KR100804452B1 - Cyclic amine compound and pest control agent - Google Patents

Abstract

The compound represented by general formula (I) is disclosed. Salt and N-oxides of the compounds represented by the formula (I), and pest control agents comprising the compound of the formula (I) as an active ingredient are also disclosed.

[Formula I]

[Wherein, R ¹ represents a hydroxyl group or the like;

m represents 0 or an integer from 1 to 5;

R ² represents a halogen atom or the like;

k represents 0 or an integer from 1 to 4;

R ³ , R ³¹ , R ⁴ , R ⁴¹ , R ⁵ , R ⁵¹ , R ⁶ , R ⁶¹ and R ⁷ independently represent a hydrogen atom or the like;

X represents an oxygen atom or the like;

n represents 0 or 1].

Description

Cyclic amine compound and harmful biological control agent {CYCLIC AMINE COMPOUND AND PEST CONTROL AGENT}

The present invention relates to novel cyclic amine compounds and harmful biological control agents containing such compounds as active agents.

The present invention relates to Japanese Patent Application No. 2004-106668 filed on March 31, 2004, and Japanese Patent Application No. 2004-374007 filed on December 24, 2004, the contents of which are incorporated herein by reference. Claim with priority.

Although many pesticides and acaricides are commonly used, they are satisfactory because of their inadequate effects, resistance problems that limit their use, potential for chemical damage or contamination to plants, or because of their great toxicity to humans, emery, fish, etc. It is too difficult to be regarded as. Therefore, there is a need to develop an agent which can be used safely with little of the above problems.

Although compounds having a skeleton similar to those of the compounds of the invention have been described as antiviral agents in European Patent Application No. 0 605 031, their pesticidal and acaricide activity has not been described and the synthesis and biological activity of the compounds of the invention have not yet been reported. none.

It is an object of the present invention to provide novel compounds which can be provided as pest control agents which can be synthesized to be commercially profitable and can be used safely with certain effects.

That is, the present invention is a compound represented by Formula I:

[Wherein, R ¹ is a hydroxyl group, a halogen atom, a cyano group, a nitro group, a formyl group, which may be substituted with G _¹ C ¹ _-6 alkyl, C _{2 -6} alkenyl group, C _{2 -6} alkynyl group, C _{1 -6} haloalkyl, C _{1 -6} haloalkenyl group, C _{1 -6} alkyl group, a C _{1 -6} alkoxy group which may be substituted with G ^2, C _1-6 haloalkoxy group, C _{2 -6} alkenyloxy group group, a halo-C _{2 -6} alkenyl group, a C _{2 -6} alkynyl group, a C _{1 -6} alkylcarbonyloxy group, C _{1 -6} alkoxy carbonyloxy group, C _{1 -6} alkylthio carbonyloxy group, G ³ import amino, C _{1 -6} alkyl group which may be substituted by, C _1-6 haloalkylthio, C _{1 -6} alkoxy group, C _{1 -6} haloalkylsulfinyl group, C _{1 -6} alkyl sulfonyl group , C _{1 -6} haloalkylsulfonyl group, C _{1 -6} alkylsulfonyl group, a C _{1 -6} haloalkylsulfonyl group, a heterocyclic group which may be substituted with G ⁴ (an oxygen atom, selected from nitrogen atom and sulfur atom, 5 or 6 members with one or more heteroatoms Heterocyclic group), or any one substituent represented by the following formula:

(Wherein R ⁸ and R ⁹ each independently represent a C _1-6 alkyl group, Y ¹ , Y ² and Y ³ each independently represent an oxygen atom or a sulfur atom, and A may be substituted with G ⁴ ) Heterocyclic group (a 5 or 6 membered heterocyclic group having one or more heteroatoms selected from an oxygen atom and a nitrogen atom), R ¹⁰ represents a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, C _1-6 alkyl C _1-6 alkoxy group, C _1-6 haloalkyl group, or a heterocyclic group which may be substituted with G ⁴ (5 or 6 having one or more heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom) Ring heterocyclic group), R ¹¹ and R ¹² each independently represent a hydrogen atom, a C _1-6 alkyl group, a C _2-6 alkenyl group or a C _2-6 alkynyl group, and R ¹³ and R ¹⁴ each independently A C _1-6 alkyl group, R ¹³ and R ¹⁴ may be bonded together to form a ring}; m represents 0 or an integer from 1 to 5,

R ² is a halogen atom, a nitro group, C _{1 -6} alkyl, C _{1 -6} alkoxy, C _{1 -6} haloalkyl group, a heterocyclic group (an oxygen atom which may be substituted with G ^4, which is selected from nitrogen and sulfur atoms 5 or 6 membered heterocyclic group having one or more heteroatoms), or a C _{1 -6} represents a haloalkoxy group, k is 0 or an integer of 1 to 4;

^{R 3, R 31, R 4} , R 41, R 5, R 51, R 6, R 61 and R ⁷ are each independently hydrogen atoms, C _{1 -6} alkyl, C _{1 -6} alkoxycarbonyl group or a C _{1 -6} An alkoxy group, R ³ and R ⁴ may be taken together or R ⁵ and R ⁶ may be bonded together to form a saturated ring,

X represents an oxygen atom, a sulfur atom, a sulfinyl group or a sulfonyl group,

G ¹ is hydroxyl group, C _{1 -6} alkoxycarbonyl, C _{1 -6} alkoxy, C _{1 -6} alkoxy C _1-6 alkoxy group, a heterocyclic group which may be substituted with G ⁴ (oxygen atom, nitrogen atom and sulfur 5 or 6 membered heterocyclic group having one or more heteroatoms selected from atoms), or a C _3-6 cycloalkyl group,

G ² is hydroxyl group, a cyano group, G ^4, which may be substituted by amino, C _{1 -6} alkoxycarbonyl, C _{1 -6} alkylthio groups, C _{1 -6} alkylsulfonyl, C _{1 -6} alkoxy, C _1-6 alkoxycarbonyl C _1-6 alkoxy group, C _{3 -6} cycloalkyl group, or a halogen atom or a C ₁ represents a C _{6 -10} aryl group which may be substituted with _-6 alkyl group,

G ³ is a C _{1 -6} alkyl, C _{1 -6} alkyl group or a C _{1 -6} represents an alkylsulfonyl,

G ⁴ is a C _{1 -6} alkyl group, or represent a C _{1 -6} alkoxy group,

n represents 0 or 1]

A salt or N-oxide of a compound represented by the formula (1) and a pest control agent comprising the same as an active ingredient are provided.

Best Mode for Carrying Out the Invention

In the present invention, examples of the halogen atom in the formula (I) may include fluorine, chlorine, bromine, iodine and the like.

Examples of C _{1 -6} alkyl group may include methyl, ethyl, propyl, isopropyl, cyclopropyl, n- butyl, sec- butyl, isobutyl, t- butyl, pentyl and its isomers, hexyl and its isomers.

Examples of C _2-6 alkenyl include ethenyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-methyl- 2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-butenyl, 1-hexenyl, 2- Hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl and the like.

Examples of C _2-6 alkynyl ethynyl group, the 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 2-methyl- 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl2-butynyl, 2-methyl-3-pentynyl, 1-hexynyl, 1,1 -Dimethyl-2-butynyl and the like.

Examples of C _{1 -6} haloalkyl groups include chloromethyl, fluoromethyl, bromomethyl, dichloro-methyl, difluoro-methyl, di-bromo-methyl, methyl, trifluoromethyl, methyl trichlorosilane, mono-bromo-difluoro-methyl-Mo, Trifluoroethyl, 1-chloroethyl, 2-chloroethyl, 1-bromoethyl, 2-bromoethyl pentafluoroethyl, 1-fluoropropyl, 2-fluoropropyl, and the like.

C _{1 -6} illustrate a haloalkenyl group is 3-chloro-2-propenyl, 3,3-dichloro-2-propenyl, 4-chloro-2-butenyl, 4,4-dichloro-3-butenyl oxy , 4,4-difluoro-3-butenyloxy and the like.

Examples of C _1-6 alkylcarbonyl group may include methyl-carbonyl, ethyl-carbonyl, propyl-carbonyl, butyl carbonyl.

Examples of C _1-6 alkoxy group may include such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec- butoxy, isobutoxy, t- butoxy and the like.

C _{1 -6} Examples of haloalkoxy groups include chloromethoxy, dichloro methoxy, Romero trichloro ethoxy, trifluoromethoxy, difluoromethoxy-bromo-modify, in a 1-fluoro-ethoxy, 2-trifluoroethoxy, 2-chloro Ethoxy, 2-bromoethoxy, 1,1-difluoroethoxy, fluoroethoxy, 1,1-difluoroethoxy, 3-chloropropoxy and the like.

Examples of the C _2-6 alkenyloxy group may include vinyloxy, allyloxy, allenyloxy, butenyloxy, 3-methyl-2-butyleneoxy, and the like.

Examples of C _{2 -6} haloalkyl alkenyloxy group include 3-chloro-2-propenyloxy, 3,3-dichloro-2-propenyloxy, 4-chloro-2-butenyl-oxy, 4,4-dichloro-2 -Butenyloxy, 4,4-difluoro-3-butenyloxy, and the like.

C _{2 -6} alkynyl ethynyl example of aryloxy group optionally has, propargyl may be included, such as oxy, 2-propynyl-oxy, 2-butynyl-oxy, 1-methyl-2-propynyl oxy.

