇ）を得た。収率７１％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．８５（２Ｈ，ｄ），８．００（１Ｈ，ｓ），７．３４（１Ｈ，ｔ），６．００（１Ｈ，ｔ），５．５７（１Ｈ，ｄ），１．５５（３Ｈ，ｄ），１．４０（９Ｈ，ｓ）．
（工程３）
1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethan-1-amine dihydrochlorideの合成 tert-butyl [1-[{(dimethylamino)methylene}amino]-1-oxopropan-2-yl]carbamate (12.9 g) was dissolved in 1,4-dioxane (180 ml) and acetic acid (89 ml), and 2-hydrazineylpyrimidine (7.0 g) was added thereto and stirred at 60° C. for 4 hours.
The reaction mixture was then evaporated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (11.0 g) in a yield of 71%.
1H -NMR ( CDCl3 , δppm) 8.85 (2H,d), 8.00 (1H,s), 7.34 (1H,t), 6.00 (1H,t), 5.57 (1H,d), 1.55 (3H,d), 1.40 (9H,s).
(Step 3)
Synthesis of 1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethan-1-amine dihydrochloride
Figure JPOXMLDOC01-appb-C000009
Figure JPOXMLDOC01-appb-C000009
　tert-butyl [1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethyl]carbamate（１．６２ｇ）をジクロロメタン（３７ｍｌ）に溶解させ、４Ｍ塩酸１，４－ジオキサン溶液（７ｍｌ）を加え、室温で一晩撹拌した。
　その後反応液を減圧留去し、目的化合物（１．４２ｇ）を得た。収率１００％。
１Ｈ－ＮＭＲ　（ＣＤ３ＯＤ，δｐｐｍ）　８．９４（２Ｈ，ｄ），８．２１（１Ｈ，ｓ），７．５８（１Ｈ，ｔ），５．５１（１Ｈ，ｑ），１．７５（３Ｈ，ｄ）．
（工程４）
1-nitro-2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)benzeneの合成 tert-butyl[1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethyl]carbamate (1.62 g) was dissolved in dichloromethane (37 ml), and a 4M solution of hydrochloric acid in 1,4-dioxane (7 ml) was added thereto, followed by stirring at room temperature overnight.
The reaction mixture was then evaporated under reduced pressure to give the desired compound (1.42 g) in a 100% yield.
1H -NMR ( CD3OD , δppm) 8.94 (2H, d), 8.21 (1H, s), 7.58 (1H, t), 5.51 (1H, q), 1.75 (3H, d).
(Step 4)
Synthesis of 1-nitro-2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)benzene
Figure JPOXMLDOC01-appb-C000010
Figure JPOXMLDOC01-appb-C000010
　トリフルオロエタノール（０．６ｇ）をDMF（４ｍｌ）に溶解させ、０℃まで冷却した。その後水素化ナトリウム（０．２４ｇ）を加え０℃で３０分撹拌した。
　その後2-fluoro-1-nitro-4-(trifluoromethyl)benzene（０．８４ｇ）を加えてさらに室温で一晩撹拌した。
　その後反応液に水を加えて酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（１．２３ｇ）を得た。収率１００％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．００（１Ｈ，ｄ），７．５０（１Ｈ，ｄｄ），７．０９（１Ｈ，ｄ），４．５７（２Ｈ，ｑ）．
（工程５）
2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)anilineの合成 Trifluoroethanol (0.6 g) was dissolved in DMF (4 ml) and cooled to 0° C. Sodium hydride (0.24 g) was then added and the mixture was stirred at 0° C. for 30 minutes.
Thereafter, 2-fluoro-1-nitro-4-(trifluoromethyl)benzene (0.84 g) was added and the mixture was further stirred at room temperature overnight.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (1.23 g). Yield: 100%.
1 H-NMR (CDCl 3 , δ ppm) 8.00 (1H, d), 7.50 (1H, dd), 7.09 (1H, d), 4.57 (2H, q).
(Step 5)
Synthesis of 2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)aniline
Figure JPOXMLDOC01-appb-C000011
Figure JPOXMLDOC01-appb-C000011
　1-nitro-2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)benzene（１．２３ｇ）をエタノール（６ｍｌ）に溶解し、水（２ｍｌ）、鉄（１．１２ｇ）、塩化アンモニウム（１．０７ｇ）を順次加えて３時間加熱還流した。
　その後反応液をろ過して固形物を除去し、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（０．４１ｇ）を得た。収率４０％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　７．０８（１Ｈ，ｄｄ），６．９０（１Ｈ，ｄ），６．６８（１Ｈ，ｄ），４．３３（２Ｈ，ｑ），４．０８（２Ｈ，ｂｒ）．
（工程６）
1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)phenyl)ureaの合成 1-nitro-2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)benzene (1.23 g) was dissolved in ethanol (6 ml), and water (2 ml), iron (1.12 g), and ammonium chloride (1.07 g) were added successively, followed by heating under reflux for 3 hours.
The reaction solution was then filtered to remove solids, extracted with ethyl acetate, washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.41 g). Yield: 40%.
1H -NMR ( CDCl3 , δ ppm) 7.08 (1H, dd), 6.90 (1H, d), 6.68 (1H, d), 4.33 (2H, q), 4.08 (2H, br).
(Step 6)
Synthesis of 1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)phenyl)urea
Figure JPOXMLDOC01-appb-C000012
Figure JPOXMLDOC01-appb-C000012
　2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)aniline（０．２２ｇ）をTHF（４ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．３６ｍｌ）とトリホスゲン（０．１ｇ）を順次加えて０℃で３０分撹拌した。
　その後1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethan-1-aminedihydrochloride（０．２２ｇ）とTEA（０．３６ｍｌ）を加えてさらに室温で２時間撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた結晶をジエチルエーテルで洗浄することで目的化合物（０．３０ｇ）を得た。収率７５％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．９０（２Ｈ，ｄ），８．２４（１Ｈ，ｄ），８．０７（１Ｈ，ｓ），７．３４（１Ｈ，ｔ），７．３６（１Ｈ，ｂｒ），７．１３（２Ｈ，ｄ），６．９０（１Ｈ，ｂｒ），６．２９（１Ｈ，ｄｑ），４．４２－４．２８（２Ｈ，ｍ），１．６３（３Ｈ，ｄ）． 2-(2,2,2-trifluoroethoxy)-4-(trifluoromethyl)aniline (0.22 g) was dissolved in THF (4 ml) and cooled to 0° C. Then, TEA (0.36 ml) and triphosgene (0.1 g) were added in that order and stirred at 0° C. for 30 minutes.
Then, 1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethan-1-aminedihydrochloride (0.22 g) and TEA (0.36 ml) were added and the mixture was further stirred at room temperature for 2 hours.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting crystals were washed with diethyl ether to obtain the target compound (0.30 g). Yield: 75%.
1H -NMR ( CDCl3 , δ ppm) 8.90 (2H, d), 8.24 (1H, d), 8.07 (1H, s), 7.34 (1H, t), 7.36 (1H, br), 7.13 (2H, d), 6.90 (1H, br), 6.29 (1H, dq), 4.42-4.28 (2H, m), 1.63 (3H, d).
（実施例２）
1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)ureaの製造（化合物番号：B-1）
（工程１）
N-(6-(trifluoromethyl)pyridin-3-yl)pivalamideの合成 Example 2
Preparation of 1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)urea (Compound number: B-1)
(Step 1)
Synthesis of N-(6-(trifluoromethyl)pyridin-3-yl)pivalamide
Figure JPOXMLDOC01-appb-C000013
Figure JPOXMLDOC01-appb-C000013
　6-(trifluoromethyl)pyridin-3-amine（１７．６ｇ）をジクロロメタン（２７０ｍｌ）に溶解させ、DIPEA（２２．８ｍｌ）、DMAP（１．３３ｇ）、塩化ピバロイル（１４．７ｍｌ）を順次加えて室温で一晩撹拌した。
　その後反応液に飽和炭酸水素ナトリウム水溶液を加え、ジクロロメタンで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた結晶をジエチルエーテルで洗浄することで目的化合物（１３．９３ｇ）を得た。収率５２％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．６０（１Ｈ，ｄ），８．４４（１Ｈ，ｄｄ），７．６６（１Ｈ，ｄ），７．４９（１Ｈ，ｂｒ），１．３５（９Ｈ，ｓ）．
（工程２）
N-(4-iodo-6-(trifluoromethyl)pyridin-3-yl)pivalamideの合成 6-(trifluoromethyl)pyridin-3-amine (17.6 g) was dissolved in dichloromethane (270 ml), and DIPEA (22.8 ml), DMAP (1.33 g), and pivaloyl chloride (14.7 ml) were added successively, and the mixture was stirred at room temperature overnight.
The reaction mixture was then mixed with a saturated aqueous solution of sodium bicarbonate, extracted with dichloromethane, washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting crystals were washed with diethyl ether to obtain the target compound (13.93 g). Yield: 52%.
1H -NMR ( CDCl3 , δppm) 8.60 (1H, d), 8.44 (1H, dd), 7.66 (1H, d), 7.49 (1H, br), 1.35 (9H, s).
(Step 2)
Synthesis of N-(4-iodo-6-(trifluoromethyl)pyridin-3-yl)pivalamide
Figure JPOXMLDOC01-appb-C000014
Figure JPOXMLDOC01-appb-C000014
　N-(6-(trifluoromethyl)pyridin-3-yl)pivalamide（４．２６ｇ）をTHF（５８ｍｌ）に溶解させ、TMEDA（６．４ｍｌ）を加えて－７８℃まで冷却した。その後2.64M nBuLiヘキサン溶液（１６ｍｌ）を滴下し、さらに－７８℃で１時間撹拌した。
　その後ヨウ素（５．３ｇ）のTHF溶液（３５ｍｌ）を加えて０℃まで昇温し、さらに１時間撹拌した。
　その後反応液に飽和チオ硫酸ナトリウム水溶液を加えて酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（０．９７ｇ）を得た。収率１５％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．５４（１Ｈ，ｓ），８．０６（１Ｈ，ｓ），７．８４（１Ｈ，ｂｒ），１．３９（９Ｈ，ｓ）．
（工程３）
N-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)pivalamideの合成 N-(6-(trifluoromethyl)pyridin-3-yl)pivalamide (4.26 g) was dissolved in THF (58 ml), TMEDA (6.4 ml) was added, and the mixture was cooled to −78° C. Then, a 2.64 M nBuLi hexane solution (16 ml) was added dropwise, and the mixture was further stirred at −78° C. for 1 hour.
Thereafter, a solution of iodine (5.3 g) in THF (35 ml) was added, the temperature was raised to 0° C., and the mixture was further stirred for 1 hour.
Then, a saturated aqueous solution of sodium thiosulfate was added to the reaction solution, the solution was extracted with ethyl acetate, washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.97 g). Yield: 15%.
1H -NMR ( CDCl3 , δppm) 9.54 (1H,s), 8.06 (1H,s), 7.84 (1H,br), 1.39 (9H,s).
(Step 3)
Synthesis of N-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)pivalamide
Figure JPOXMLDOC01-appb-C000015
Figure JPOXMLDOC01-appb-C000015
　トリフルオロメタンスルフィン酸ナトリウム（０．５１ｇ）をアセトニトリル（１６ｍｌ）に溶解させ、塩化銅（Ｉ）（０．３２ｇ）を加えて０℃まで冷却した。その後トリフェニルホスフィン（１．７ｇ）を加えて室温で５時間撹拌した。
　その後反応液をろ過し、アセトニトリルで洗浄後ろ液を減圧留去し、これに1,3-ジメチル-2-イミダゾリジノン（１３ｍｌ）とN-(4-iodo-6-(trifluoromethyl)pyridin-3-yl)pivalamide（０．９７ｇ）を加えて１１０℃で一晩撹拌した。
　その後反応液にアンモニア水を加えて酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（０．７１ｇ）を得た。収率７９％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．９３（１Ｈ，ｓ），８．５５（１Ｈ，ｂｒ），７．９２（１Ｈ，ｓ），１．３７（９Ｈ，ｓ）
（工程４）
6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amineの合成 Sodium trifluoromethanesulfinate (0.51 g) was dissolved in acetonitrile (16 ml), copper(I) chloride (0.32 g) was added, and the mixture was cooled to 0° C. Then, triphenylphosphine (1.7 g) was added, and the mixture was stirred at room temperature for 5 hours.
The reaction mixture was then filtered, washed with acetonitrile, and the filtrate was evaporated under reduced pressure. 1,3-dimethyl-2-imidazolidinone (13 ml) and N-(4-iodo-6-(trifluoromethyl)pyridin-3-yl)pivalamide (0.97 g) were added thereto and stirred at 110° C. overnight.
Ammonia water was then added to the reaction solution, extracted with ethyl acetate, washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.71 g). Yield: 79%.
1H -NMR ( CDCl3 , δppm) 9.93 (1H,s), 8.55 (1H,br), 7.92 (1H,s), 1.37 (9H,s)
(Step 4)
Synthesis of 6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine
Figure JPOXMLDOC01-appb-C000016
Figure JPOXMLDOC01-appb-C000016
　N-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)pivalamide（０．５９ｇ）を濃硫酸（５．６ｍｌ）に溶解させ、１００℃で１時間撹拌した。
　その後反応液を飽和炭酸ナトリウム水溶液に加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、目的化合物（０．４４ｇ）を得た。収率１００％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．２７（１Ｈ，ｓ），７．７２（１Ｈ，ｓ），４．８９（２Ｈ，ｂｒ）．
（工程５）
1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)ureaの合成 N-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)pivalamide (0.59 g) was dissolved in concentrated sulfuric acid (5.6 ml) and stirred at 100° C. for 1 hour.
The reaction mixture was then added to a saturated aqueous solution of sodium carbonate, extracted with ethyl acetate, washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure to obtain the target compound (0.44 g). Yield: 100%.
1H -NMR ( CDCl3 , δppm) 8.27 (1H,s), 7.72 (1H,s), 4.89 (2H,br).
(Step 5)
Synthesis of 1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)urea
Figure JPOXMLDOC01-appb-C000017
Figure JPOXMLDOC01-appb-C000017
　6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine（０．１ｇ）をTHF（１．９ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．１６ｍｌ）とトリホスゲン（４５ｍｇ）を順次加えて０℃で３０分撹拌した。
　その後1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethan-1-amine dihydrochloride（０．１１ｇ）とTEA（０．１６ｍｌ）を加えてさらに室温で４時間撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（８２ｍｇ）を得た。収率４５％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．４９（１Ｈ，ｓ），８．９５（２Ｈ，ｄ），８．１２（１Ｈ，ｓ），８．０７（１Ｈ，ｂｒ），７．８１（１Ｈ，ｓ），７．７０（１Ｈ，ｓ），７．４５（１Ｈ，ｔ），６．３３（１Ｈ，ｄｑ），１．６８（３Ｈ，ｄ）． 6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine (0.1 g) was dissolved in THF (1.9 ml) and cooled to 0° C. Then, TEA (0.16 ml) and triphosgene (45 mg) were added in that order and stirred at 0° C. for 30 minutes.
Then, 1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethan-1-amine dihydrochloride (0.11 g) and TEA (0.16 ml) were added and the mixture was further stirred at room temperature for 4 hours.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (82 mg). Yield: 45%.
1H -NMR ( CDCl3 , δ ppm) 9.49 (1H, s), 8.95 (2H, d), 8.12 (1H, s), 8.07 (1H, br), 7.81 (1H, s), 7.70 (1H, s), 7.45 (1H, t), 6.33 (1H, dq), 1.68 (3H, d).
（実施例３）
1-(1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)ureaの製造（化合物番号：B-3）
（工程１）
5-fluoro-2-hydrazineylpyrimidineの合成 Example 3
Preparation of 1-(1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)urea (Compound number: B-3)
(Step 1)
Synthesis of 5-fluoro-2-hydrazineylpyrimidine
Figure JPOXMLDOC01-appb-C000018
Figure JPOXMLDOC01-appb-C000018
　2,5-difluoropyrimidine（３２．１ｇ）をエタノール（１６０ｍｌ）に溶解させ、ヒドラジン一水和物（２５．５ｇ）を加えて６０℃で５時間撹拌した。
　その後反応液をろ過し、水で洗浄した後ヘキサンで洗浄することで目的化合物（２５．２７ｇ）を得た。収率８２％。
１Ｈ－ＮＭＲ　（DMSO-ｄ６，δｐｐｍ）　８．４０（２Ｈ，ｄ），８．２０（１Ｈ，ｂｒ），４．１３（２Ｈ，ｂｒ）．
（工程２）
2-(1,3-dioxoisoindolin-2-yl)propanamideの合成 2,5-Difluoropyrimidine (32.1 g) was dissolved in ethanol (160 ml), and hydrazine monohydrate (25.5 g) was added thereto, followed by stirring at 60° C. for 5 hours.
The reaction solution was then filtered, washed with water and then with hexane to obtain the target compound (25.27 g) in a yield of 82%.
1H -NMR (DMSO- d6 , δ ppm) 8.40 (2H, d), 8.20 (1H, br), 4.13 (2H, br).
(Step 2)
Synthesis of 2-(1,3-dioxoisoindolin-2-yl)propanamide
Figure JPOXMLDOC01-appb-C000019
Figure JPOXMLDOC01-appb-C000019
　2-(1,3-dioxoisoindolin-2-yl)propanoic acid（４．３３ｇ）をジクロロメタン（６６ｍｌ）に溶解させ、塩化オキサリル（３．４ｍｌ）およびDMF触媒量を加えて室温で１時間撹拌した。
　その後反応液を減圧留去し、THF（６６ｍｌ）を加えて０℃まで冷却した。その後アンモニア水（３．６ｇ）を加えた後さらに室温で４時間撹拌した。
　反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、目的化合物（２．２ｇ）を得た。収率５１％。
１Ｈ－ＮＭＲ　（DMSO-ｄ６，δｐｐｍ）　７．９３－７．８３（４Ｈ，ｍ），７．５４（１Ｈ，ｂｒ），７．１６（１Ｈ，ｂｒ），４．６７（１Ｈ，ｑ），１．５３（３Ｈ，ｄ）．
（工程３）
2-(1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)isoindoline-1,3-dioneの合成 2-(1,3-dioxoisoindolin-2-yl)propanoic acid (4.33 g) was dissolved in dichloromethane (66 ml), and oxalyl chloride (3.4 ml) and a catalytic amount of DMF were added thereto, followed by stirring at room temperature for 1 hour.
The reaction solution was then evaporated under reduced pressure, THF (66 ml) was added, and the mixture was cooled to 0° C. Then, aqueous ammonia (3.6 g) was added, and the mixture was further stirred at room temperature for 4 hours.
Water was added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure to obtain the target compound (2.2 g). Yield: 51%.
1H -NMR (DMSO- d6 , δ ppm) 7.93-7.83 (4H, m), 7.54 (1H, br), 7.16 (1H, br), 4.67 (1H, q), 1.53 (3H, d).
(Step 3)
Synthesis of 2-(1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)isoindoline-1,3-dione
Figure JPOXMLDOC01-appb-C000020
Figure JPOXMLDOC01-appb-C000020
　2-(1,3-dioxoisoindolin-2-yl)propanamide（４．３２ｇ）をジクロロメタン（２４０ｍｌ）に溶解させ、Ｎ，Ｎ－ジメチルホルムアミドジメチルアセタール（１６．６ｍｌ）を加えて６時間加熱還流した。
　その後反応液を減圧留去し、これを１，４－ジオキサン（１９０ｍｌ）と酢酸（９７ｍｌ）に溶解させ、5-fluoro-2-hydrazineylpyrimidine（１４．８ｇ）を加えて５０℃で一晩撹拌した。
　その後反応液を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（１１．０ｇ）を得た。収率３２％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．６２（２Ｈ，ｓ），８．０８（１Ｈ，ｓ），７．８２（２Ｈ，ｄｄ），７．７１（２Ｈ，ｄｄ），６．３０（１Ｈ，ｑ），２．００（３Ｈ，ｄ）．
（工程４）
1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amineの合成 2-(1,3-dioxoisoindolin-2-yl)propanamide (4.32 g) was dissolved in dichloromethane (240 ml), and N,N-dimethylformamide dimethyl acetal (16.6 ml) was added thereto, followed by heating under reflux for 6 hours.
Thereafter, the reaction liquid was evaporated under reduced pressure, and the residue was dissolved in 1,4-dioxane (190 ml) and acetic acid (97 ml), and 5-fluoro-2-hydrazineylpyrimidine (14.8 g) was added thereto, followed by stirring at 50° C. overnight.
The reaction mixture was then evaporated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (11.0 g) in a yield of 32%.
1H -NMR ( CDCl3 , δ ppm) 8.62 (2H, s), 8.08 (1H, s), 7.82 (2H, dd), 7.71 (2H, dd), 6.30 (1H, q), 2.00 (3H, d).
(Step 4)
Synthesis of 1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine
Figure JPOXMLDOC01-appb-C000021
Figure JPOXMLDOC01-appb-C000021
　2-(1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)isoindoline-1,3-dione（２．０ｇ）をエタノール（２９ｍｌ）に溶解させ、ヒドラジン一水和物（０．４４ｇ）を加えて１時間加熱還流した。
　その後反応液をろ過、エタノールで洗浄し、ろ液を減圧留去してこれを次工程へ用いた。
（工程５）
1-(1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)ureaの合成 2-(1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)isoindoline-1,3-dione (2.0 g) was dissolved in ethanol (29 ml), and hydrazine monohydrate (0.44 g) was added thereto, followed by heating to reflux for 1 hour.
Thereafter, the reaction mixture was filtered and washed with ethanol, and the filtrate was evaporated under reduced pressure and used in the next step.
(Step 5)
Synthesis of 1-(1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)urea
Figure JPOXMLDOC01-appb-C000022
Figure JPOXMLDOC01-appb-C000022
　6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine（８０ｍｇ）をTHF（１．６ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．１３ｍｌ）とトリホスゲン（３６ｍｇ）を順次加えて０℃で３０分撹拌した。
　その後1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine（７５ｍｇ）とTEA（０．１３ｍｌ）を加えてさらに室温で２時間撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた結晶をジエチルエーテルで洗浄することで目的化合物（８０ｍｇ）を得た。収率５３％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．５１（１Ｈ，ｓ），８．８０（２Ｈ，ｓ），８．１０（１Ｈ，ｓ），７．７４（１Ｈ，ｓ），７．７０（１Ｈ，ｂｒ），７．６０（１Ｈ，ｂｒ），６．２０（１Ｈ，ｄｑ），１．６７（３Ｈ，ｄ）． 6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine (80 mg) was dissolved in THF (1.6 ml) and cooled to 0° C. Then, TEA (0.13 ml) and triphosgene (36 mg) were added in that order and stirred at 0° C. for 30 minutes.
Then, 1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine (75 mg) and TEA (0.13 ml) were added and the mixture was further stirred at room temperature for 2 hours.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting crystals were washed with diethyl ether to obtain the target compound (80 mg). Yield: 53%.
1H -NMR ( CDCl3 , δ ppm) 9.51 (1H, s), 8.80 (2H, s), 8.10 (1H, s), 7.74 (1H, s), 7.70 (1H, br), 7.60 (1H, br), 6.20 (1H, dq), 1.67 (3H, d).
（実施例４）
1-(1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)ureaの製造（化合物番号：B-5）
（工程１）
tert-butyl (1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamateの合成 Example 4
Preparation of 1-(1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)urea (Compound number: B-5)
(Step 1)
Synthesis of tert-butyl (1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate
Figure JPOXMLDOC01-appb-C000023
Figure JPOXMLDOC01-appb-C000023
　tert-butyl 〔1-[{(dimethylamino)methylene}amino]-1-oxopropan-2-yl〕carbamate（２．３ｇ）を１，４－ジオキサン（３１ｍｌ）と酢酸（１６ｍｌ）に溶解させ、5-fluoro-2-hydrazineylpyridine（１．４５ｇ）を加えて６０℃で４時間撹拌した。
　その後反応液を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（１．９ｇ）を得た。収率６６％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．３５（１Ｈ，ｄ），７．９３（１Ｈ，ｄｄ），７．９２（１Ｈ，ｓ），７．６１（１Ｈ，ｄｄｄ），５．８３（１Ｈ，ｄｑ），５．５８（１Ｈ，ｂｒ）１．５５（３Ｈ，ｄ），１．４１（９Ｈ，ｓ）．
（工程２）
1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine hydrochlorideの合成 tert-butyl [1-[{(dimethylamino)methylene}amino]-1-oxopropan-2-yl]carbamate (2.3 g) was dissolved in 1,4-dioxane (31 ml) and acetic acid (16 ml), and 5-fluoro-2-hydrazineylpyridine (1.45 g) was added thereto and stirred at 60° C. for 4 hours.
The reaction mixture was then evaporated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (1.9 g) in a yield of 66%.
1H -NMR ( CDCl3 , δ ppm) 8.35 (1H, d), 7.93 (1H, dd), 7.92 (1H, s), 7.61 (1H, ddd), 5.83 (1H, dq), 5.58 (1H, br) 1.55 (3H, d), 1.41 (9H, s).
(Step 2)
Synthesis of 1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine hydrochloride
Figure JPOXMLDOC01-appb-C000024
Figure JPOXMLDOC01-appb-C000024
　tert-butyl (1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate（１．９ｇ）をジクロロメタン（４０ｍｌ）に溶解させ、４Ｍ塩酸１，４－ジオキサン溶液（８ｍｌ）を加え、室温で一晩撹拌した。
　その後反応液を減圧留去して結晶として得た後、これを次工程へ用いた。
（工程３）
1-(1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)ureaの合成 tert-butyl (1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate (1.9 g) was dissolved in dichloromethane (40 ml), and a 4M solution of hydrochloric acid in 1,4-dioxane (8 ml) was added thereto, followed by stirring at room temperature overnight.
The reaction mixture was then evaporated under reduced pressure to give crystals which were then used in the next step.
(Step 3)
Synthesis of 1-(1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)urea
Figure JPOXMLDOC01-appb-C000025
Figure JPOXMLDOC01-appb-C000025
　6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine（０．１ｇ）をTHF（１．９ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．１６ｍｌ）とトリホスゲン（４５ｍｇ）を順次加えて０℃で３０分撹拌した。
　その後1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine hydrochloride（９３ｍｇ）とTEA（０．１６ｍｌ）を加えてさらに室温で４時間撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた結晶をヘキサンで洗浄することで目的化合物（０．１２ｇ）を得た。収率６３％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．３９（１Ｈ，ｓ），８．５４（１Ｈ，ｂｒ），８．４４（１Ｈ，ｄ），８．０４（１Ｈ，ｓ），８．０１（１Ｈ，ｄｄ），７．７８（１Ｈ，ｂｒ），７．７０（１Ｈ，ｄｄｄ），７．６６（１Ｈ，ｓ），６．１４（１Ｈ，ｄｑ），１．７２（３Ｈ，ｄ）． 6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine (0.1 g) was dissolved in THF (1.9 ml) and cooled to 0° C. Then, TEA (0.16 ml) and triphosgene (45 mg) were added in that order and stirred at 0° C. for 30 minutes.
Then, 1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine hydrochloride (93 mg) and TEA (0.16 ml) were added and the mixture was further stirred at room temperature for 4 hours.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting crystals were washed with hexane to obtain the target compound (0.12 g). Yield: 63%.
1H -NMR ( CDCl3 , δ ppm) 9.39 (1H, s), 8.54 (1H, br), 8.44 (1H, d), 8.04 (1H, s), 8.01 (1H, dd), 7.78 (1H, br), 7.70 (1H, ddd), 7.66 (1H, s), 6.14 (1H, dq), 1.72 (3H, d).
（実施例５）
1-(1-(1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)ureaの製造（化合物番号：B-7）
（工程１）
tert-butyl (1-(1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl) ethyl) carbamateの合成 Example 5
Preparation of 1-(1-(1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)urea (Compound number: B-7)
(Step 1)
Synthesis of tert-butyl (1-(1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl) ethyl) carbamate
Figure JPOXMLDOC01-appb-C000026
Figure JPOXMLDOC01-appb-C000026
　tert-butyl 〔1-[{(dimethylamino)methylene}amino]-1-oxopropan-2-yl〕carbamate（１８．５ｇ）を１，４－ジオキサン（２５０ｍｌ）と酢酸（１３０ｍｌ）に溶解させ、6-hydrazineylnicotinonitrile（１２．２ｇ）を加えて６０℃で４時間撹拌した。
　その後反応液を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（４．５２ｇ）を得た。収率１９％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．７９（１Ｈ，ｔ），８．１５－８．１０（２Ｈ，ｍ），７．９７（１Ｈ，ｓ），５．９６（１Ｈ，ｄｑ），５．５９（１Ｈ，ｄ），１．５６（３Ｈ，ｄ），１．４２（９Ｈ，ｓ）．
（工程２）
6-(5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl)nicotinonitrile hydrochlorideの合成 tert-butyl [1-[{(dimethylamino)methylene}amino]-1-oxopropan-2-yl]carbamate (18.5 g) was dissolved in 1,4-dioxane (250 ml) and acetic acid (130 ml), and 6-hydrazineylnicotinonitrile (12.2 g) was added thereto, followed by stirring at 60° C. for 4 hours.
The reaction mixture was then evaporated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (4.52 g) in a yield of 19%.
1H -NMR ( CDCl3 , δ ppm) 8.79 (1H, t), 8.15-8.10 (2H, m), 7.97 (1H, s), 5.96 (1H, dq), 5.59 (1H, d), 1.56 (3H, d), 1.42 (9H, s).
(Step 2)
Synthesis of 6-(5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl)nicotinonitrile hydrochloride
Figure JPOXMLDOC01-appb-C000027
Figure JPOXMLDOC01-appb-C000027
　tert-butyl (1-(1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl) ethyl) carbamate（１．９３ｇ）をジクロロメタン（４１ｍｌ）に溶解させ、４Ｍ塩酸１，４－ジオキサン溶液（８ｍｌ）を加え、室温で一晩撹拌した。
　その後反応液を減圧留去して結晶として得た後、これを次工程へ用いた。
（工程３）
1-(1-(1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)ureaの合成 tert-butyl (1-(1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl) ethyl) carbamate (1.93 g) was dissolved in dichloromethane (41 ml), and a 4M solution of hydrochloric acid in 1,4-dioxane (8 ml) was added thereto, followed by stirring at room temperature overnight.
The reaction mixture was then evaporated under reduced pressure to give crystals which were then used in the next step.
(Step 3)
Synthesis of 1-(1-(1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)urea
Figure JPOXMLDOC01-appb-C000028
Figure JPOXMLDOC01-appb-C000028
　6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine（０．１ｇ）をTHF（１．９ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．１６ｍｌ）とトリホスゲン（４５ｍｇ）を順次加えて０℃で３０分撹拌した。
　その後6-(5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl)nicotinonitrile hydrochloride（９６ｍｇ）とTEA（０．１６ｍｌ）を加えてさらに室温で４時間撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（０．１３ｇ）を得た。収率６７％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．４６（１Ｈ，ｓ），８．８８（１Ｈ，ｄｄ），８．２４－８．１７（２Ｈ，ｍ），８．０７（１Ｈ，ｓ），７．８０（１Ｈ，ｂｒ），７．７１（１Ｈ，ｓ），７．７７（１Ｈ，ｓ），６．２５（１Ｈ，ｄｑ），１．７１（３Ｈ，ｄ）． 6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine (0.1 g) was dissolved in THF (1.9 ml) and cooled to 0° C. Then, TEA (0.16 ml) and triphosgene (45 mg) were added in that order and stirred at 0° C. for 30 minutes.
Thereafter, 6-(5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl)nicotinonitrile hydrochloride (96 mg) and TEA (0.16 ml) were added and the mixture was further stirred at room temperature for 4 hours.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.13 g). Yield: 67%.
1H -NMR ( CDCl3 , δ ppm) 9.46 (1H, s), 8.88 (1H, dd), 8.24-8.17 (2H, m), 8.07 (1H, s), 7.80 (1H, br), 7.71 (1H, s), 7.77 (1H, s), 6.25 (1H, dq), 1.71 (3H, d).
（実施例６）
1-(1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)ureaの製造（化合物番号：B-9）
（工程１）
ethyl cyclopropanecarbimidate hydrochlorideの合成 Example 6