Examples of C _{1 -6} alkylcarbonyloxy group may include such as acetyloxy, propionyloxy, butyryl oxy.

Examples of C _{1 -6} alkoxy carbonyloxy group may include such as methoxy carbonyloxy, ethoxycarbonyloxy.

Examples of C _{1 -6} alkylthio carbonyloxy group may include a methyl thio carbonyl-oxy, ethylthio carbonyloxy.

Examples of C _{1 -6} alkylthio group may include methyl thio, ethyl thio, propyl thio.

Examples of C _{1 -6} haloalkylthio has monofluorophosphate as methylthio, difluoromethyl methylthio, trifluoromethyl be included, such as methylthio.

C _{1 -6} illustrate the alkylsulfinyl group may include a methyl sulfinyl, ethyl sulfinyl, propyl sulfinyl.

Examples of C _{1 -6} haloalkylsulfinyl group may include ethyl sulfinyl methyl, methylsulfinyl, pentafluoroethyl trifluoromethyl.

C _{1 -6} illustrate the alkylsulfonyl group may include such as methylsulfonyl, ethanesulfonyl.

C _{1 -6} haloalkyl Examples of alkylsulfonyl group may include such as trifluoromethyl sulfonyl, pentafluoroethyl sulfonyl.

C _{1 -6} illustrate the alkylsulfonyloxy group may include such as methyl sulfonyloxy, ethane sulfonyloxy.

Examples of C _{1 -6} haloalkyl sulfonyloxy group may include such as trifluoromethyl sulfonyloxy, pentafluoro-butyl Ro sulfonyloxy.

Examples of C _{1 -6} alkoxy-alkoxy group might include the methoxymethoxy, methoxyethoxy, ethoxy-methoxy.

Examples of C _{3 -6} cycloalkyl group include cyclopropyl, 1-methylcyclopropyl, 2,2,3,3-tetramethyl-cyclopropyl, cyclobutyl, cyclopentyl, 1-methylcyclopentyl, cyclohexyl, 1-methylcyclohexyl Hexyl, 4-methylcyclohexyl, and the like.

Examples of C _6-10 aryl group may include phenyl, naphthyl and the like.

Examples of 5 or 6 membered heterocyclic groups having at least one heteroatom selected from oxygen, nitrogen and sulfur atoms include tetrahydrofuryl, dioxolanyl, 1,2,3-oxadiazolyl, oxazolyl, 1,3 Dioxolanyl, thienyl, pyridyl, 4,5-dihydrofuryl, furyl and the like.

m represents 0 or the integer of 1-5. When there are several R ¹ , each of them may be the same or different.

In formula (I), R ³ and R ⁴ may be together or R ⁵ and R ⁶ together may form a saturated ring. R ³ and R ⁴ together or R ⁵ and R ⁶ together can form a saturated ring to form a crosslinked ring as a whole, for example:

8-azabicyclo [3.2.1] octane ring (hereinafter referred to as tropan ring),

3-azabicyclo [3.2.1] octane ring (hereinafter referred to as isotropane ring),

3-azabicyclo [3.3.1] nonane and the like.

Furthermore, there are also compounds prepared by the oxidation of the nitrogen atom of the nitrogen atom of the pyridine ring of the general formula (I) of the present invention or of a cyclic amine moiety such as a piperidine ring, a tropane ring, and all of these N-oxides. Included in

When R ³ and R ⁴ together or R ⁵ and R ⁶ together form a saturated ring in the compound of the formula (I) of the present invention, there are two kinds of isomers respectively shown in the following examples. These isomers are not intended to fall within the scope of the present invention and are intended to belong without exception.

Next, the manufacturing method of the compound of this invention is demonstrated. First, the manufacturing method of the intermediate body 3 is demonstrated.

(Wherein R ¹ to R ⁷ , R ³¹ , R ⁴¹ , R ⁵¹ , R ⁶¹ , m and n have the same meanings as in formula (I), and X ¹ and X ² are each independently a hydroxyl group or a thiol) X ³ represents a leaving group such as a halogen atom, X ⁴ represents an oxygen atom or a sulfur atom, and R represents any of a 2-pyridyl group, a methyl group and a benzoyl group substituted with R ² _k ).

As shown in Scheme III, Intermediate 3 is a Mitsunobu reaction between, for example, a compound of Formula (1) and a compound of Formula (2) (eg, Tetrahedron Lett., 1978, 2243, J. Org. Chem., 50, 3095, 1985, etc.). Compounds of formula (1) can be prepared by known methods (eg, those described in "The Chemistry of Phenols", Eds. Z. Rappoport, J. wiley (2003), Part 1, pp 395, and the like).

Alternatively, intermediate (3) can also be prepared by coupling an aryl halide (4) with a compound of formula (2) as shown in Scheme IV. Specifically, known methods (eg, Synth. Commun., 1984, 14, 621; J. Org. Chem., 48, 3771 (1983); J. Med. Chem., 17, 1000 (1974), etc. ) Can be prepared.

Examples of bases that can be used in this case include alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and the like, carbonates such as sodium carbonate, potassium carbonate and the like, metal alkoxides such as sodium methoxide, potassium t-butoxide, magnesium ethoxy Seeds and the like, organic metals such as n-butyllithium, LDA and the like, metal hydrides such as sodium hydride, potassium hydride and the like, organic bases such as triethylamine, diisopropylamine, pyridine and the like. The reaction can be carried out in the presence of a solvent or in the absence of a solvent. The solvents that can be used are not particularly limited, provided that they are chemically stable solvents, and examples thereof include hydrocarbon base solvents such as pentane, hexane, heptane, benzene, toluene, xylene and the like, halogen base solvents such as dichloromethane, 1 Nitrile base solvents such as, 2-dichloroethane, chloroform, carbon tetrachloride, such as acetonitrile, propionitrile and the like, ether base solvents such as diethyl ether, dioxane, tetrahydrofuran and the like, aprotic polar solvents such as N, N Dimethylformamide (DMF), dimethylsulfoxide (DMSO), and the like, and mixed solvents comprising two or more of the above solvents may be included. The reaction can be carried out at any temperature in the range of −78 ° C. to the melting point of the solvent used.

When R in formula (2) is a 2-pyridyl group substituted with R ² (compound (7)), the compound of formula (I) can be prepared directly according to scheme III or scheme IV.

As shown in Scheme V, the compound of compound (7) can be synthesized by coupling between amine (5) and 2-halopyridine (6). Specifically, it can be prepared by known methods (eg, those described in Synthesis, 1981, 616; J. Chem. Soc., C, 3693 (1971), etc.).

Wherein R ² to R ⁷ , R ³¹ , R ⁴¹ , R ⁵¹ , R ⁶¹ , n, X ² and X ³ represent the same meanings as described above.

In contrast, when R in compound (2) is a methyl group or benzyl group, intermediate (3) prepared by Scheme III or Scheme IV must be demethylated or debenzylated. Demethylation can be performed by known methods (eg, Tetrahedron Lett., 1974, 1325; document 1977, 1565; document 1995, 8867 and the like). Furthermore, debenzylation can be carried out using known dehydrogenation. As shown in Scheme VI, the compounds of formula (I ′) of the present invention can be prepared by the preparation of intermediate (8) from intermediate (3) followed by coupling with 2-halopyridine (6). The specific method of the coupling is the same as in Scheme V.

As with the compound of compound 2, wherein R is a methyl group or benzyl group, a commercial product can be used directly. Intermediate (8) may be present alone as an amine or may form a salt with hydrochloric acid, acetic acid and the like.

After completion of the above-mentioned condensation reaction, if necessary, purification of the obtained product can be carried out according to known conventional methods such as distillation, recrystallization, column chromatography and the like.

Compounds of the present invention (compounds represented by Formula I, salts thereof or N-oxides) include harmful organisms in agriculture, hygienic harmful insects, harmful insects in grain storage, harmful insects in textile storage, harmful pests at home, and the like. It can be used for control and has killing activity against adult, pupa, larva and eggs. Examples of each of these are shown below.

Examples of insect pests include tobacco castor moth larvae, thief moths, arrested moths, Chinese cabbage butterfly, worms, Chinese cabbage moth, apple chick pattern moth, tea leaf roller, peach hearted moth, and peach shoot Moth, orange moth, tea leaf roller, apple moth, cicada moth, poison moth, rice stem border, wild moth, european corn border, white light moth Moths, Heliothis sp., Heliciverpa sp., Agrotis sp., Casemaking clothes moth, apple moths and cottonseed worms.

Examples of fern pests include peach hump aphids, cotton aphids, tulip aphids, grain aphids, sawtooth ant bugs, grass-colored bugs, arrowworms, mulberry mealy scale, greenhouse powder, tobacco powder, Silver leaf flour, Pear tree, Pear shield beetle, Pleurotus larvae, larvae, white locusts and cicada larva

Examples of crustacean pests include flea leaf beetles, sesame leaf beetle, colorado potato beetle, rice weevil, red bean weevil, beetle, beetle, diabrotica spp., Diabrotica sp. White-spotted longicom beetle, Agriotis sp., 28 spotted ladybug, false rice thief, and cotton weevil.

Examples of bicot pests include housefly, black fly, drifting fly, green fruit fly, citrus fruit fly, seed maggot, rice leaf waterfly, yellow fruit fly, chimpanzee, and culex tritaeniarhynchus. ), Egyptian forest mosquito (Aedes aegypti) and Chinese spotted mosquito (Anopheles sinensis).

Examples of Thysanopterous pests include cucumber thrush and chafer worms.