Preparation of 1-(1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)urea (Compound number: B-9)
(Step 1)
Synthesis of ethyl cyclopropanecarbimidate hydrochloride
Figure JPOXMLDOC01-appb-C000029
Figure JPOXMLDOC01-appb-C000029
　Cyclopropane carbonitrile（３．０ｇ）を４Ｍ塩酸１，４－ジオキサン溶液（３４ｍｌ）に溶解させ、０℃まで冷却した。その後エタノール（３．４ｍｌ）を加えて室温で一晩撹拌した。
　その後溶媒を減圧留去し、目的化合物（６．５３ｇ）を得た。収率９８％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　１２．２８（１Ｈ，ｂｒ），１１．２４（１Ｈ，ｂｒ），４．６０（２Ｈ，ｑ），２．４６－２．４０（１Ｈ，ｍ），１．４２（３Ｈ，ｔ），１．２８－１．１９（４Ｈ，ｍ）．
（工程２）
2-(1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)isoindoline-1,3-dioneの合成 Cyclopropane carbonitrile (3.0 g) was dissolved in a 4M solution of hydrochloric acid in 1,4-dioxane (34 ml) and cooled to 0° C. Then, ethanol (3.4 ml) was added and the mixture was stirred at room temperature overnight.
The solvent was then removed under reduced pressure to give the desired compound (6.53 g) in a 98% yield.
1H -NMR ( CDCl3 , δ ppm) 12.28 (1H, br), 11.24 (1H, br), 4.60 (2H, q), 2.46-2.40 (1H, m), 1.42 (3H, t), 1.28-1.19 (4H, m).
(Step 2)
Synthesis of 2-(1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)isoindoline-1,3-dione
Figure JPOXMLDOC01-appb-C000030
Figure JPOXMLDOC01-appb-C000030
　2-(1,3-dioxoisoindolin-2-yl)propanoic acid（５．４ｇ）をジクロロメタン（８２ｍｌ）に溶解させ、０℃まで冷却した。その後塩化オキサリル（４．２ｍｌ）とDMF触媒量を加えて室温で１時間撹拌した。その後溶媒を減圧留去し、酸塩化物を得た。
　続いて、ethyl cyclopropanecarbimidate hydrochloride（３．６９ｇ）をTHF（８２ｍｌ）に溶解させ、０℃まで冷却した。
　その後DIPEA（１７．２ｍｌ）と酸塩化物を順次加えて０℃で３０分撹拌し、続いて2-hydrazineylpyrimidine（３．０ｇ）を加えてさらに室温で一晩撹拌した。
　その後反応液に水を加えて酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（５．４３ｇ）を得た。収率６１％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．６９（２Ｈ，ｄ），７．７９（２Ｈ，ｄｄ），７．６８（２Ｈ，ｄｄ），７．１６（１Ｈ，ｔ），６．２５（１Ｈ，ｑ），２．２１－２．１４（１Ｈ，ｍ），１．９４（３Ｈ，ｄ），１．１３－０．９５（４Ｈ，ｍ）．
（工程３）
1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amineの合成 2-(1,3-dioxoisoindolin-2-yl)propanoic acid (5.4 g) was dissolved in dichloromethane (82 ml) and cooled to 0° C. Then, oxalyl chloride (4.2 ml) and a catalytic amount of DMF were added and stirred at room temperature for 1 hour. The solvent was then distilled off under reduced pressure to obtain the acid chloride.
Next, ethyl cyclopropanecarbimidate hydrochloride (3.69 g) was dissolved in THF (82 ml) and cooled to 0°C.
Then, DIPEA (17.2 ml) and the acid chloride were successively added, and the mixture was stirred at 0° C. for 30 minutes, and then 2-hydrazineylpyrimidine (3.0 g) was added, and the mixture was further stirred at room temperature overnight.
Water was then added to the reaction mixture, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (5.43 g). Yield: 61%.
1H -NMR ( CDCl3 , δ ppm) 8.69 (2H, d), 7.79 (2H, dd), 7.68 (2H, dd), 7.16 (1H, t), 6.25 (1H, q), 2.21-2.14 (1H, m), 1.94 (3H, d), 1.13-0.95 (4H, m).
(Step 3)
Synthesis of 1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine
Figure JPOXMLDOC01-appb-C000031
Figure JPOXMLDOC01-appb-C000031
　2-(1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)isoindoline-1,3-dione（１．４ｇ）をエタノール（１９ｍｌ）に溶解させ、ヒドラジン一水和物（０．２９ｇ）を加えて１時間加熱還流した。その後反応液をろ過、エタノールで洗浄し、ろ液を減圧留去してこれを次工程へ用いた。
（工程４）
1-(1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)ureaの合成 2-(1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)isoindoline-1,3-dione (1.4 g) was dissolved in ethanol (19 ml), hydrazine monohydrate (0.29 g) was added, and the mixture was heated under reflux for 1 hour. The reaction solution was then filtered and washed with ethanol, and the filtrate was evaporated under reduced pressure and used in the next step.
(Step 4)
Synthesis of 1-(1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-yl)urea
Figure JPOXMLDOC01-appb-C000032
Figure JPOXMLDOC01-appb-C000032
　6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine（０．１１ｇ）をTHF（２．１ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．１８ｍｌ）とトリホスゲン（０．１２ｇ）、DMAPを触媒量加え、室温で１時間撹拌した。
　その後反応液を減圧留去し、これをTHF（２．１ｍｌ）に懸濁させ、1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine（０．１３ｇ）とTEA（０．１２ｍｌ）を加えて室温で５時間撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（０．１５ｇ）を得た。収率６８％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．４３（１Ｈ，ｓ），８．９０（２Ｈ，ｄ），７．９９（１Ｈ，ｂｒ），７．７３（２Ｈ，ｓ），７．３９（１Ｈ，ｔ），６．３２（１Ｈ，ｄｑ），２．２０－２．１３（１Ｈ，ｍ），１．６６（３Ｈ，ｄ），１．１３－１．０１（４Ｈ，ｍ）． 6-(trifluoromethyl)-4-((trifluoromethyl)thio)pyridin-3-amine (0.11 g) was dissolved in THF (2.1 ml) and cooled to 0° C. Then, TEA (0.18 ml), triphosgene (0.12 g), and a catalytic amount of DMAP were added, and the mixture was stirred at room temperature for 1 hour.
The reaction liquid was then evaporated under reduced pressure, and the residue was suspended in THF (2.1 ml), 1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine (0.13 g) and TEA (0.12 ml) were added, and the mixture was stirred at room temperature for 5 hours.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.15 g). Yield: 68%.
1H -NMR ( CDCl3 , δ ppm) 9.43 (1H, s), 8.90 (2H, d), 7.99 (1H, br), 7.73 (2H, s), 7.39 (1H, t), 6.32 (1H, dq), 2.20-2.13 (1H, m), 1.66 (3H, d), 1.13-1.01 (4H, m).
（実施例７）
1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureaの製造（化合物番号：B-2）
（工程１）
tert-butyl (6-(trifluoromethyl)pyridin-3-yl)carbamateの合成 (Example 7)
Preparation of 1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea (Compound number: B-2)
(Step 1)
Synthesis of tert-butyl (6-(trifluoromethyl)pyridin-3-yl)carbamate
Figure JPOXMLDOC01-appb-C000033
Figure JPOXMLDOC01-appb-C000033
　6-(trifluoromethyl)pyridin-3-amine（１０．０ｇ）をジクロロメタン（１５０ｍｌ）に溶解させ、TEA（１０．３ｍｌ）とDMAP（０．７５ｇ）を加えて０℃まで冷却した。その後、Boc2O（１４．９ｍｌ）を加えて室温で一晩撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（９．４ｇ）を得た。収率５８％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．４７（１Ｈ，ｄ），８．２０（１Ｈ，ｄ），７．６２（１Ｈ，ｄ），６．７０（１Ｈ，ｂｒ），１．５４（９Ｈ，ｓ）．
（工程２）
tert-butyl (4-bromo-6-(trifluoromethyl)pyridin-3-yl)carbamateの合成 6-(trifluoromethyl)pyridin-3-amine (10.0 g) was dissolved in dichloromethane (150 ml), TEA (10.3 ml) and DMAP (0.75 g) were added, and the mixture was cooled to 0° C. Then, BocO (14.9 ml) was added, and the mixture was stirred at room temperature overnight.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (9.4 g). Yield: 58%.
1H -NMR ( CDCl3 , δppm) 8.47 (1H, d), 8.20 (1H, d), 7.62 (1H, d), 6.70 (1H, br), 1.54 (9H, s).
(Step 2)
Synthesis of tert-butyl (4-bromo-6-(trifluoromethyl)pyridin-3-yl)carbamate
Figure JPOXMLDOC01-appb-C000034
Figure JPOXMLDOC01-appb-C000034
　tert-butyl (6-(trifluoromethyl)pyridin-3-yl)carbamate（１０．８６ｇ）をTHF（１４０ｍｌ）に溶解させ、TMEDA（１５．４ｍｌ）を加えて－７８℃まで冷却した。その後2.64M nBuLiヘキサン溶液（３９ｍｌ）を滴下し、さらに－７８℃で１時間撹拌した。
　その後1,2-ジブロモエタン（８．８ｍｌ）を加えて室温まで昇温し、さらに５時間撹拌した。
　その後反応液に飽和塩化アンモニウム水溶液を加えて酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（８．１８ｇ）を得た。収率５８％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．４７（１Ｈ，ｓ），７．８２（１Ｈ，ｓ），７．０２（１Ｈ，ｂｒ），１．５６（９Ｈ，ｓ）
（工程３）
tert-butyl (4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)carbamateの合成 tert-butyl (6-(trifluoromethyl)pyridin-3-yl)carbamate (10.86 g) was dissolved in THF (140 ml), TMEDA (15.4 ml) was added, and the mixture was cooled to −78° C. Then, a 2.64 M nBuLi hexane solution (39 ml) was added dropwise, and the mixture was further stirred at −78° C. for 1 hour.
Then, 1,2-dibromoethane (8.8 ml) was added, the temperature was raised to room temperature, and the mixture was further stirred for 5 hours.
Then, a saturated aqueous solution of ammonium chloride was added to the reaction solution, extracted with ethyl acetate, washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (8.18 g). Yield: 58%.
1H -NMR ( CDCl3 , δppm) 9.47 (1H,s), 7.82 (1H,s), 7.02 (1H,br), 1.56 (9H,s)
(Step 3)
Synthesis of tert-butyl (4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)carbamate
Figure JPOXMLDOC01-appb-C000035
Figure JPOXMLDOC01-appb-C000035
　tert-butyl (4-bromo-6-(trifluoromethyl)pyridin-3-yl)carbamate（８．１８ｇ）をトルエン１２０ｍｌに溶解させ、トリフルオロエタノール（１２．０ｇ）、炭酸セシウム（１５．６ｇ）、tBuXPhos（０．６１ｇ）、Pd2(dba)3（０．６６ｇ）を順次加えて８０℃で６時間撹拌した。
　その後反応液に水を加えて酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（２．６２ｇ）を得た。収率３０％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．４４（１Ｈ，ｓ），７．１３（１Ｈ，ｓ），６．８５（１Ｈ，ｂｒ），４．５４（２Ｈ，ｑ），１．５６（９Ｈ，ｓ）．
（工程４）
4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amineの合成 tert-butyl (4-bromo-6-(trifluoromethyl)pyridin-3-yl)carbamate (8.18 g) was dissolved in 120 ml of toluene, and trifluoroethanol (12.0 g), cesium carbonate (15.6 g), tBuXPhos (0.61 g), and Pd2(dba)3 (0.66 g) were added in that order, and the mixture was stirred at 80°C for 6 hours.
Water was then added to the reaction mixture, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (2.62 g). Yield: 30%.
1H -NMR ( CDCl3 , δppm) 9.44 (1H,s), 7.13 (1H,s), 6.85 (1H,br), 4.54 (2H,q), 1.56 (9H,s).
(Step 4)
Synthesis of 4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine
Figure JPOXMLDOC01-appb-C000036
Figure JPOXMLDOC01-appb-C000036
　tert-butyl (4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)carbamate（２．６２ｇ）をジクロロメタン（３６ｍｌ）に溶解させ、０℃まで冷却した。その後トリフルオロ酢酸（２．８ｍｌ）を加えて室温で一晩撹拌した。
　その後反応液に飽和炭酸水素ナトリウム水溶液を加えてジクロロメタンで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（１．４０ｇ）を得た。収率７４％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．１１（１Ｈ，ｓ），７．０３（１Ｈ，ｓ），４．４９（２Ｈ，ｑ），４．１５（２Ｈ，ｂｒ），１．５６（９Ｈ，ｓ）
（工程５）
1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureaの合成 Tert-butyl (4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)carbamate (2.62 g) was dissolved in dichloromethane (36 ml) and cooled to 0° C. Then, trifluoroacetic acid (2.8 ml) was added and the mixture was stirred at room temperature overnight.
The reaction mixture was then added with a saturated aqueous solution of sodium bicarbonate, extracted with dichloromethane, washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (1.40 g). Yield: 74%.
1H -NMR ( CDCl3 , δppm) 8.11 (1H,s), 7.03 (1H,s), 4.49 (2H,q), 4.15 (2H,br), 1.56 (9H,s)
(Step 5)
Synthesis of 1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea
Figure JPOXMLDOC01-appb-C000037
Figure JPOXMLDOC01-appb-C000037
　4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine（８０ｍｇ）をTHF（１．５ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．１３ｍｌ）とトリホスゲン（３６ｍｇ）を加え、０℃で３０分撹拌した。
　その後1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethan-1-amine dihydrochloride（８１ｍｇ）とTEA（０．１３ｍｌ）を加えて室温で４時間撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた結晶をジエチルエーテルで洗浄することで目的化合物（３２ｍｇ）を得た。収率２２％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．４７（１Ｈ，ｓ），８．９３（２Ｈ，ｄ），８．０９（１Ｈ，ｓ），７．６８（１Ｈ，ｂｒ），７．４３（１Ｈ，ｔ），７．３４（１Ｈ，ｂｒ），６．８７（１Ｈ，ｓ），６．２９（１Ｈ，ｄｑ），４．５０－４．３１（２Ｈ，ｍ），１．６３（３Ｈ，ｄ）． 4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine (80 mg) was dissolved in THF (1.5 ml) and cooled to 0° C. Then, TEA (0.13 ml) and triphosgene (36 mg) were added, and the mixture was stirred at 0° C. for 30 minutes.
Then, 1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethan-1-amine dihydrochloride (81 mg) and TEA (0.13 ml) were added and stirred at room temperature for 4 hours.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting crystals were washed with diethyl ether to obtain the target compound (32 mg). Yield: 22%.
1H -NMR ( CDCl3 , δ ppm) 9.47 (1H, s), 8.93 (2H, d), 8.09 (1H, s), 7.68 (1H, br), 7.43 (1H, t), 7.34 (1H, br), 6.87 (1H, s), 6.29 (1H, dq), 4.50-4.31 (2H, m), 1.63 (3H, d).
（実施例８）
1-(1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureaの製造（化合物番号：B-4） (Example 8)
Preparation of 1-(1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea (Compound number: B-4)
Figure JPOXMLDOC01-appb-C000038
Figure JPOXMLDOC01-appb-C000038
　4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine（６５ｍｇ）をTHF（１．２ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．１ｍｌ）とトリホスゲン（３０ｍｇ）を加え、０℃で３０分撹拌した。
　その後1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine（６１ｍｇ）とTEA（０．１ｍｌ）を加えて室温で６時間撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた結晶をジエチルエーテルで洗浄することで目的化合物（２６ｍｇ）を得た。収率２１％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．４７（１Ｈ，ｓ），８．７８（２Ｈ，ｓ），８．０７（１Ｈ，ｓ），７．１４（１Ｈ，ｂｒ），７．００（１Ｈ，ｂｒ），６．９７（１Ｈ，ｓ），６．１７（１Ｈ，ｄｑ），４．５１－４．４０（２Ｈ，ｍ），１．６３（３Ｈ，ｄ）． 4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine (65 mg) was dissolved in THF (1.2 ml) and cooled to 0° C. Then, TEA (0.1 ml) and triphosgene (30 mg) were added, and the mixture was stirred at 0° C. for 30 minutes.
Then, 1-(1-(5-fluoropyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine (61 mg) and TEA (0.1 ml) were added and stirred at room temperature for 6 hours.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting crystals were washed with diethyl ether to obtain the target compound (26 mg). Yield: 21%.