Examples of logging pests include Monomorium pharaonis, yellow hamet, and leafless bees.

Examples of direct-infested pests include Bellows, German wheels, American wheels, and Japanese wheels.

Examples of termite pests include Formosan subterranean termite and Reticulitermes speratus Kolbe.

Examples of Aphanipterous pests include human fleas.

Examples of Anoplurous pests include humans.

Examples of mites include spotted mite, spotted mite, tea mite, tangerine mite, apple mite, tangerine mite, apple rust mite, Tarsonemus sp., Brevipalpus sp., Root mite, Common grain mite, house dust mite (Dermatophagoides farinae), tailed mite (Boophilus microplus) and Haemaphysallis bispinosa.

Examples of plant-parasitic nematodes include sweet potato root nematodes, root rot nematodes, soybean crust nematodes, rice ear nematodes and pine nematodes.

Among the pests mentioned above, Pseudomonas pests, Pseudomonas pests, mites, Tisanophtherus pests and Carpacetic pests are preferred targets of the compounds of the invention, in particular mites are the most preferred targets.

In recent years, various pests such as Chinese cabbage moth, planthopper, planthopper, aphid and the like have developed resistance to organophosphorus insecticide, carbamate insecticide, acaricide and the like. Thus, the pesticides and acaricides mentioned above lost their influence on the pests and mites that developed resistance to them. Thus, there is a need for the development of compounds that are effective against resistant strains and mites. The compounds of the present invention are compounds having excellent insecticidal and acaricide effects against sensitive species as well as mites resistant to organic phosphorus insecticides, carbamate insecticides or pyrethroid insecticides.

The compounds of the present invention induce very weak phytotoxicity for plants, low toxicity for fish and warm blooded animals, and are very safe.

Moreover, the compounds of the present invention can also be used as antifouling agents that prevent the attachment of underwater attachment organisms to underwater structures such as hull bottom surfaces and fishing nets.

The compounds of the present invention may exhibit bactericidal activity, herbicidal activity, plant control activity. Moreover, intermediate compounds of the compounds of the present invention may have pest and tick killing activity.

Insecticides and acaricides of the present invention may include one or more compounds of the present invention as their active ingredients. Although the compounds of the present invention may be used directly without other additives, they are generally mixed with solid carriers, liquid carriers or gas carriers or impregnated with a base such as porous ceramic plates, nonwoven fabrics, etc., and then, if necessary, surfactants or other Auxiliaries can be added to them in the form of conventional pesticides, namely water dispersible powders, granules, dusting powders, emulsions, water soluble powders, suspensions, granular water dispersible powders, floatable, aerosols, misting agents, heat computing agents, smoke agents , Poison, microcapsules and the like.

When the compound is used as a solid agent, vegetable powders such as soybean grains, wheat flour, mineral powders such as diatomaceous earth, apatite, gypsum, talc, bentonite, kaolin, clay and the like, organic or inorganic compounds such as soda urea, urea, yellowish yellow And the like can be used as an additive or a carrier. When the compound is used as a liquid, petroleum fractions such as kerosene, xylene and solvent naphtha, such as cyclohexane, cyclohexanone, dimethylformamide, dimethyl sulfoxide, alcohols, acetone, methyl isobutyl ketone, mineral oil, vegetable Oils, water and the like can be used as the solvent. As the gas carrier for the propellant, butane gas, LPG, dimethyl ether or carbonic acid gas may be used.

Examples of the poison substrate include grain powder, vegetable oil, sugar, crystalline cellulose and the like, antioxidants such as dibutylhydroxytoluene, nordihydroguairetic acid, preservatives such as dihydroacetic acid, and the like for children or pets. Ingestion inhibitors such as powdered capsicum and the like or pest attractant flavors such as cheese and onion flavor can be used.

If desired, surfactants may be added to the formulation to form stable forms. There is no limitation on the surfactant, but examples thereof include nonionic surfactants such as alkyl ethers with polyoxyethylene, higher fatty acid esters with polyoxyethylene, sorbitan higher fatty acid esters with polyoxyethylene, poly Sulfuric acid ether salts of alkylphenyl ethers added with polyoxyethylene, alkylnaphthalene sulfonates, polycarboxylates, formaldehyde condensates of alkylnaphthalene sulfonates, such as tristyrylphenyl ether added with oxyethylene, Copolymers of isobutylene-maleic anhydride and the like.

When the compounds of the present invention are used in pest control on farms, the amount of active ingredient is from 0.01 to 90% by weight, preferably from 0.05 to 85% by weight, which can be used as a solution, suspension or emulsion, where its moisture Acidic powders, emulsions, suspensions, floorables, water-soluble powders or granular water-soluble powders can be diluted in water to their prescribed concentrations and, if they are dusting powders or granules, they can be used by spraying them on plants or soil.

In the case of using the compound of the present invention for prevention, if they are an emulsion, a water dispersible powder, and a flooring agent, they can be used by diluting them with water up to a predetermined concentration thereof, or they are oil solutions, aerosols, aerosols, poisons, mites prevention sheets. Etc., these can be used directly.

When the compound of the present invention is used as a pest control agent for controlling external parasites of cattle such as cattle, pigs, or pets such as dogs and cats, the formulation of the compound of the present invention is generally used as a veterinary known method. use. The method may, for example, consider a method of administration such as tablets, capsules, penetrants, feed admixtures, suppositories, injections (intramuscular, subcutaneous, intravenous, intraperitoneal, etc.), for the purpose of systemic inhibition, vision For the purpose of novel application, methods of administering oily or aqueous liquids, such as spraying, injecting, dropping, and the like, and methods of wearing materials prepared by molding the resin formulation into suitable forms, such as collars, ear tags, and the like. This includes. In this case, the compounds of the present invention are used at a ratio of 0.01 to 1000 mg per kg of the subject animal.

It is natural that the compounds of the present invention can be used alone to exert their full effect, and they are also used in other pest control agents, fungicides, insecticides, acaricides, herbicides, plant growth regulators, fertilizers, soil improvers, animal feeds and the like. May be mixed or used together.

Typical examples of active ingredients such as fungicides, insecticides, acaricides, plant growth regulators, and the like, which may be mixed with or used with the compounds of the present invention are presented below.

Fungicides:

Kamtan, Polpet, Thiuram, Jiram, Zineb, Manev, Mancozeb, Propineb, Polycarbamate, Chlorotalonyl, Quindozen, Captapol, Iprodione, Prosmidone, Vinclozoline, Fluorine Leumid, cymoxanyl, mepronyl, flutolanil, pencicuron, oxycarboxine, pocetyl-aluminum, propamocarb, triadimefon, triadimenol, propiconazole, diclobutorazole, b Tertanol, hexaconazole, microbutanyl, flusilazole, etaconazole, fluorotrimazole, flutrifen, fenconazole, diconazole, ciproconazole, phenarimol, tripleluminazole, prochloraz , Imizalil, Pepurazoate, Tridemorph, Phenpropimorph, Triporin, Butiobate, Pyrfenox, Aniazine, Polyoxin, Metallaxyl, Oxadixyl, Furallaxyl, Isoprothiolane, Pro Benazol, Pyrronitrin, Blastisidin S, Kasugamycin, Validamycin, Hydrostreptomycin sulfate, benomil, carbendazim, thiophanate methyl, himexazole, basic copper chloride, basic copper sulfate, pentin acetate, triphenyltin hydroxide, dietofencarb, metasulfocarb, quinomethionate , Vinacryl, lecithin, sodium bicarbonate, dithianon, dinocarb, phenaminosulf, diclomezine, guazin, dodine, IBP, edinphenfos, mepanipyrim, perimzone, tricamide, metasulfo Carb, Fluazinam, Etoquinolak, Dimethomorph, Pycoolulone, Teclophthalam, Phthalide, Phenazine Oxide, Thiabendazole, Tricyclozole, Vinclozoline, Simoxanyl, Cyclobutanyl, Gu Azatin, propamocarb hydrochloride, oxolinic acid, and the like.

Organophosphorus and carbamate based pesticides:

Pention, Phenythrothione, Diazinon, Chlorpyriphos, ESP, Bamidothione, Pentoate, Dimethoate, Formomones, Malathion, Trichlorphone, Tiomethone, Posmet, Dichlorbos, Acetate , EPBP, methyl parathion, oxydemethone methyl, ethion, salityone, cyanophosph, isoxation, pyridapention, phosphalone, methidionone, sulfprop, chlorfenbinfos, tetrachlorobinfoss, Dimethylbinfos, propaphos, isofenfoss, ethyl thiomethone, propenophos, pyraclophos, monocrotophos, azinfos methyl, aldicarb, metomil, thiodicarb, carbofuran, carbosulfan , Benfuracarb, furathiocarb, propoxur, BPMC, MTMC, MIPC, carbaryl, pyrimiccarb, thiophencarb, phenoxycarb, cartope, thiocyclam, bensultope and the like.

Pyrethroid Based Pesticides:

Fermethyrin, Cypermethyrin, Deltamethyrin, Fenvaleric, Penpropatrine, Pyrethrin, Alletrin, Tetramethrin, Lecimetrin, Dimethrin, Propatrine, Phenotrin, Protrin Fluvalinate, Cyfluthrin, Cyhalothrin, Flucitrinate, Etophenoprox, Cycloprotrin, Tralomethrin, Silafluorene, Acrinatrin, and the like.

Benzoylurea bases and other pesticides:

Diflubenzuron, chlorfluazuron, hexaflumuron, triflumuron, tetrabenjuron, flufenoxuron, fluxycloxone, buprofezin, pyriproxyfen, metoprene, benzoepine, diafethiuron, Imidacloprid, acetamiprid, fipronil, nicotine sulfate, rotenone, metaldehyde, machine oil, BT and microbial pesticides such as insect pathogenic viruses and the like.

Nematicides:

Phenamifos, phostiazete and the like.

Acaricides:

Chlorobenzylate, phenisobromolate, dicopol, amitraz, BPPS, benzomate, hexathiax, fenbutatin oxide, polynactin, quinomethionate, CPCBS, tetradipon, avermectin, Milvemectin, clofentezin, hexahexatin, pyridaben, fenpyroximate, tebufenpyrad, pyrimidipene, phenothiocarb, dienochlor and the like.

Plant Growth Regulators:

Gibberellin (eg, Gibberellin A3, Gibberellin A4, Gibberellin A7) IAA, NAA

Example

In the following, the present invention will be described in more detail by examples, but the present invention is not limited to these examples.

Production Example  One

Preparation of 4- [4-nitro-3- (trifluoromethyl) phenoxy] -1- [5- (trifluoromethyl) -2-pyridyl] -piperidine (Compound 1-39)

Triethylamine (4.5 g) is added to an ethanol solution (25 ml) of 4-hydroxypiperidine (3.0 g) and 2-chloro-5-trifluoromethylpyridine (5.4 g), and the mixture is overnight Heated. Water was poured into the mixture and subjected to extraction with chloroform. Its organic layer was washed with water and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to afford compound (10) (5.98 g), which was used for subsequent reaction.

A compound of formula (10) (4.9 g), 5-hydroxy-2-nitrobenzotrifluoride (3.2) while cooling a THF (30 ml) solution of azodicarboxylic acid diisopropyl ester (4.3 g) with ice g) and triphenylphosphine (5.6 g) were added dropwise to a solution in THF (30 ml). The mixture was warmed to room temperature, then stirred for 3 hours and concentrated under reduced pressure. The residue was purified by column chromatography to give the above-mentioned title compound (5.98 g).

Viscous oil

Preparation Example 2

Preparation of 4- [4-amino-3- (trifluoromethyl) phenoxy] -1- [5- (trifluoromethyl) -2-pyridyl] -piperidine (Compound 1-168)

Zinc powder (18.8 g) and potassium chloride dihydrate (1.9 g) were added to an ethanol (300 ml) solution of piperidine (Compounds 1-39, 5.7 g) prepared in Preparation Example 1, and the mixture was heated to reflux overnight. did. After the mixture was cooled to room temperature, it was filtered through a pad of CELITE and the filtrate was concentrated under reduced pressure. The residue was diluted with chloroform, washed and dried over anhydrous magnesium sulfate. Its solvent was evaporated under reduced pressure to give the title compound (5.4 g).

Preparation Example 3

Preparation of 4- [4-chloro-3- (trifluoromethyl) phenoxy-1- [5- (trifluoromethyl) -2-pyridyl] -piperidine (Compound 1-15)

t-butyl nitride (0.13 g) was added dropwise to the acetonitrile suspension (5 ml) of copper (II) chloride (0.14 g) while cooling with ice. After the mixture was stirred for 10 minutes, an acetonitrile (3 ml) solution of piperidine (Compound 1-168) prepared in Preparation Example 2 was added while cooling with ice. The mixture was warmed to room temperature and stirred for further 1 hour. Pour ice water into the mixture and apply to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (0.2 g).

Preparation Example 4

4- [4-Bromo-3- (trifluoromethyl) phenoxy] -1- [5- (trifluoromethyl) -2-pyridyl] -piperidyl] -piperidine (Compound 1 -23)

t-butyl nitrite (0.12 g) was added dropwise to the acetonitrile (5 ml) suspension of copper (II) bromide (0.22 g) while cooling with ice. After the mixture was stirred for 10 minutes, a solution of acetonitrile (2 ml) of piperidine (Compound 1-168, 0.32 g) prepared in Preparation Example 2 was added while cooling with ice. After the mixture was raised to room temperature, the mixture was further stirred for 2.5 hours. Pour ice water into the mixture and apply to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. Its residue was purified by column chromatography to give the title compound (0.21 g) mentioned above.

Preparation Example 5

4- [4-bis (methylsulfonyl) amino-3- (trifluoromethyl) phenoxy] -1- [5-trifluoromethyl-2-pyridyl] piperidine (Compound 1-178) Produce

Methane sulfonyl chloride (0.09 g) and triethylamine (0.08 g) were added to a THF (5 ml) solution of piperidine (Compound 1-168, 0.32 g) prepared in Example 2, cooling with ice. The mixture was warmed to room temperature, then stirred for 4 hours, heated at reflux for 3.5 hours and further refluxed. After the mixture was cooled to room temperature, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (0.20 g).

Amorphous

Preparation Example 6

4- [2-methoxymethoxy-4- (trifluoromethyl) -phenoxy] -1- [5- (trifluoromethyl) -2-pyridyl] piperidine (Compound 1-105) Produce

60% sodium hydride (88 mg) was added to a solution of DMF (5 ml) of 4-fluoro-3-hydroxybenzotrifluoride (0.36 g), followed by cooling of chloromethyl methyl ether (0.24 g) with ice. And the mixture was allowed to warm to room temperature and stirred for 5 hours. Water was poured into the mixture and subjected to extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give crude compound (11) (0.45 g), which was used in subsequent steps.

60% sodium hydride (90 mg) was added to a solution of DMF (5 ml) of piperidine (12) (0.49 g) at room temperature. After the mixture was stirred for 10 minutes, a DMF (5 ml) solution of benzotrifluoride (11) was added thereto, then heated to about 100 ° C. and then stirred overnight. After the mixture was cooled to room temperature, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the compound (0.56 g) mentioned as the title compound.

Preparation Example 7

Preparation of 4- [2-hydroxy-4- (trifluoromethyl) phenoxy] -1- [5- (trifluoromethyl) -2-pyridyl] piperidine (Compound 1-4)

A 10% hydrochloric acid solution (5 ml) was added to a THF (5 ml) solution of piperidine (Compound 1-105, 0.38 g) prepared in Preparation Example 6 at room temperature. After the mixture was stirred for 2 hours, 10% hydrochloric acid solution (5 ml) was added and stirred overnight. Water was poured into the mixture and extracted with ethyl acetate. The organic layer was washed with saturated sodium bicarbonate and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give the abovementioned title compound (0.31 g).

Viscous oil

Preparation Example 8

Preparation of 4- [2-acetoxy-4- (trifluoromethyl) phenoxy] -1- [5- (trifluoromethyl) -2-pyridyl] piperidine (Compound 1-167)

Acetyl chloride (36 mg) was added to an acetonitrile (5 ml) solution of piperidine (Compound 1-4, 0.17 g) and triethylamine (50 mg) prepared in Preparation Example 7 while cooling with ice. The mixture was warmed to room temperature, stirred for 3 hours, poured into water and then subjected to extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. Its solvent was evaporated under reduced pressure to give the above-mentioned title compound (0.22 g).

Preparation Example 9

Preparation of 3- [4- (trifluoromethyl) phenoxy] -1- [5- (trifluoromethyl) -2-pyridyl] pyrrolidine (Compound 8-63)

The title compound (0.32 g) mentioned above was prepared using pyrrolidinol (13) (0.35 g) and 4-trifluoromethylphenol (0.16 g) in the same manner as in Example 1. Compound (13) was produced by the same method as the compound (10) in Production Example 1.

Preparation Example 10

2-methyl-4- [2-propoxy-4- (trifluoromethyl) phenoxy] -1- [5- (trifluoromethyl) -2-pyridyl] piperidine (Compound 1-93) Manufacture

Step 1

Preparation of 1-benzyloxycarbonyl-2-methyl-4-piperidinol (14)

The following reaction is described in Tetrahedron Lett. 1986, 27, 4549].

Methyl magnesium bromide (3.0 M, ether solution, 7.6 ml) was added dropwise to a THF (25 ml) solution of 4-methoxypyridine (2.60 g) while maintaining the temperature between -30 ° C and -20 ° C. After stirring the mixture for 10 minutes, benzyl chloroformate (3.90 g) was added dropwise while maintaining the temperature at -30 ° C to -20 ° C. The mixture was stirred for 30 minutes and then warmed to room temperature. 10% hydrochloric acid was added to the mixture, which was then subjected to extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give an oily substance (5.34 g), which was subsequently used directly in a multisystem.

The following reactions are described in J. Org. Chem., 2001, 66, 2181].

After dissolving the oily substance in acetic acid (150 ml), zinc (21.4 g) was added at room temperature. Its suspension was heated to reflux for 6 hours. After cooling the mixture, it was filtered through a pad of CELITE and the filtrate was evaporated under reduced pressure. Water was added to its residue, then neutralized with sodium hydroxide and then subjected to extraction with ethyl acetate. The organic layer was washed with brine and then dried over magnesium sulfate. Its solvent was evaporated under reduced pressure to give an oily substance (5.01 g). To the ethanol (25 ml) solution of the oily substance (2.47 g) was added sodium borohydride (0.38 g) at room temperature and the mixture was stirred for 1 hour. The mixture was concentrated under reduced pressure, water was added and subjected to extraction with ethyl acetate. The organic layer was washed with brine and then dried over magnesium sulfate. The solvent was evaporated under reduced pressure to give crude compound (14) (2.39 g).