1H -NMR ( CDCl3 , δ ppm) 9.47 (1H, s), 8.78 (2H, s), 8.07 (1H, s), 7.14 (1H, br), 7.00 (1H, br), 6.97 (1H, s), 6.17 (1H, dq), 4.51-4.40 (2H, m), 1.63 (3H, d).
（実施例９）
1-(1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureaの製造（化合物番号：B-6） Example 9
Preparation of 1-(1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea (Compound number: B-6)
Figure JPOXMLDOC01-appb-C000039
Figure JPOXMLDOC01-appb-C000039
　4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine（６５ｍｇ）をTHF（１．２ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．１ｍｌ）とトリホスゲン（３０ｍｇ）を順次加え、０℃で３０分撹拌した。
　その後1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine hydrochloride（６１ｍｇ）とTEA（０．１ｍｌ）を加えさらに室温で６時間撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた結晶をジエチルエーテルで洗浄することで目的化合物（６２ｍｇ）を得た。収率５１％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．４４（１Ｈ，ｓ），８．４２（１Ｈ，ｄ），８．００（１Ｈ，ｄｄ），７．９８（１Ｈ，ｓ），７．８２（１Ｈ，ｂｒ），７．６７（１Ｈ，ｄｄｄ），７．４３（１Ｈ，ｂｒ），６．８５（１Ｈ，ｂｒ），６．０９（１Ｈ，ｄｑ），４．４７－４．２９（２Ｈ，ｍ），１．６６（３Ｈ，ｄ）． 4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine (65 mg) was dissolved in THF (1.2 ml) and cooled to 0° C. Then, TEA (0.1 ml) and triphosgene (30 mg) were added in that order, and the mixture was stirred at 0° C. for 30 minutes.
Then, 1-(1-(5-fluoropyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine hydrochloride (61 mg) and TEA (0.1 ml) were added and the mixture was further stirred at room temperature for 6 hours.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting crystals were washed with diethyl ether to obtain the target compound (62 mg). Yield: 51%.
1H -NMR ( CDCl3 , δ ppm) 9.44 (1H, s), 8.42 (1H, d), 8.00 (1H, dd), 7.98 (1H, s), 7.82 (1H, br), 7.67 (1H, ddd), 7.43 (1H, br), 6.85 (1H, br), 6.09 (1H, dq), 4.47-4.29 (2H, m), 1.66 (3H, d).
（実施例１０）
1-(1-(1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureaの製造（化合物番号：B-8） Example 10
Preparation of 1-(1-(1-(5-cyanopyridin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea (Compound number: B-8)
Figure JPOXMLDOC01-appb-C000040
Figure JPOXMLDOC01-appb-C000040
　4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine（８０ｍｇ）をTHF（１．５ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．１３ｍｌ）とトリホスゲン（３６ｍｇ）を加え、０℃で３０分撹拌した。
　その後6-(5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl)nicotinonitrile hydrochloride（７７ｍｇ）とTEA（０．１３ｍｌ）を加えて室温で４時間撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた結晶をジエチルエーテルで洗浄することで目的化合物（７０ｍｇ）を得た。収率４５％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．４４（１Ｈ，ｓ），８．８７（１Ｈ，ｄｄ），８．２３－８．１８（２Ｈ，ｍ），８．０５（１Ｈ，ｓ），７．６１（１Ｈ，ｂｒ），７．２６（１Ｈ，ｂｒ），６．８５（１Ｈ，ｓ），６．２１（１Ｈ，ｄｑ），４．４７－４．２９（２Ｈ，ｍ），１．６７（３Ｈ，ｄ）． 4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine (80 mg) was dissolved in THF (1.5 ml) and cooled to 0° C. Then, TEA (0.13 ml) and triphosgene (36 mg) were added, and the mixture was stirred at 0° C. for 30 minutes.
Then, 6-(5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl)nicotinonitrile hydrochloride (77 mg) and TEA (0.13 ml) were added and stirred at room temperature for 4 hours.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting crystals were washed with diethyl ether to obtain the target compound (70 mg). Yield: 45%.
1H -NMR ( CDCl3 , δ ppm) 9.44 (1H, s), 8.87 (1H, dd), 8.23-8.18 (2H, m), 8.05 (1H, s), 7.61 (1H, br), 7.26 (1H, br), 6.85 (1H, s), 6.21 (1H, dq), 4.47-4.29 (2H, m), 1.67 (3H, d).
（実施例１１）
1-(1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureaの製造（化合物番号：B-10） (Example 11)
Preparation of 1-(1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea (Compound number: B-10)
Figure JPOXMLDOC01-appb-C000041
Figure JPOXMLDOC01-appb-C000041
　4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine（０．１ｇ）をTHF（２．０ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．１７ｍｌ）とトリホスゲン（４７ｍｇ）を加え、０℃で３０分撹拌した。
　その後1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine（０．１２ｇ）とTEA（０．１７ｍｌ）を加えて室温で４時間撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（０．１１ｇ）を得た。収率５３％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．４７（１Ｈ，ｓ），８．９０（２Ｈ，ｄ），８．３５（１Ｈ，ｂｒ），７．５１（１Ｈ，ｓ），７．３７（１Ｈ，ｔ），６．７８（１Ｈ，ｓ），６．２８（１Ｈ，ｄｑ），４．５６－４．２８（２Ｈ，ｍ），２．１５－２．０７（１Ｈ，ｍ），１．６１（３Ｈ，ｄ），１．１１－０．９５（４Ｈ，ｍ）． 4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine (0.1 g) was dissolved in THF (2.0 ml) and cooled to 0° C. Then, TEA (0.17 ml) and triphosgene (47 mg) were added, and the mixture was stirred at 0° C. for 30 minutes.
Then, 1-(3-cyclopropyl-1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine (0.12 g) and TEA (0.17 ml) were added and stirred at room temperature for 4 hours.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.11 g). Yield: 53%.
1H -NMR ( CDCl3 , δ ppm) 9.47 (1H, s), 8.90 (2H, d), 8.35 (1H, br), 7.51 (1H, s), 7.37 (1H, t), 6.78 (1H, s), 6.28 (1H, dq), 4.56-4.28 (2H, m), 2.15-2.07 (1H, m), 1.61 (3H, d), 1.11-0.95 (4H, m).
（実施例１２）
1-(1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureaの製造（化合物番号：B-11）
（工程１）
tert-butyl (1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamateの合成 Example 12
Preparation of 1-(1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea (Compound number: B-11)
(Step 1)
Synthesis of tert-butyl (1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate
Figure JPOXMLDOC01-appb-C000042
Figure JPOXMLDOC01-appb-C000042
　tert-butyl (1-(1-(6-chloropyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate（０．６５ｇ）をDMF（８．０ｍｌ）に溶解させ、シアン化亜鉛（０．７１ｇ）、Pd(PPh3)4（０．２３ｇ）を順次加えて窒素雰囲気下、８０℃で６時間撹拌した。
　その後反応液に水を加えて酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（０．５１ｇ）を得た。収率８１％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．２５（１Ｈ，ｄ），８．３２（１Ｈ，ｄ），８．０４（１Ｈ，ｓ），６．０５（１Ｈ，ｄｑ），５．５１（１Ｈ，ｄ），１．５９（３Ｈ，ｄ）．
（工程２）
1-(1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureaの合成 tert-butyl (1-(1-(6-chloropyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate (0.65 g) was dissolved in DMF (8.0 ml), and zinc cyanide (0.71 g) and Pd( PPh3 ) 4 (0.23 g) were added successively and stirred at 80°C for 6 hours under a nitrogen atmosphere.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.51 g). Yield: 81%.
1H -NMR ( CDCl3 , δ ppm) 9.25 (1H, d), 8.32 (1H, d), 8.04 (1H, s), 6.05 (1H, dq), 5.51 (1H, d), 1.59 (3H, d).
(Step 2)
Synthesis of 1-(1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea
Figure JPOXMLDOC01-appb-C000043
Figure JPOXMLDOC01-appb-C000043
　tert-butyl (1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate（０．４１ｇ）をジクロロメタン（１０ｍｌ）に溶解させ、０℃まで冷却した。その後トリフルオロ酢酸（１．５ｇ）を加えて室温で４時間撹拌した。
　その後反応液を減圧留去し、6-(5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl)pyrimidine-4-carbonitrileを得た。
　続いて、4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine（０．４４ｇ）をTHF（１０ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．２３ｍｌ）とトリホスゲン（０．２０ｇ）、DMAP触媒量を加え、０℃で３０分撹拌した。
　その後6-(5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl)pyrimidine-4-carbonitrileとTEA（０．７５ｍｌ）を加えて室温で４時間撹拌した。
　その後反応液を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（０．４７ｇ）を得た。収率７２％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．４５（１Ｈ，ｓ），９．３２（１Ｈ，ｓ），８．３７（１Ｈ，ｂｒ），８．０９（１Ｈ，ｂｒ），７．２８（２Ｈ，ｂｒ），６．９０（１Ｈ，ｂｒ），６．２８（１Ｈ，ｄｑ），４．４９－４．３６（２Ｈ，ｍ），１．６６（３Ｈ，ｄ）． tert-butyl (1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate (0.41 g) was dissolved in dichloromethane (10 ml) and cooled to 0° C. Then, trifluoroacetic acid (1.5 g) was added and the mixture was stirred at room temperature for 4 hours.
The reaction mixture was then evaporated under reduced pressure to give 6-(5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl)pyrimidine-4-carbonitrile.
Next, 4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine (0.44 g) was dissolved in THF (10 ml) and cooled to 0° C. Then, TEA (0.23 ml), triphosgene (0.20 g), and a catalytic amount of DMAP were added, and the mixture was stirred at 0° C. for 30 minutes.
Then, 6-(5-(1-aminoethyl)-1H-1,2,4-triazol-1-yl)pyrimidine-4-carbonitrile and TEA (0.75 ml) were added and stirred at room temperature for 4 hours.
The reaction mixture was then evaporated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.47 g) in a 72% yield.
1H -NMR ( CDCl3 , δ ppm) 9.45 (1H, s), 9.32 (1H, s), 8.37 (1H, br), 8.09 (1H, br), 7.28 (2H, br), 6.90 (1H, br), 6.28 (1H, dq), 4.49-4.36 (2H, m), 1.66 (3H, d).
（実施例１３）
6-(5-(1-(3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureido)ethyl)-1H-1,2,4-triazol-1-yl)pyrimidine-4-carboxamideの製造（化合物番号：B-12） (Example 13)
Preparation of 6-(5-(1-(3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureido)ethyl)-1H-1,2,4-triazol-1-yl)pyrimidine-4-carboxamide (Compound number: B-12)
Figure JPOXMLDOC01-appb-C000044
Figure JPOXMLDOC01-appb-C000044
　1-(1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea（０．２５ｇ）を１，４－ジオキサン（５ｍｌ）に溶解させ、４Ｍ塩酸１，４－ジオキサン溶液（２．０ｍｌ）、水３滴を加えて室温で一晩撹拌した。
　その後反応液を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（３１ｍｇ）を得た。収率１１％。
　液体クロマトグラフィー質量分析法(LCMS)における保持時間：１．１５分 1-(1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea (0.25 g) was dissolved in 1,4-dioxane (5 ml), and a 4M solution of hydrochloric acid in 1,4-dioxane (2.0 ml) and 3 drops of water were added thereto, followed by stirring at room temperature overnight.
The reaction mixture was then evaporated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (31 mg) in a yield of 11%.
Retention time in liquid chromatography mass spectrometry (LCMS): 1.15 min
（実施例１４）
6-(5-(1-(3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureido)ethyl)-1H-1,2,4-triazol-1-yl)pyrimidine-4-carbothioamideの製造（化合物番号：B-13） (Example 14)
Preparation of 6-(5-(1-(3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureido)ethyl)-1H-1,2,4-triazol-1-yl)pyrimidine-4-carbothioamide (Compound number: B-13)
Figure JPOXMLDOC01-appb-C000045
Figure JPOXMLDOC01-appb-C000045
　1-(1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea（０．１８ｇ）をDMF（５ｍｌ）に溶解させ、塩化マグネシウム六水和物（０．３６ｇ）、水硫化ナトリウム（０．１４）を順次加えて室温で一晩撹拌した。
　その後反応液に水を加えて酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（０．１７ｇ）を得た。収率８８％。
　液体クロマトグラフィー質量分析法(LCMS)における保持時間：１．３７分 1-(1-(1-(6-cyanopyrimidin-4-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea (0.18 g) was dissolved in DMF (5 ml), and magnesium chloride hexahydrate (0.36 g) and sodium hydrosulfide (0.14 g) were added successively and stirred at room temperature overnight.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.17 g). Yield: 88%.
Retention time in liquid chromatography mass spectrometry (LCMS): 1.37 min
（実施例１５）
1-(1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureaの製造（化合物番号：B-14）
（工程１）
2-chloro-5-(difluoro methoxy)pyrimidineの合成 (Example 15)
Preparation of 1-(1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea (Compound number: B-14)
(Step 1)
Synthesis of 2-chloro-5-(difluoro methoxy)pyrimidine
Figure JPOXMLDOC01-appb-C000046
Figure JPOXMLDOC01-appb-C000046
　2-chloropyrimidin-5-ol（１５．２７ｇ）をDMF（２３０ｍｌ）に溶解させ、クロロジフルオロ酢酸ナトリウム（４４．５ｇ）、炭酸カリウム（４０．４ｇ）、水（３９ｍｌ）を順次加えて９０℃で１時間撹拌した。
　その後反応液に水を加えて酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（１１．９３ｇ）を得た。収率５６％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．５３（２Ｈ，ｓ），６．６１（１Ｈ，ｔ）．
（工程２）
tert-butyl (1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamateの合成 2-Chloropyrimidin-5-ol (15.27 g) was dissolved in DMF (230 ml), and sodium chlorodifluoroacetate (44.5 g), potassium carbonate (40.4 g), and water (39 ml) were added successively, followed by stirring at 90° C. for 1 hour.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (11.93 g). Yield: 56%.
1 H-NMR (CDCl 3 , δ ppm) 8.53 (2H, s), 6.61 (1H, t).
(Step 2)
Synthesis of tert-butyl (1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)carbamate
Figure JPOXMLDOC01-appb-C000047
Figure JPOXMLDOC01-appb-C000047
　2-chloro-5-(difluoro methoxy)pyrimidine（２．０ｇ）をエタノール（３７ｍｌ）に溶解させヒドラジン一水和物（１．２ｇ）を加えて６０℃で３時間撹拌した。
　その後反応液に水を加えて酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。
　その後溶媒を減圧留去し、得られた濃縮物を１，４－ジオキサン（３０ｍｌ）と酢酸（１５ｍｌ）に溶解させ、tert-butyl 〔1-[{(dimethylamino)methylene}amino]-1-oxopropan-2-yl〕carbamate（２．１８ｇ）を加えて６０℃で４時間撹拌した。
　その後反応液を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（０．６４ｇ）を得た。収率２０％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．７３（２Ｈ，ｓ），８．０１（１Ｈ，ｓ），６．６６（１Ｈ，ｔ），５．９３（１Ｈ，ｄｑ），５．５２（１Ｈ，ｄ），１．５６（３Ｈ，ｄ），１．４２（９Ｈ，ｓ）．
（工程３）
1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine dihydrochlorideの合成 2-chloro-5-(difluoro methoxy)pyrimidine (2.0 g) was dissolved in ethanol (37 ml), and hydrazine monohydrate (1.2 g) was added thereto, followed by stirring at 60° C. for 3 hours.