Step 2

Preparation of 1-benzyloxycarbonyl-2-methyl-4- [2-propoxy-4- (trifluoromethyl) phenoxy] piperidine

60% sodium hydride (0.42 g) was added to the DMF (25 ml) solution of compound (14) at room temperature. The mixture was stirred for 30 minutes, after which 4-fluoro-3-propoxy benzotrifluoride (2.13 g) was added, followed by heating at 100 ° C. overnight. After the mixture was cooled to room temperature, water was poured and then subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to give compound (15) (1.02 g).

Step 3

Preparation of 2-methyl-4- [2-propoxy-4- (trifluoromethyl) phenoxy-1- [5- (trifluoromethyl) -2-pyridyl] piperidine

5% palladium-carbon (0.20 g) was added to an ethanol (25 ml) solution of compound (15). The suspension was heated at 80 ° C. for 8 hours in a hydrogen atmosphere. After cooling the mixture, it was filtered through a pad of CELITE. The filtrate was evaporated under reduced pressure to give crude compound (16) (0.70 g).

2-chloro-5- (trifluoromethyl) pyridine (4.0 g) and potassium carbonate (1.53 g) are added to the acetonitrile (15 ml) solution of the piperidine and the mixture is heated for 3 days at reflux. did. After cooling the mixture, water was poured and then subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (30 mg).

Viscous oil

Preparation Example 11

3α- [2-methoxy-4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane (compound 2-77) Preparation

Step 1

Preparation of 3α-hydroxy-8-azabicyclo [3.2.1] octane acetic acid (18)

2,2,2-trichloroethyl chloroformate ester (23.3 g) is added to a benzene (150 ml) suspension of tropin (14.1 g) and potassium carbonate (1.4 g) at room temperature and the mixture thereof for 3.5 hours Heated to reflux. After the mixture was cooled to room temperature, water was poured and then subjected to extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. Its solvent was evaporated under reduced pressure to give an oily carbonate (17) (30.08 g) which was used directly in the next step. Zinc powder (65 g) was added to the acetic acid (250 ml) solution of the carbonate (17). The mixture was stirred for 5 minutes and then filtered through a pad of CELITE. The filtrate was evaporated under reduced pressure to give crude compound (18) (15.5 g).

Step 2

Preparation of 3α-hydroxy-8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane (19)

A suspension of acetonitrile (150 ml) of crude compound (18) (5.64 g), potassium carbonate (41.5 g) and 2-chloro-5-trifluoromethyl pyridine (8.2 g) was heated to reflux for 3.5 hours. After cooling the mixture to room temperature, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. Its solvent was evaporated under reduced pressure to give compound (19) (3.5 g) in crystalline form.

Step 3

Preparation of 3α- [2-methoxy-4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane

60% sodium hydride (35 mg) was added to a solution of DMF (3 ml) of 4-fluoro-3-hydroxybenzotrifluoride (0.17 g) while cooling with ice. The mixture was stirred for 20 minutes, after which iodomethane (0.11 g) was added and then heated to 60 ° C. with stirring for 40 minutes. After the mixture was cooled to room temperature, compound (19) (0.22 g) and 60% sodium hydride (35 mg) were added at room temperature, and then heated at 100 ° C. overnight. After the mixture was cooled to room temperature, iced water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the title compound (0.18 g) mentioned above.

Viscous oil

Preparation Example 12

3α- [2-propoxy-4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane (compound 2-82) Preparation

Step 1

Preparation of 8-methyl-3α- [2-propoxy-4- (trifluoromethyl) phenoxy] -8-azabicyclo [3.2.1] -octane (20)

60% sodium hydride (0.44 g) was added to the 4-fluoro-3-hydroxybenzotrifluoride (1.8 g) DMF (15 ml) solution while cooling with ice. The mixture was stirred for 20 minutes, after which a DMF (3 ml) solution of 1-iodopropane (1.7 g) was added and then further stirred for 4 hours. Tropin (1.42 g) and 60% sodium hydride (0.43 g) were added to the mixture at room temperature and heated with stirring at 100 ° C. overnight. After the mixture was cooled to room temperature, iced water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to give an oily compound (20) (1.1 g).

Step 2

Preparation of 3α- [2-propoxy-4- (trifluoromethyl) phenoxy] -8-azabicyclo [3.2.1] octane hydrochloride (22)

A solution of methylene chloride (4 ml) of 1-chloroethyl chloroformate (0.83 g) was added to a solution of methylene chloride (6 ml) of compound (20) (1.0 g) at room temperature, and the mixture was heated to reflux overnight. . The mixture was diluted with methyl chloride, washed with saturated bicarbonate solution and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give crude carbonate (21) which was used directly for the subsequent reaction.

Methanol (6 ml) was added to compound (21) and heated to reflux for 2.5 hours. The mixture was concentrated under reduced pressure to obtain crude 22, which was used directly for the next reaction.

¹ H NMR of compound (22) without salt (CDCl ₃ )

Step 3

Of 3α- [2-propoxy-4- (trifluoromethyl) -phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane Produce

The ethanol (10 ml) solution of crude (22), triethylamine (1.18 g) and 2-chloro-5-trifluoromethyl pyridine (0.53 g) was refluxed while heating overnight. To the mixture, triethylamine (3 g), 2-chloro-5-trifluoromethyl pyridine (1.6 g) and ethanol (10 ml) were added, heated overnight and further refluxed. After the mixture was cooled to room temperature, iced water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (0.31 g).

Preparation Example 13

8β- [2-propoxy-4- (trifluoromethyl) -phenoxy] -3- [5- (trifluoromethyl) -2-pyridyl] -3-azabicyclo [3.2.1] octane ( Preparation of Compound 5-97)

Step 1

Preparation of N-benzyl-8β- [2-propoxy-4- (trifluoromethyl) -phenoxy] -3-azabicyclo [3.2.1] octane (25)

N-benzyl-3-azabicyclo [3.2.1] octane-8β-ol (24), see J. Benz. Med. Chem. 2003, 46, 1456-1464].

60% sodium hydride (0.12 g) was added to a solution of DMF (4 ml) of 4-fluoro-3-hydroxybenzotrifluoride (0.50 g) while cooling on ice. After the mixture was stirred at room temperature for 30 minutes, 1-iodopropane (0.51 g) was added thereto. The mixture was heated to 90 ° C. and then stirred for 30 minutes. A solution of Compound (24) (0.41 g) and DMF (4 ml) of 60% sodium hydride (0.09 g) was added at room temperature, followed by stirring for 15 minutes, which was heated to 100 ° C. and then stirred for 2 hours. . After the mixture was cooled to room temperature, water was poured and extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to give an oily substance (25) (0.75 g).

Step 2

Preparation of 8β- [2-propoxy-4- (trifluoromethyl) phenoxy] -3- [5- (trifluoromethyl) -2-pyridyl] -3-azabicyclo [3.2.1] octane

10% palladium-carbon (0.13 g) was added to an ethanol (20 ml) solution of compound (25) (0.66 g). The suspension was stirred overnight at room temperature under hydrogen atmosphere. The mixture was filtered through a pad of CELITE, and then the filtrate was evaporated under reduced pressure to give crude compound (26) (0.55 g).

2-chloro-5- (trifluoromethyl) pyridine (0.57 g) and sodium carbonate (0.66 g) were added to an acetonitrile (12 ml) solution of crude compound (26) (0.55 g), and then the mixture was 22 Heated to reflux for an hour. After cooling the mixture, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (0.26 g).

Preparation Example 14

3α- [2-nitro-4- (trifluoromethyl) phenoxy] -8 [5- (trifluoromethyl-2-pyridyl] -8-azabicyclo [3.2.1] octane (Compound 2-35 Manufacture of

60% sodium hydride (0.81 g) was added to a solution of DMF (50 ml) of compound (19) (5 g) prepared in step 2 of Preparation Example 11 while cooling with ice. After stirring the mixture for 30 minutes at room temperature, 4-fluoro-3-nitrobenzotrifluoride (3.84 g) was added. The mixture was stirred for 1 hour at room temperature, then heated to 100 ° C. and then stirred overnight. The mixture was cooled to room temperature and then poured into ice water and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (4.95 g).

Viscous oil

Example 15

3α- [2-amino-4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane (Compound 2 -158)

10% palladium-carbon (0.21 g) and ammonium formate (1.43 g) were added to a methanol (24 ml) solution of compound 2-35 (2.14 g) prepared in Example 14. The mixture was stirred for 1 hour at room temperature. After the mixture was filtered through a pad of CELITE, the filtrate was concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (1.86 g).

Preparation Example 16

3α- [2-allyl-4- (trifluoro) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane (Compound 2- 62) Preparation

The following reactions are described in J. Org. Chem., 2002, 67, 6376-6381.

Compound 2-158 (0.5 g) prepared in Example 15 was slowly added to a solution of acetonitrile (7.5 ml) of t-butyl nitrite (0.18 g) and allyl bromide (2.1 g) at room temperature under a nitrogen atmosphere. The mixture was stirred at rt for 3 h, then water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (76 ml).