Thereafter, water was added to the reaction mixture, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate.
The solvent was then removed under reduced pressure, and the resulting concentrate was dissolved in 1,4-dioxane (30 ml) and acetic acid (15 ml), and tert-butyl [1-[{(dimethylamino)methylene}amino]-1-oxopropan-2-yl]carbamate (2.18 g) was added thereto, followed by stirring at 60° C. for 4 hours.
The reaction mixture was then evaporated under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.64 g) in a yield of 20%.
1H -NMR ( CDCl3 , δppm) 8.73 (2H,s), 8.01 (1H,s), 6.66 (1H,t), 5.93 (1H,dq), 5.52 (1H,d), 1.56 (3H,d), 1.42 (9H,s).
(Step 3)
Synthesis of 1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine dihydrochloride
Figure JPOXMLDOC01-appb-C000048
Figure JPOXMLDOC01-appb-C000048
　tert-butyl (1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl) carbamate（０．６４ｇ）をジクロロメタン（１２ｍｌ）に溶解させ、４Ｍ塩酸１，４－ジオキサン溶液（２．２ｍｌ）を加え、室温で一晩撹拌した。
　その後反応液を減圧留去して結晶として得た後、これを次工程へ用いた。
（工程４）
1-(1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)ureaの合成 tert-butyl (1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl) carbamate (0.64 g) was dissolved in dichloromethane (12 ml), and 4M hydrochloric acid in 1,4-dioxane (2.2 ml) was added thereto, followed by stirring at room temperature overnight.
The reaction mixture was then evaporated under reduced pressure to give crystals which were then used in the next step.
(Step 4)
Synthesis of 1-(1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-yl)urea
Figure JPOXMLDOC01-appb-C000049
Figure JPOXMLDOC01-appb-C000049
　4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine（０．１ｇ）をTHF（２ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．１９ｍｌ）とトリホスゲン（４５ｍｇ）を加え、０℃で３０分撹拌した。
　その後1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine dihydrochloride（０．１３ｇ）を加えて室温で一晩撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物３９ｍｇを得た。収率１９％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　９．４８（１Ｈ，ｓ），８．７９（２Ｈ，ｓ），８．０７（１Ｈ，ｓ），７．２２（１Ｈ，ｂｒ），７．１２（１Ｈ，ｂｒ），６．９６（１Ｈ，ｓ），６．６９（１Ｈ，ｔ），６．２１（１Ｈ，ｄｑ），４．５１－４．３８（２Ｈ，ｍ），１．６４（３Ｈ，ｄ）． 4-(2,2,2-trifluoroethoxy)-6-(trifluoromethyl)pyridin-3-amine (0.1 g) was dissolved in THF (2 ml) and cooled to 0° C. Then, TEA (0.19 ml) and triphosgene (45 mg) were added, and the mixture was stirred at 0° C. for 30 minutes.
Then, 1-(1-(5-(difluoromethoxy)pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethan-1-amine dihydrochloride (0.13 g) was added and the mixture was stirred at room temperature overnight.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain 39 mg of the target compound. Yield: 19%.
1H -NMR ( CDCl3 , δ ppm) 9.48 (1H, s), 8.79 (2H, s), 8.07 (1H, s), 7.22 (1H, br), 7.12 (1H, br), 6.96 (1H, s), 6.69 (1H, t), 6.21 (1H, dq), 4.51-4.38 (2H, m), 1.64 (3H, d).
（実施例１６）
1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(2-(1,1,2,2-tetrafluoroethoxy)-4-(trifluoromethyl)phenyl)ureaの製造（化合物番号：A-2）
（工程１）
2-(1,1,2,2-tetrafluoroethoxy)-4-(trifluoromethyl)anilineの合成 (Example 16)
Preparation of 1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(2-(1,1,2,2-tetrafluoroethoxy)-4-(trifluoromethyl)phenyl)urea (Compound number: A-2)
(Step 1)
Synthesis of 2-(1,1,2,2-tetrafluoroethoxy)-4-(trifluoromethyl)aniline
Figure JPOXMLDOC01-appb-C000050
Figure JPOXMLDOC01-appb-C000050
　2-amino-5-(trifluoromethyl)phenol（０．５３ｇ）をDMF（５ｍｌ）に溶解させ、炭酸カリウム（０．６２ｇ）、1,1,2,2-tetrafluoro-1-iodoethane（１．０ｇ）を順次加えて６０℃で４時間撹拌した。
　その後反応液に水を加えて酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（０．７５ｇ）を得た。収率９０％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　７．３９（１Ｈ，ｓ），７．３２（１Ｈ，ｄｄ），６．６８２（１Ｈ，ｄ），５．９７（１Ｈ，ｔｔ），４．１３（２Ｈ，ｂｒ），１．５６（３Ｈ，ｄ），１．４２（９Ｈ，ｓ）．
（工程２）
1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(2-(1,1,2,2-tetrafluoroethoxy)-4-(trifluoromethyl)phenyl)ureaの合成 2-amino-5-(trifluoromethyl)phenol (0.53 g) was dissolved in DMF (5 ml), and potassium carbonate (0.62 g) and 1,1,2,2-tetrafluoro-1-iodoethane (1.0 g) were successively added thereto, followed by stirring at 60° C. for 4 hours.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.75 g). Yield: 90%.
1H -NMR ( CDCl3 , δppm) 7.39 (1H,s), 7.32 (1H,dd), 6.682 (1H,d), 5.97 (1H,tt), 4.13 (2H,br), 1.56 (3H,d), 1.42 (9H,s).
(Step 2)
Synthesis of 1-(1-(1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl)ethyl)-3-(2-(1,1,2,2-tetrafluoroethoxy)-4-(trifluoromethyl)phenyl)urea
Figure JPOXMLDOC01-appb-C000051
Figure JPOXMLDOC01-appb-C000051
　2-(1,1,2,2-tetrafluoroethoxy)-4-(trifluoromethyl)aniline（０．３２ｍｇ）をTHF（５ｍｌ）に溶解させ、０℃まで冷却した。その後TEA（０．６５ｍｌ）とトリホスゲン（０．１４ｇ）を加え、室温で１時間撹拌した。
　その後1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethan-1-amine dihydrochloride（０．１６ｇ）を加えて室温で一晩撹拌した。
　その後反応液に水を加え、酢酸エチルで抽出、飽和食塩水で洗浄し、有機層を無水硫酸マグネシウムで乾燥した。その後溶媒を減圧留去し、得られた濃縮物をシリカゲルカラムクロマトグラフィーで精製することで目的化合物（０．１４ｇ）を得た。収率４９％。
１Ｈ－ＮＭＲ　（ＣＤＣｌ３，δｐｐｍ）　８．９１（２Ｈ，ｄ），８．３７（１Ｈ，ｄ），８．０５（１Ｈ，ｓ），７．７０（１Ｈ，ｂｒ），７．４１（１Ｈ，ｔ），７．３５（１Ｈ，ｄ），７．２４（１Ｈ，ｂｒ），７．１２（１Ｈ，ｂｒ），６．２９（１Ｈ，ｄｑ），５．９０（１Ｈ，ｔ），１．６０（３Ｈ，ｄ）． 2-(1,1,2,2-tetrafluoroethoxy)-4-(trifluoromethyl)aniline (0.32 mg) was dissolved in THF (5 ml) and cooled to 0° C. Then, TEA (0.65 ml) and triphosgene (0.14 g) were added, and the mixture was stirred at room temperature for 1 hour.
Then, 1-{1-(pyrimidin-2-yl)-1H-1,2,4-triazol-5-yl}ethan-1-amine dihydrochloride (0.16 g) was added and the mixture was stirred at room temperature overnight.
Water was then added to the reaction solution, which was then extracted with ethyl acetate and washed with saturated saline, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was then distilled off under reduced pressure, and the resulting concentrate was purified by silica gel column chromatography to obtain the target compound (0.14 g). Yield: 49%.
1H -NMR ( CDCl3 , δ ppm) 8.91 (2H, d), 8.37 (1H, d), 8.05 (1H, s), 7.70 (1H, br), 7.41 (1H, t), 7.35 (1H, d), 7.24 (1H, br), 7.12 (1H, br), 6.29 (1H, dq), 5.90 (1H, t), 1.60 (3H, d).
　LCMS保持時間は、以下の方法で決定した。
　超高速高分離液体クロマトグラフ（ACQUITY UPLC H-Class：ウォーターズ社製）、ACQUITY UPLCフォトダイオードアレイ（ＰＤＡ）eλ検出器（ウォーターズ社製）及びACQUITY QDa 検出器(正及び負イオンエレクトロスプレーモードで、ＵＶ ＰＤＡ検出、ウォーターズ社製)を用いてなるシステムに、Waters CORTECS UPLC C18カラム（ウォーターズ社製、２．１×５０mm、１．６μm）を取り付け、温度４０℃、流量０．６mL/分、２μL注入で測定した。
　移動相(Ａ)に０．１%ギ酸を含む水を使用し、移動相(Ｂ)にアセトニトリルを使用した。移動相(Ｂ)の濃度を３０質量％で０．１５分間維持し、その後１．３５分間を掛けて移動相(Ｂ)の濃度を３０質量％から９５質量%に等速で上げ、０．５分間９５質量%で維持し、次いで移動相(Ｂ)の濃度を３０質量%にすぐ下げ、最後に移動相(Ｂ)の濃度を３０質量%で０．５０分間維持した。 LCMS retention times were determined in the following manner.
A Waters CORTECS UPLC C18 column (Waters, 2.1 x 50 mm, 1.6 μm) was attached to a system consisting of an ultra-high performance, high-resolution liquid chromatograph (ACQUITY UPLC H-Class: manufactured by Waters), an ACQUITY UPLC photodiode array (PDA) eλ detector (manufactured by Waters), and an ACQUITY QDa detector (positive and negative ion electrospray mode, UV PDA detection, manufactured by Waters), and measurements were performed at a temperature of 40°C, a flow rate of 0.6 mL/min, and 2 μL injection.
Water containing 0.1% formic acid was used as the mobile phase (A), and acetonitrile was used as the mobile phase (B). The concentration of the mobile phase (B) was maintained at 30% by mass for 0.15 minutes, then the concentration of the mobile phase (B) was increased from 30% by mass to 95% by mass at a constant rate over 1.35 minutes, maintained at 95% by mass for 0.5 minutes, then the concentration of the mobile phase (B) was immediately decreased to 30% by mass, and finally the concentration of the mobile phase (B) was maintained at 30% by mass for 0.50 minutes.
　合成実施例に挙げた化合物を含め、同様の製法で調製した化合物群を第１表に示す。第１表中には、化合物の物性として融点を併せて記した。 Table 1 shows a group of compounds prepared by the same method, including the compounds listed in the synthesis examples. Table 1 also lists the melting points as physical properties of the compounds.
Figure JPOXMLDOC01-appb-T000052
Figure JPOXMLDOC01-appb-T000052
Figure JPOXMLDOC01-appb-T000053
Figure JPOXMLDOC01-appb-T000053
Figure JPOXMLDOC01-appb-T000054
Figure JPOXMLDOC01-appb-T000054
Figure JPOXMLDOC01-appb-T000055
Figure JPOXMLDOC01-appb-T000055
Figure JPOXMLDOC01-appb-T000056
Figure JPOXMLDOC01-appb-T000056
Figure JPOXMLDOC01-appb-T000057
Figure JPOXMLDOC01-appb-T000057
Figure JPOXMLDOC01-appb-T000058
Figure JPOXMLDOC01-appb-T000058
〔生物試験〕
　本発明化合物が、殺虫剤の有効成分として有用であることを以下の試験例で示す。「部」は質量基準である。 [Biological Testing]
The usefulness of the compound of the present invention as an active ingredient of an insecticide will be demonstrated by the following test examples. "Parts" are by weight.
（殺虫率）
　殺虫率は、下記の式により計算した。
　　殺虫率（％）＝（死亡虫数／供試虫数）×１００ (Insecticidal rate)
The mortality rate was calculated according to the following formula:
Insect killing rate (%) = (number of dead insects/number of test insects) x 100
　本生物試験においては、本発明化合物に加え、特許文献１に記載の以下の化合物（以下、この化合物を対象化合物と呼ぶことがある。）についても試験を行った。 In this biological test, in addition to the compound of the present invention, the following compound described in Patent Document 1 (hereinafter, this compound may be referred to as the target compound) was also tested.
Figure JPOXMLDOC01-appb-C000059
Figure JPOXMLDOC01-appb-C000059
（試験用乳剤の調製）
　本発明化合物５部、ジメチルホルムアミド９３．６部、およびポリオキシエチレンアルキルアリールエーテル１．４部を混合溶解し、有効成分５％の乳剤(I)を調製した。
　対象化合物５部、ジメチルホルムアミド９３．６部、およびポリオキシエチレンアルキルアリールエーテル１．４部を混合溶解し、有効成分５％の乳剤(II)を調製した。 (Preparation of Test Emulsions)
5 parts of the compound of the present invention, 93.6 parts of dimethylformamide, and 1.4 parts of polyoxyethylene alkylaryl ether were mixed and dissolved to prepare an emulsifiable concentrate (I) having an active ingredient concentration of 5%.
5 parts of the target compound, 93.6 parts of dimethylformamide, and 1.4 parts of polyoxyethylene alkylaryl ether were mixed and dissolved to prepare an emulsifiable concentrate (II) having an active ingredient concentration of 5%.
（試験例１）アワヨトウに対する効力試験
　乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。希釈液(I)及び希釈液(II)にトウモロコシ葉片を３０秒間浸漬した。浸漬処理後のトウモロコシ葉片を、シャーレに入れ、アワヨトウ２齢幼虫５頭を放った。前記シャーレを、温度２５℃、湿度６０％の恒温室内に放置した。
　放虫から６日間経過したときに生死判定を行い、殺虫率を算出した。試験は２反復で行った。
　試験の結果を以下の第２表に示す。この表は、各化合物の表中に記載の濃度における殺虫率を示す。 (Test Example 1) Efficacy test against armyworm Emulsion (I) was diluted with water to a set concentration to obtain a dilution (I). Emulsion (II) was diluted with water to a set concentration to obtain a dilution (II). Corn leaf pieces were immersed in dilution (I) and dilution (II) for 30 seconds. The immersion-treated corn leaf pieces were placed in a petri dish, and five second-instar armyworm larvae were released into the dish. The petri dish was left in a thermostatic chamber at a temperature of 25°C and a humidity of 60%.
Six days after the release of the insects, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate.
The results of the test are shown in Table 2 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000060
Figure JPOXMLDOC01-appb-T000060
（試験例２）ハスモンヨトウに対する効力試験
　乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。希釈液(I)及び希釈液(II)のそれぞれにキャベツ葉を３０秒間浸漬した。浸漬処理後のキャベツ葉を風乾してシャーレに入れ、ハスモンヨトウ２齢幼虫５頭を放した。シャーレを温度２５℃、湿度６０％の恒温室内に放置した。
　放虫から６日間経過したときに生死判定を行い、殺虫率を算出した。試験は２反復で行った。
　試験の結果を以下の第３表に示す。この表は、各化合物の表中に記載の濃度における殺虫率を示す。 (Test Example 2) Efficacy test against Spodoptera litura Emulsion (I) was diluted with water to a set concentration to obtain a dilution (I). Emulsion (II) was diluted with water to a set concentration to obtain a dilution (II). Cabbage leaves were immersed in each of dilution (I) and dilution (II) for 30 seconds. After the immersion treatment, the cabbage leaves were air-dried and placed in a petri dish, into which five second-instar larvae of Spodoptera litura were released. The petri dish was left in a thermostatic chamber at a temperature of 25°C and a humidity of 60%.
Six days after the release of the insects, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate.
The results of the test are shown in Table 3 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000061
Figure JPOXMLDOC01-appb-T000061
Figure JPOXMLDOC01-appb-T000062
Figure JPOXMLDOC01-appb-T000062
（試験例３）コナガに対する効力試験
　乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。希釈液(I)及び希釈液(II)のそれぞれにキャベツ葉を前記希釈液中に３０秒間浸漬した。浸漬処理後のキャベツ葉を風乾してシャーレに入れ、コナガ２齢幼虫５頭を放した。シャーレを温度２５℃、湿度６０％の恒温室内に放置した。
　放虫から３日間経過したときに生死判定を行い、殺虫率を算出した。試験は２反復行った。
　試験の結果を以下の第４表に示す。この表は、各化合物の表中に記載の濃度における殺虫率を示す。 (Test Example 3) Efficacy test against diamondback moth Emulsion (I) was diluted with water to a set concentration to obtain dilution (I). Emulsion (II) was diluted with water to a set concentration to obtain dilution (II). Cabbage leaves were immersed in dilution (I) and dilution (II) for 30 seconds. After the immersion treatment, the cabbage leaves were air-dried and placed in a petri dish, into which five second-instar diamondback moth larvae were released. The petri dish was left in a thermostatic chamber at a temperature of 25°C and a humidity of 60%.
After 3 days from the release of the insects, the survival rate was determined and the mortality rate was calculated. The test was repeated twice.
The results of the test are shown in Table 4 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000063
Figure JPOXMLDOC01-appb-T000063
Figure JPOXMLDOC01-appb-T000064
Figure JPOXMLDOC01-appb-T000064
（試験例４）シロイチモジヨトウに対する効力試験
　乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。希釈液(I)及び希釈液(II)のそれぞれにキャベツ葉を３０秒間浸漬した。浸漬処理後のキャベツ葉を風乾してシャーレに入れ、シロイチモジヨトウ２齢幼虫５頭を放した。シャーレを温度２５℃、湿度６０％の恒温室内に放置した。
　放虫から６日間経過したときに生死判定を行い、殺虫率を算出した。試験は２反復で行った。
　試験の結果を以下の第５表に示す。この表は、各化合物の表中に記載の濃度における殺虫率を示す。 (Test Example 4) Efficacy test against beet armyworm Emulsion (I) was diluted with water to a set concentration to obtain a dilution (I). Emulsion (II) was diluted with water to a set concentration to obtain a dilution (II). Cabbage leaves were immersed in each of dilution (I) and dilution (II) for 30 seconds. After the immersion treatment, the cabbage leaves were air-dried and placed in a petri dish, into which five second-instar larvae of beet armyworm were released. The petri dish was left in a thermostatic chamber at a temperature of 25°C and a humidity of 60%.
Six days after the release of the insects, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate.
The results of the test are shown in Table 5 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000065
Figure JPOXMLDOC01-appb-T000065
Figure JPOXMLDOC01-appb-T000066
Figure JPOXMLDOC01-appb-T000066
（試験例５）チャノコカクモンハマキに対する効力試験
　乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。希釈液(I)及び希釈液(II)のそれぞれにお茶の葉を３０秒間浸漬した。浸漬処理後の茶葉を風乾してシャーレに入れ、チャノコカクモンハマキ２齢幼虫５頭を放した。シャーレを温度２５℃、湿度６０％の恒温室内に放置した。
　放虫から６日間経過したときに生死判定を行い、殺虫率を算出した。試験は２反復で行った。
　試験の結果を以下の第６表に示す。この表は、各化合物の表中に記載の濃度における殺虫率を示す。 (Test Example 5) Efficacy test against the smaller tea tortrix Emulsion (I) was diluted with water to a set concentration to obtain a dilution (I). Emulsion (II) was diluted with water to a set concentration to obtain a dilution (II). Tea leaves were immersed in each of dilution (I) and dilution (II) for 30 seconds. After the immersion treatment, the tea leaves were air-dried and placed in a petri dish, and five second-instar larvae of the smaller tea tortrix were released into the dish. The petri dish was left in a thermostatic chamber at a temperature of 25°C and a humidity of 60%.
Six days after the release of the insects, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate.
The results of the test are shown in Table 6 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000067
Figure JPOXMLDOC01-appb-T000067
（試験例６）ワタアブラムシに対する効力試験
　３寸鉢にキュウリを播種した。発芽から１０日間経過したキュウリに、ワタアブラムシ雌成虫を放した。翌日に、産下された１齢若虫を残し、雌成虫を除去した。
　乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。希釈液(I)及び希釈液(II)を前記のキュウリに散布した。その後、キュウリを、温度２５℃、湿度６０％の恒温室内で保管した。
　６日間経過したときに生死判定を行い、殺虫率を算出した。試験は２反復で行った。
　試験の結果を以下の第７表に示す。この表は、各化合物の表中に記載の濃度における殺虫率を示す。 (Test Example 6) Efficacy test against cotton aphid Cucumbers were sown in 3-inch pots. Female cotton aphid adults were released on the cucumbers 10 days after germination. The next day, the female adults were removed, leaving only the first-instar nymphs that had been laid.
Emulsion (I) was diluted with water to a set concentration to obtain a diluted solution (I). Emulsion (II) was diluted with water to a set concentration to obtain a diluted solution (II). The diluted solutions (I) and (II) were sprayed on the cucumbers. The cucumbers were then stored in a constant temperature room at a temperature of 25°C and a humidity of 60%.
After 6 days, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate.
The results of the test are shown in Table 7 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000068
Figure JPOXMLDOC01-appb-T000068
（試験例７）モモアカアブラムシに対する効力試験
　３寸鉢にチンゲンサイ(第７本葉展開期)にモモアカアブラムシ雌成虫を放した。翌日に、産下された１齢若虫を残し、雌成虫を除去した。
　乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。希釈液(I)及び希釈液(II)を前記のチンゲンサイに散布した。その後、チンゲンサイを、温度２５℃、湿度６０％の恒温室内で保管した。
　６日間経過したときに生死判定を行い、殺虫率を算出した。試験は２反復で行った。
　試験の結果を以下の第８表に示す。この表は、各化合物の表中に記載の濃度における殺虫率を示す。 (Test Example 7) Efficacy test against green peach aphid Female adult green peach aphids were released on bok choy (seventh true leaf stage) in a 3-inch pot. The next day, the female adults were removed, leaving only the first instar nymphs that had been laid.
Emulsion (I) was diluted with water to a set concentration to obtain a diluted solution (I). Emulsion (II) was diluted with water to a set concentration to obtain a diluted solution (II). The diluted solutions (I) and (II) were sprayed on the bok choy. The bok choy was then stored in a temperature-controlled room at a temperature of 25°C and a humidity of 60%.
After 6 days, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate.
The results of the test are shown in Table 8 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000069
Figure JPOXMLDOC01-appb-T000069
（試験例８）キスジノミハムシに対する効力試験
　乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。３寸鉢に植えたチンゲンサイ苗（第７本葉展開期）に希釈液(I)及び希釈液(II)を散布した。チンゲンサイ苗を風乾させ、次いでプラスチックカップに入れた。これに、キスジノミハムシ成虫１０頭を放し、温度２５℃、湿度６５％の恒温室内で保管した。
　放虫から７日間経過したときに生死判定を行い、殺虫率を算出した。試験は２反復で行った。
　試験の結果を以下の第９表に示す。この表は、各化合物の表中に記載の濃度における殺虫率を示す。 (Test Example 8) Efficacy test against Striata stripes flea beetles Emulsion (I) was diluted with water to a set concentration to obtain dilution (I). Emulsion (II) was diluted with water to a set concentration to obtain dilution (II). Dilution (I) and dilution (II) were sprayed on bok choy seedlings (at the seventh true leaf development stage) planted in 3-inch pots. The bok choy seedlings were air-dried and then placed in plastic cups. Ten adult Striata stripes flea beetles were released into the cups and stored in a thermostatic chamber at a temperature of 25°C and a humidity of 65%.
Seven days after the release of the insects, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate.
The results of the test are shown in Table 9 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000070
Figure JPOXMLDOC01-appb-T000070
Figure JPOXMLDOC01-appb-T000071
Figure JPOXMLDOC01-appb-T000071
（試験例９）ミカンキイロアザミウマ
　インゲンのリーフディスクにミカンキイロアザミウマ若虫を８頭接種した。乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。希釈液(I)及び希釈液(II)をインゲンのリーフディスクに散布し、風乾した。
　散布から７日間経過したときに生死判定を行い、殺虫率を算出した。試験は２反復で行った。
　試験の結果を以下の第１０表に示す。この表は、各化合物の表中に記載の濃度における殺虫率を示す。 (Test Example 9) Western flower thrips Eight nymphs of Western flower thrips were inoculated onto bean leaf disks. Emulsion (I) was diluted with water to a set concentration to obtain dilution (I). Emulsion (II) was diluted with water to a set concentration to obtain dilution (II). Dilution (I) and dilution (II) were sprayed onto bean leaf disks and air-dried.
Seven days after spraying, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate.
The results of the test are shown in Table 10 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000072
Figure JPOXMLDOC01-appb-T000072
（試験例１０）ネギアザミウマに対する効力試験
　インゲンのリーフディスクにネギアザミウマ若虫を８頭接種した。乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。希釈液(I)及び希釈液(II)をインゲンのリーフディスクに散布し、風乾した。
　散布から７日間経過したときに生死判定を行い、殺虫率を算出した。試験は２反復で行った。
　試験の結果を以下の第１１表に示す。この表は、各化合物の表中に記載の濃度における殺虫率を示す。 (Test Example 10) Efficacy Test Against Onion Thrips Eight onion thrips nymphs were inoculated onto green bean leaf disks. Emulsion (I) was diluted with water to a set concentration to obtain dilution (I). Emulsion (II) was diluted with water to a set concentration to obtain dilution (II). Dilution (I) and dilution (II) were sprayed onto green bean leaf disks and air-dried.
Seven days after spraying, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate.
The results of the test are shown in Table 11 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000073
Figure JPOXMLDOC01-appb-T000073
（試験例１１）チャノキイロアザミウマに対する効力試験
　ナツミカンのリーフディスクにチャノキイロアザミウマ幼虫を８頭接種した。乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。希釈液(I)及び希釈液(II)をナツミカンのリーフディスクに散布し、風乾した。
　散布から７日間経過したときに生死判定を行い、殺虫率を算出した。試験は２反復で行った。
　試験の結果を以下の第１２表に示す。この表は、各化合物の表中に記載の濃度における殺虫率を示す。 (Test Example 11) Efficacy test against tea tree thrips Eight tea tree thrips larvae were inoculated onto a Natsumikan leaf disk. Emulsion (I) was diluted with water to a set concentration to obtain a dilution (I). Emulsion (II) was diluted with water to a set concentration to obtain a dilution (II). Dilution (I) and dilution (II) were sprayed onto Natsumikan leaf disks and air-dried.
Seven days after spraying, the survival rate was determined and the mortality rate was calculated. The test was carried out in duplicate.
The results of the test are shown in Table 12 below, which shows the insecticidal rate of each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000074
Figure JPOXMLDOC01-appb-T000074
（試験例１２）ミナミキイロアザミウマに対する効力試験
　３寸鉢に植えたキュウリ苗にミナミキイロアザミウマ成虫１０頭を放した。乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。希釈液(I)及び希釈液(II)をキュウリ苗に散布し、風乾した。散布から２日間経過したときに成虫を除去した。キュウリ苗に卵が産み付けられていた。
　散布から７日間経過したときに卵から孵化した寄生幼虫を計数し、以下の式を用いて防除率を算出した。試験は２反復で行った。
　防除率（％）＝{１－（化合物処理区幼虫数／対照区幼虫数）}×１００
　試験の結果を以下の第１３表に示す。この表は、各化合物の表中に記載の濃度における防除率を示す。 (Test Example 12) Efficacy test against Thrips palmi Ten adult Thrips palmi were released on cucumber seedlings planted in 3-inch pots. Emulsion (I) was diluted with water to a set concentration to obtain diluted solution (I). Emulsion (II) was diluted with water to a set concentration to obtain diluted solution (II). Diluted solutions (I) and (II) were sprayed on cucumber seedlings and air-dried. Two days after spraying, the adult insects were removed. Eggs were laid on the cucumber seedlings.
The number of parasitic larvae that hatched from the eggs 7 days after spraying was counted, and the control rate was calculated using the following formula: The test was carried out in duplicate.
Control rate (%) = {1 - (number of larvae in compound-treated area/number of larvae in control area)} x 100
The results of the test are shown in Table 13 below, which shows the percent control for each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000075
Figure JPOXMLDOC01-appb-T000075
（試験例１３）トマトハモグリバエに対する効力試験
　３寸鉢に植えたキュウリ苗にトマトハモグリバエ成虫を接種し１日間産卵させた。乳剤(I)を設定濃度になるように水で希釈し、希釈液(I)を得た。乳剤(II)を設定濃度になるように水で希釈し、希釈液(II)を得た。希釈液(I)及び希釈液(II)を前記のキュウリに散布した。その後、キュウリを、温度２５℃、湿度６０％の恒温室内で保管した。
　６日間経過したときにマイン数（幼虫がキュウリの葉に残す食痕、あるいは潜孔の数）を計測し、以下の式を用いて防除率を算出した。試験は２反復で行った。
　防除率（％）＝{(Mc)-(Mt)/(Mc)}×１００
　Mｃ：無処理区の全長１cm以上のマイン数
　Mｔ：散布処理区の全長１cm以上のマイン数
　試験の結果を以下の第１４表に示す。この表は、各化合物の表中に記載の濃度における防除率を示す。 (Test Example 13) Efficacy test against tomato leafminers Tomato leafminers were inoculated onto cucumber seedlings planted in 3-inch pots and allowed to lay eggs for one day. Emulsion (I) was diluted with water to a set concentration to obtain dilution (I). Emulsion (II) was diluted with water to a set concentration to obtain dilution (II). Dilution (I) and dilution (II) were sprayed on the cucumbers. The cucumbers were then stored in a constant temperature room at a temperature of 25°C and a humidity of 60%.
After 6 days had passed, the number of mines (the number of feeding marks or burrowing holes left by the larvae on the cucumber leaves) was counted, and the control rate was calculated using the following formula. The test was performed in duplicate.
Control rate (%) = {(Mc)-(Mt)/(Mc)} x 100
Mc: Number of mines with a total length of 1 cm or more in the untreated area Mt: Number of mines with a total length of 1 cm or more in the spray-treated area The test results are shown in Table 14 below. This table shows the control rate for each compound at the concentration shown in the table.
Figure JPOXMLDOC01-appb-T000076
Figure JPOXMLDOC01-appb-T000076
　本発明の（ヘテロ）アリールウレア化合物は、殺虫活性に優れ、安全性に優れ且つ工業的に有利に合成できる。
　本発明の殺虫剤は、農業害虫を低濃度で効果的に防除することができる。 The (hetero)aryl urea compound of the present invention has excellent insecticidal activity, is safe, and can be synthesized industrially advantageously.
The insecticide of the present invention can effectively control agricultural pests at low concentrations.