Viscous oil

Example 17

9β- [2-methoxymethoxy-4- (trifluoromethyl) phenoxy] -3- [5- (trifluoromethyl) -2-pyridyl] -3-azabicyclo [3.3.1] nonane Preparation of (Compound 7-100)

Step 1

Preparation of N-benzyl-3-azabicyclo [3.3.1] nonan-9-ol (29)

N-benzyl-3-azabicyclo [3.3.1] nonan-9-one (28), see J. Chem. Med. Chem. 1994, 37, 2831-2841]. Sodium borohydride (1.49 g) was added to the MeOH (80 ml) solution of (28) (6.75 g) while cooling with ice. After stirring the mixture for 1 hour while cooling with ice, the solvent was evaporated under reduced pressure. Water was added to its residue and subjected to extraction with methylene chloride, and then the organic layer thereof was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give crude compound (29) (6.52 g).

Step 2

Preparation of 9- [2-methoxymethoxy-4- (trifluoromethyl) phenoxy] -3-benzyl-3-azabicyclo [3.3.1] nonane (30), (31)

60% sodium hydride (1.77 g) was added to the DMF (75 ml) solution of 4-fluoro-3-hydroxybenzotrifluoride (7.49 g) while cooling with ice. The mixture was stirred for 30 minutes at room temperature, then cooled with ice and chloromethyl methyl ether (3.57 g) was added thereto. The mixture was warmed to room temperature, then stirred for 30 minutes, further heated to 80 ° C. and then stirred for 30 minutes. Compound (29) (6.4 g) and 60% sodium hydride (1.33 g) were added to the mixture at room temperature, followed by stirring for 30 minutes, heating to 100 ° C., and stirring for 3 hours. After the mixture was cooled to room temperature, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to give compound (30) (6.3 g) and compound (31) (4.25 g).

(0.56 g) was obtained.

Compound (30): Viscous Oil

Compound (31): Viscous Oil

Step 3

9β- [2-methoxymethoxy-4- (trifluoromethyl) phenoxy] -3- [5- (trifluoromethyl) -2-pyridyl] -3-azabicyclo [3.3.1] nonane Preparation of (Compound 7-100)

10% palladium-carbon (1.22 g) was added to an ethanol (180 ml) solution of compound (30) (6.11 g). The suspension was stirred for 1 h at room temperature under hydrogen atmosphere, then heated to 80 ° C. and then for 7 h. The mixture was cooled to room temperature, then filtered through a pad of CELITE and the filtrate was evaporated under reduced pressure to give crude 32 (4.54 g).

2-Chloro-5- (trifluoromethyl) pyridine (11.92 g) and calcium carbonate (10.9 g) were added to an acetonitrile (180 ml) solution of compound (32) (4.54 g), and then heated to reflux overnight. did. After cooling the mixture, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (2.61 g).

Viscous oil

Example 18

9β- [2-hydroxy-4- (trifluoromethyl) phenoxy] -3- [5- (trifluoromethyl) -2-pyridyl] -3-azabicyclo [3.3.1] nonane (compound 7.4) Manufacturing

The title compound (2.12 g) mentioned above was prepared in a similar manner to Example 7 using compound 7-100 (2.54 g) prepared in Example 17.

Preparation Example 19

9β- [2-propoxy-4- (trifluoromethyl) phenoxy] -3- [5- (trifluoromethyl) -2-pyridyl] -3-azabicyclo [3.3.1] nonane (compound 7-82)

While cooling with ice, 60% sodium hydride (0.03 g) was added to a DMF (15 ml) solution of compound 7-4 (0.3 g) prepared in Example 18. The mixture was stirred for 30 minutes at room temperature, then 1-iodopropane (0.13 g) was added while cooling with ice and stirred at room temperature for 30 minutes. Water was poured into the mixture and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (0.27 g).

Viscous oil

Example 20

3α- [2-propoxy-4- (trifluoromethyl) phenoxy] -8-oxy-8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1 ] Octane (compound 2-84)

m-chloroperbenzoic acid (purity 65%, 0.28 g) was added to the methylene chloride (5 ml) solution (Compound 2-82) (0.48 g) prepared in Preparation Example 12. After refluxing with heating for 2 hours, the mixture was washed sequentially with saturated sodium sulfate solution, potassium carbonate solution and saturated brine. After drying over anhydrous magnesium sulfate, it was filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (0.28 g).

Example 21

3α- [2-propoxy-4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl-1-oxy] -8-azabicyclo [3.2.1 ] Octane (compound 2-83)

Pyridine N-oxide (33) is described in J. Heterocycle. Chem. 1976, 13, 41-42]. Pyridine-N-oxide 33 (0.385 g) and potassium carbonate (0.82 g) are added to the acetonitrile (6 ml) suspension 22 (0.65 g) prepared in Example 13, and the mixture is added for 8 hours. Heated to reflux. After cooling the mixture was poured water and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give the above-mentioned title compound (0.88 g).

Example 22

cis-3-methyl-4- [2-propoxy-4- (trifluoromethyl) phenoxy] -1- [5- (trifluoromethyl) -2-pyridyl] piperidine (Compound 1- 97) manufacturing

Step 1

cis-3-methyl-1- [5- (trifluoromethyl) -2-pyridyl] -4-piperidinol (37) and trans-3-methyl-1- [5- (trifluoromethyl) Preparation of 2-pyridyl] -4-piperidinol (38)

N-benzyl-3-methyl-4-piperidinone (34) is a known compound described in CAS. No. [34737-89-9] and is available from commercially available products. Sodium borosilicate (0.47 g) was added to an EtOH (40 ml) solution of compound (34) (2.53 g) while cooling with ice. The mixture was stirred for 2 h at rt, then cooled with ice and neutralized with 10% hydrochloric acid. After the mixture was extracted with methylene chloride, its organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give crude 35 (2.27 g), which was used for subsequent reaction.

20% carbon palladium hydroxide (0.2 g) was added to a methanol (30 ml) solution of crude 35 (1.82 g). The suspension was heated at 70 ° C. under hydrogen atmosphere and then stirred all day. The mixture was cooled to room temperature and then filtered through a pad of CELITE. 20% palladium carbon hydroxide (0.9 g) was added to the filtrate, and it heated to 70 degreeC, and stirred overnight. The mixture was cooled to room temperature and then filtered through a pad of CELITE. The filtrate was evaporated under reduced pressure to give crude 36 (1.22 g), which was used for the next step.

2-chloro-5- (trifluoromethyl) pyridine (2.3 g) and potassium carbonate (4.4 g) are added to an acetonitrile (50 ml) solution of crude compound (36) (1.22 g) and heated overnight Refluxed. After cooling the mixture, it was poured water and then subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compounds (37) (0.15 g) and (38) (0.55 g).

(37): yellow oily substance

(38): yellow oily substance

Step 2

cis-3-methyl-4- [2-propoxy-4- (trifluoromethyl) phenoxy] -1- [5- (trifluoromethyl) -2-pyridyl] -2-piperidyl] Preparation of Piperidine (Compound 1-97)

60% sodium hydride (0.023 g) was added to a DMF (4 ml) solution of compound (38) (0.15 g) at room temperature. After heating the mixture to 70 ° C., 4-fluoro-3-propoxybenzotrifluoride (0.14 g) was added, followed by heating to 100 ° C. overnight. After cooling the mixture to room temperature, water was poured and then subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. After the residue was purified by column chromatography, the title compound mentioned above was obtained (0.18 g).

Preparation Example 23

3α- [2-butyl-4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane (Compound 2 -187)

Step 1

3α- {2-([1,3] dioxolan-yl) -4- (trifluoromethyl) phenoxy} -8- [5- (trifluoromethyl) -2-pyridyl] -1-8 Preparation of -azabicyclo [3.2.1] -octane (Compound 2-169)

A benzene (50 ml) solution of 2-fluoro-5- (trifluoromethyl) benzaldehyde (5.00 g), ethylene glycol (1.78 g) and p-toluene sulfonate monohydrate (0.49 g) was heated to reflux overnight. did. After the mixture was cooled to room temperature, water was poured and then subjected to extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and the solution was evaporated to give crude compound (39) (5.81 g).

60% sodium hydride (0.50 g) was added to the solution of DMF (20 ml) of crude (39) (2.00 g) and compound (19) (2.30 g) at 80 ° C. in five portions. The mixture was stirred directly at 80 ° C. for 1 hour. After cooling to room temperature, ice water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (3.24 g).

Step 2

3α- [2-formyl-4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane (41 Manufacture of

6 N hydrochloric acid (100 ml) was added to a THF (100 ml) solution of compound (40) (3.24 g) while cooling with ice. The mixture was warmed to room temperature and then stirred for 2 hours. Water was poured into the mixture, which was then subjected to extraction with ethyl acetate. The organic layer was washed with 10% aqueous sodium carbonate solution and brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (2.95 g).

Step 3

3α- [2- (1-hydroxybutyl) -4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2. 1] Preparation of Octane 42

THF solution (1.02 mol / l) (6.06 ml) of n-propyl magnesium bromide was dropped into THF solution of compound (41) (1.83 g) at 0 ° C. under nitrogen atmosphere, then warmed to room temperature and stirred for 2 hours. did. The mixture was poured into saturated aqueous ammonium chloride solution and subjected to extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (42) (0.96 g).

Step 4

3α- [2- (buten-1-yl) -4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2. 1] Manufacture of Octane 43

A toluene (4 ml) solution of compound (42) (0.40 g) and p-toluene sulfonate monohydrate (0.14 g) was heated to reflux overnight. After the mixture was cooled to room temperature, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (43) (0.37 g).