Claims (2)

  1. 　式（Ｉ）で表される化合物またはその塩。
    Figure JPOXMLDOC01-appb-C000001
     （式（Ｉ）中、
    　Ａ１は、窒素原子、またはＣＨで表される基を示し、
    　Ｒ１は、Ｃ１～６ハロアルコキシ基、またはＣ１～６ハロアルキルチオ基を示し、
    　Ｒaは、水素原子、または置換若しくは無置換のＣ３～６シクロアルキル基を示し、
    　Ｂ１は、窒素原子、またはＣＨで表される基を示し、
    　Ｂ２は、窒素原子、またはＣＸｂで表される基を示し、
    　ＸａおよびＸｂは、それぞれ独立に、水素原子、Ｃ１～６ハロアルコキシ基、ハロゲノ基、カルバモイル基、チオカルバモイル基、またはシアノ基を示す。）     A compound represented by formula (I) or a salt thereof.
    Figure JPOXMLDOC01-appb-C000001
     (In formula (I),
    A 1 represents a nitrogen atom or a group represented by CH;
    R 1 represents a C1-6 haloalkoxy group or a C1-6 haloalkylthio group;
    R a represents a hydrogen atom or a substituted or unsubstituted C3-6 cycloalkyl group;
    B1 represents a nitrogen atom or a group represented by CH;
    B2 represents a nitrogen atom or a group represented by CXb ;
    Xa and Xb each independently represent a hydrogen atom, a C1-6 haloalkoxy group, a halogeno group, a carbamoyl group, a thiocarbamoyl group, or a cyano group.
  2. 　請求項１に記載の化合物またはその塩からなる群から選ばれる少なくとも１つを有効成分として含有する殺虫剤。 An insecticide containing at least one selected from the group consisting of the compound or salt thereof according to claim 1 as an active ingredient.
PCT/JP2023/038749 2022-11-10 2023-10-26 (hetero)aryl urea compound and insecticide WO2024101172A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2022-180255 2022-11-10
JP2022180255 2022-11-10

Publications (1)

Publication Number Publication Date
WO2024101172A1 true WO2024101172A1 (en) 2024-05-16

Family

ID=91032723

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2023/038749 WO2024101172A1 (en) 2022-11-10 2023-10-26 (hetero)aryl urea compound and insecticide

Country Status (1)

Country Link
WO (1) WO2024101172A1 (en)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62185065A (en) * 1986-01-30 1987-08-13 チバ−ガイギ−　アクチエンゲゼルシヤフト N-(4-(haloalkoxy)trifluoromethylphenyl)-n'-benzoylurea, manufacture and vermicidal use
JP2017523162A (en) * 2014-07-23 2017-08-17 ダウ アグロサイエンシィズ エルエルシー Molecules with certain agrochemical applications, intermediates, compositions and methods relating thereto
WO2020229398A1 (en) * 2019-05-14 2020-11-19 Bayer Aktiengesellschaft (1-alkenyl)-substituted pyrazoles and triazoles as pest control agents
WO2022157188A2 (en) * 2021-01-23 2022-07-28 Syngenta Crop Protection Ag Pesticidally active heteroaromatic compounds
WO2022244795A1 (en) * 2021-05-21 2022-11-24 日本曹達株式会社 Heteroaryl compound and pest control agent

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62185065A (en) * 1986-01-30 1987-08-13 チバ−ガイギ−　アクチエンゲゼルシヤフト N-(4-(haloalkoxy)trifluoromethylphenyl)-n'-benzoylurea, manufacture and vermicidal use
JP2017523162A (en) * 2014-07-23 2017-08-17 ダウ アグロサイエンシィズ エルエルシー Molecules with certain agrochemical applications, intermediates, compositions and methods relating thereto
WO2020229398A1 (en) * 2019-05-14 2020-11-19 Bayer Aktiengesellschaft (1-alkenyl)-substituted pyrazoles and triazoles as pest control agents
WO2022157188A2 (en) * 2021-01-23 2022-07-28 Syngenta Crop Protection Ag Pesticidally active heteroaromatic compounds
WO2022244795A1 (en) * 2021-05-21 2022-11-24 日本曹達株式会社 Heteroaryl compound and pest control agent

Similar Documents

Publication Publication Date Title
US11884633B2 (en) Arylazole compound and pest control agent
IL282553B2 (en) (hetero)arylimidazole compound and harmful organism control agent
JP7551632B2 (en) Pest control method, pest control composition, and pest control set
WO2020050212A1 (en) Heteroaryl azole compound and pest control agent
US11078181B2 (en) Diaryl pyrazole compound and formulation for controlling harmful organisms
JP7532355B2 (en) Pyridinium salts and pest control agents
US20220267272A1 (en) Pyridinium salt and pest control agent
JP7510425B2 (en) Onium salts of nitrogen-containing heteroaryl compounds and pest control agents
US20230357232A1 (en) Imidazo[1,2-a]pyridine compound and pest control agent
US11427564B2 (en) Heteroaryl pyrimidine compound and pest control agent
JP2024096532A (en) Methinyl urea compound and pest control agent
JP2023077429A (en) Benzamide compounds and pest control agent
WO2024101172A1 (en) (hetero)aryl urea compound and insecticide
TWI677493B (en) Oxadiazoline compound and harmful organism control agent
TW202110804A (en) Pyridinium salt and pest control agent
JP2024084158A (en) Benzimidazole compound and harmful organism controlling agent
KR20240008308A (en) (Hetero)arylamide compounds and harmful organism control agents

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23888520

Country of ref document: EP

Kind code of ref document: A1