Step 5

Preparation of 3α- [2-butyl-4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane

5% palladium-carbon (0.04 g) was added to an ethanol (6 ml) solution of compound (43) (0.22 g). The suspension was stirred overnight at room temperature under hydrogen atmosphere. Its mixture was filtered through a pad of CELITE and its filtrate was evaporated under reduced pressure. Its residue was purified by column chromatography to give the title compound (0.18 g) mentioned above.

Preparation Example 24

Preparation of 4- [2-propoxy-4- (trifluoromethyl) phenylsulfanyl] -1- [5- (trifluoromethyl) -2-pyridyl] -piperidine (Compound 9-94)

Step 1

Preparation of 1-benzyloxy-2-propoxy-4- (trifluoromethyl) benzene (44)

60% sodium hydride (0.44 g) was added to the DMF (20 ml) solution of 4-fluoro-3-hydroxybenzotrifluoride (1.80 g), cooled on ice, and the resulting mixture was allowed to warm to room temperature. Then, it was stirred for 30 minutes and a solution of DMF (5 ml) of 1-iodopropane (1.87 g) was added. The mixture was heated to 80 ° C. and then stirred for 30 minutes. After the mixture was cooled to room temperature, benzyl alcohol (2.16 g) and 60% sodium hydride were added, heated to 80 ° C. and stirred for 30 minutes. After the mixture was cooled to room temperature, iced water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (44) (2.95 g).

Step 2

Preparation of 2-propoxy-4- (trifluoromethyl) benzenethiol (46)

After adding 10% palladium-carbon (0.59 g) to the ethanol solution of compound (44) (2.95 g), the suspension was stirred overnight at room temperature under hydrogen atmosphere. After the mixture was filtered through a pad of CELITE, the filtrate was evaporated under reduced pressure to give crude compound 45 (2.01 g).

The abovementioned title compound (46) (1.82 g) is described in J. Med. Chem., 2002, 45, 3972-3983, according to the method described in crude compound (45) (2.01 g).

Step 3

Preparation of 4-bromo-1- [5- (trifluoromethyl) -2-pyridyl] piperidine (48)

Triethylamine (0.45 g) and methane sulfonyl chloride (0.51 g) were cooled in ice and added to an acetonitrile (10 ml) solution of compound (12) (1.00 g) and the mixture was allowed to warm to room temperature. After stirring for 30 minutes, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give crude 47 (1.32 g).

Lithium bromide (1.06 g) was added to a DMF (13 ml) solution of crude compound (47) (1.32 g), and the mixture was stirred at 80 ° C. for 1 hour. After cooling the mixture, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (48) (0.74 g).

Step 4

Preparation of 4- [2-propoxy-4- (trifluoromethyl) phenylsulfanyl] -1- [5- (trifluoromethyl) -2-pyridyl] piperidine

60% sodium hydride was added to a solution of DMF (7 ml) of compound (46) (0.62 g) while cooling with ice, then warmed to room temperature, followed by stirring for 30 minutes. Compound (48) (0.74 g) was added to the mixture, which was then heated to 100 ° C and stirred for 1 hour. After cooling the mixture was poured water and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the title compound mole (0.09 g) mentioned above.

Viscous oil

Preparation Example 25

Of 3α- [2-propoxy-4- (trifluoromethyl) phenylsulfanyl] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane Produce

Step 1

Preparation of 3β-acetoxy-8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane (50)

Triethylamine (1.12 g) and methane sulfonylchloride (1.26 g) were added to a solution of methylene chloride (20 ml) of compound (19) (2.00 g) while cooling with ice, followed by stirring for 30 minutes. Water was poured into the mixture and subjected to extraction with ethyl acetate. Water was poured into the mixture and subjected to extraction with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give crude compound (49) (2.29 g).

Cesium acetate (1.88 g) was added to a DMF (35 ml) solution of crude compound (49) (2.29 g), then heated to 100 ° C. and stirred overnight. After the mixture was cooled to room temperature, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (50) (1.15 g).

Step 2

Of 3α- [2-propoxy-4- (trifluoromethyl) phenoxysulfanyl] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane Produce

A methanol solution (0.07 g) of 28% sodium methoxide was added to a methanol (25 ml) solution of compound (50) (1.15 g), and then the mixture was stirred at reflux for 2 hours. After cooling it, methanol was evaporated under reduced pressure, and water was poured into it, followed by extraction with ethyl acetate. The organic layer was washed with brine and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give crude compound 51 (1.00 g).

Triphenylphosphine (1.93 g) and diisopropyl azodicarboxylate (1.49 g) were added to a toluene (10 ml) solution of crude compound (51) (1.00 g) and compound (46) (0.87 g). After stirring overnight at room temperature. Water was poured into the mixture and subjected to extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (0.39 g).

Preparation Example 26

3α- [2-isopropylideneaminooxy-4- (trifluoromethyl) phenol group] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] Preparation of Octane (Compound 2-212)

Step 1

3α- [2-methoxymethoxy-4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane Manufacture of 52

60% sodium hydride (0.59 g) was added to a solution of DMF (30 ml) of 4-fluoro-3-hydroxybenzotrifluoride (2.48 g) while cooling with ice. The mixture was stirred at rt for 30 min, then chloromethyl methyl ether (1.18 g) was added dropwise while cooling with ice. The mixture was warmed to room temperature and stirred for 30 minutes, then heated to 80 ° C. and then stirred for 30 minutes. Compound (19) (2.50 g) and 60% sodium hydride (0.55 g) were added to the mixture at room temperature and stirred for 30 minutes, then heated to 100 ° C. and then stirred for 2 hours. After the mixture was cooled to room temperature, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (52) (3.98 g).

Step 2

3α- [2-hydroxy-4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane (53 Manufacture of

The title compound (53) (3.61 g) mentioned above was prepared using compound (52) (3.98 g) in a similar manner as in Example 7.

Step 3

3α- [2-isopropylideneamioxy-4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1 ] Manufacture of Octane

90.54 g) of compound (54) were synthesized using compound (53) (1.00 g) according to the method described in Japanese Patent Publication No. 2001-81071.

Acetone (1 ml) and concentrated hydrochloric acid (0.03 g) were added to an ethanol (2 ml) solution of compound (54) (0.25 g), followed by stirring at room temperature for 1 hour. Water was poured into the mixture, which was then extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (0.20 g).

Preparation Example 27

3α- [2- (2-methylpropeneoxy) -4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2 .1] octane (compound 2-245)

Step 1

3α- [2- (2-methylallyloxy) -4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2. 1] Manufacture of octane 55

60% sodium hydride (0.05 g) was added to a solution of DMF (5 ml) of compound (53) (0.50 g) while cooling with ice. The mixture is added at room temperature for 30 minutes, then methyl chloride (0.14 g) and sodium iodide (0.23 g) are added while cooling with ice, the mixture is allowed to warm to room temperature, then stirred for 30 minutes, then 80 ° C. After heating to, it was further stirred for 1 hour. After the mixture was cooled to room temperature, water was added and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (55) (0.48 g).

Step 2

3α- [2- (2-methylpropenyloxy) -4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2 .1] octane production

t-butoxy potassium (0.11 g) was added to a DMSO solution of compound (55) (0.42 g), and then stirred at 100 ° C. for 5 hours. After the mixture was cooled to room temperature, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the title compound (0.19 g) mentioned above.

Preparation Example 28

5-trifluoromethyl-2- {3α- [5- (trifluoromethyl) pyridyl] -8-azabicyclo [3.2.1] octa-3-yloxy} benzoic acid furan 2-yl ester (Compound 2 -244)

Step 1

3α- [2-cyano-4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabicyclo [3.2.1] octane (56 Manufacture of

60% sodium hydride (0.71 g) was added to a solution of DMF (30 ml) of compound (19) (3.69 g) while cooling with ice. The mixture was stirred at rt for 30 min and then 4-chloro-3-cyclobenzotrifluoride (2.78 g) was added. The mixture was stirred at rt for 30 min, then further heated at 100 ° C. and stirred for 4 h. After the mixture was cooled to room temperature, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (56) (4.24 g).

Step 2

5-trifluoromethyl-2- {3α- [5- (trifluoromethyl) pyridyl] -8-azabicyclo [3.2.1] octa-3-yloxy} benzoic acid furan 2-yl ester

Potassium hydride (5.38 g) was added to a ethanol (100 ml) solution of compound (56) (4.24 g) and stirred at reflux overnight. After the mixture was cooled to room temperature, water was added, then neutralized with hydrochloric acid, and then extracted with acetic acid ester. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The obtained crystals were dissolved in acetic acid (22 ml) and sodium nitrate (0.99 g) and concentrated sulfuric acid (3.59 g) were added gradually while cooling on ice. The mixture was warmed to room temperature and stirred for 5 hours. Ice water was poured into the mixture, which was then subjected to extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give Compound (57) (4.17 g).

The solution prepared by dropping sulfuryl chloride (0.17 g) into THF (2 ml) at 30 DEG C or lower was stirred at room temperature for 10 minutes, and then cooled with ice to give THF of Compound (57) (0.20 g). ml) was added to the solution, followed by further addition of triethylamine (0.22 g). The mixture was warmed to room temperature and then stirred for 30 minutes. Water was poured into the mixture, which was then subjected to extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to give the title compound (72 mg) described above.

Preparation Example 29

3α- [2- (2-methyloxazol-5-yl) -4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabi Preparation of cyclo [3 .2.1] octane (Compound 2-214)

Step 1

3α- [2- (2-methyl [1,3] dioxalan-2-yl) -4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl ] -8-azabicyclo [3.2.1] octane (61) Preparation of

3.0 M methylmagnesium bromide (7.8 ml) was added dropwise to a THF (30 ml) solution of 2-fluoro-5-trifluoromethyl benzaldehyde (3.0 g) at 0 ° C. under a nitrogen atmosphere. The mixture was warmed to room temperature, then stirred for 30 minutes, poured into saturated aqueous ammonium chloride solution and subjected to extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure to give crude compound (58) (3.42 g).

Magnesium dioxide (6.78 g) was added to a chloroform solution of crude compound (58) (3.42 g), and then the suspension was stirred for 2 hours while heating to reflux. The suspension was cooled to room temperature and then filtered through a pad of CELITE. The filtrate was concentrated under a reduced pressure to obtain crude compound (59).

Ethylene glycol (0.66 g) and p-toluene sulfonic acid monohydrate (0.09 g) were added to a benzene (10 ml) solution of crude compound (59) (1.00 g), and stirred for 5 hours while heating to reflux. After the mixture was cooled to room temperature, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and then concentrated under reduced pressure to give crude compound (60) (1.13 g).

60% sodium hydride (0.18 g) was added to a DMF (10 ml) solution of compound (19) (1.02 g) while cooling with ice. The mixture was stirred for 30 minutes at room temperature, then crude compound (60) (1.13 g) was added. The mixture was stirred for 30 minutes at room temperature, then further heated to 100 ° C. and then stirred for 8 hours. After the mixture was cooled to room temperature, water was poured and subjected to extraction with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Its residue was purified by column chromatography to give the above-mentioned title compound (61) (0.55 g).

Step 2

3α- [2- (2-methyloxazol-5-yl) -4- (trifluoromethyl) phenoxy] -8- [5- (trifluoromethyl) -2-pyridyl] -8-azabi Of cyclo [3.2.1] octane

6N hydrochloric acid (21 ml) was added to a THF (21 ml) solution of compound (61) (0.55 g) and stirred at room temperature for 2 hours. Water was added to the mixture, neutralized with 10% aqueous sodium hydroxide solution, and then subjected to extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give Compound (62) (0.46 g).

The abovementioned title compound (0.20 g) is described in J. Heterocyclic Chem., 1998, 35, 1533-1534] was prepared using crude compound (62) (0.30 g).

Specific examples of the present invention including the above-mentioned examples are shown in Tables 1 to 14. The precise scope of the invention is not limited to these examples and descriptions.

The irregular representation used in the table has the following meaning:

Vis: Viscous substance

Amor: Atypical

Me: methyl, Et: ethyl, Pr: propyl, Bu: butyl, Hex: hexyl, Pen: pentyl, i: iso, n: normal, t: tertiary, c: cyclo, Ac: acetyl

TABLE 1

TABLE 2

TABLE 3

TABLE 4

TABLE 5

TABLE 6

TABLE 7

TABLE 8

TABLE 9

TABLE 10

TABLE 11

TABLE 12

TABLE 13

TABLE 14

NMR data

¹ H-NMR (CDCl ₃ )

Compound 1-169

Compound 1-80

Compound 1-143

Compound 1-163

Compound 1-172

Compound 1-69

Compound 1-173

Compound 1-140

Compound 1-74

Compound 1-67

Compound 2-57

Compound 2-58

Compound 2-78

Compound 2-141

Compound 3-62

Compound 2-148

Compound 2-144

Compound 2-115

Compound 2-153

Compound 2-112

Compound 2-161

Compound 2-143

Compound 2-138

Compound 2-101

Compound 5-175

Compound 5-89

Compound 5-90

Compound 5-176

Compound 5-139

Compound 5-123

Compound 5-147

Compound 5-124

Compound 5-132

Compound 5-134

Compound 5-133

Compound 5-163

Compound 5-126

Compound 5-127

Compound 5-128

Compound 5-129

Compound 5-130

Compound 5-114

Compound 5-138

Compound 5-98

Compound 5-202

Compound 6-82

Compound 7-103

Compound 2-130

Compound 1-98

Compound 5-118

Compound 6-4

Compound 2-90

Compound 2-167

Compound 1-95

Compound 5-93

Compound 2-81

Compound 2-67

Compound 5-99

Compound 5-103

Compound 5-101

Compound 5-4

Compound 5-177

Compound 5-75

Compound 5-69

Compound 5-131

Compound 5-137

Compound 5-136

Compound 5-73

Compound 5-229

Compound 9-94

Compound 11-93

Compound 5-246

Compound 5-247 (trans / cis = 59/41)

trans form

cis form

Compound 2-203

Compound 2-224

Compound 2-148

Compound 2-144

Compound 2-115

Compound 2-153

Compound 2-112

Compound 2-161

Compound 2-143

Compound 2-138

Compound 2-101

Compound 5-175

Compound 5-89

Compound 5-90

Compound 5-176

Compound 5-139

Compound 5-123

Compound 5-147

Compound 5-124

Compound 5-132

Compound 5-134

Compound 5-133

Compound 5-203

Compound 5-163

Compound 5-204

Compound 5-126

Compound 5-127

Compound 5-128

Compound 5-129

Compound 5-130

Compound 5-114

Compound 5-138

Compound 5-206

Compound 5-208

Compound 5-207

Compound 5-98

Compound 5-209

Compound 5-104

Compound 5-206

Compound 7-103

Compound 2-130

Compound 1-98

Compound 5-118

Compound 8-4

Compound 2-90

Compound 2-167

Compound 1-95

Compound 5-93

Compound 2-81

Compound 2-67

Compound 5-99

Compound 5-103

Compound 5-101

Formulation example

Insecticides, acaricides

Specific examples of the compositions of the present invention are presented below, but the additives and additive ratios are not limited to these examples and may vary widely. The part shown in the formulation example means a weight part.

Formulation Example 1 Wettable Powder

40 parts of a compound of the present invention

Diatomite Part 53

Higher Alcohol Sulfate Ester Part 4

Alkyl naphthalene sulfonate 3 parts

The above materials were mixed together homogeneously, and then finely ground to prepare a water dispersible powder containing 40% of the active material thereof.

Formulation Example 2 Emulsion Concentrate

30 parts of a compound of the present invention

Xylene Part 33

Dimethylformamide 30 parts

Polyoxyethylene alkylallyl ether 7 part

The materials were mixed and dissolved together to prepare an emulsion containing 30% of the active material.

Formulation Example 3 Dusting Powder

10 parts of a compound of the present invention

Talc 89

Polyoxyethylenealkylallyl ether 1 part

The materials were mixed homogeneously and then ground finely to prepare a dusting powder containing 10% of the active material.

Formulation Example 4 Granules

5 parts of a compound of the present invention

73 parts of clay

Bentonite Part 20

Sodium Dioctylsulfosuccinate 1 part

Sodium phosphate 1 part

The materials were ground and mixed to add water, kneaded together well to granulate, and then dried to prepare granules containing 5% of the active material.

Formulation Example 5 Suspension

10 parts of a compound of the present invention

Sodium Lignin Sulfonate Part 4

Sodium Dodecylbenzenesulfonate 1 part

Xanthan Gum 0.2 part

84.8 parts water

The materials were mixed together and wet granulated until their particle size was less than 1 micron to prepare a suspension comprising the active material in a proportion of 10%.

In the following, the test examples show that the compounds of the present invention are useful as active ingredients of various acaricides.

Test Example 1 Effect on spotted mites

Seventeen, organoresistant tolerant mite adults were inoculated into the first lobe of 3.5-inch potted kidney beans, infected for 7 to 10 days, and then the respective concentrations of the water dispersed powder shown in Formulation Example 1 above. Each liquid diluted with water was sprayed to adjust to 125 ppm according to the formulation of. They were kept in a thermally stable chamber at 25 ° C. for 3 days with humidity of 65%, and adult killing rates were calculated. This test was repeated twice. As a result, the following compounds killed 100% of adults.

Test Example 2 Effect on Tangerine Mite

Ten adult, acaricide-resistant tangerine females were inoculated into tangerine leaves placed on the dish and diluted with water to adjust the concentration of each compound to 31 ppm according to the formulation of the emulsifiable concentrate set forth in Formulation Example 2 above. Was sprayed using a rotary spray tower. They were left for 3 days with a humidity of 65% in a heat setting chamber at 25 ° C., and then removed from the dish to check whether eggs laid for 3 days were grown to adult on day 7. As a result, the following compounds killed 100% of the adults.

Test Example 3 Effect on anarmy worm

Ten foods were prepared by filling plastic test tubes (volume 1.4 ml) with 0.2 ml of commercial artificial feed (Insecta LFS, Nosan Corporation). Each 1% compound solution was prepared using DMSO (containing 0.5% tween 20) and 10 μg of each compound was dropped onto the surface of the food. Two giant worms, each of the second age, were infected with each test tube and sealed with their plastic lid. After standing at 25 ° C. for 5 days, the killing rate and the food consumption rate of the macroworms were examined. The test was repeated twice. As a result, the following compounds eradicated 100% of worms or inhibited their feed consumption to less than 10% compared to the feed consumption of the solvent control region, which shows that the following compounds are effective.

The cyclic amine compound represented by the formula (I) and salts or oxides thereof can exert an excellent effect as an active ingredient of an insecticide or acaricide.

Claims (6)

A compound represented by formula (I) or a salt thereof or an N-oxide: [Formula I]

[In formula, R <^3> , R <^31> , R <^4> , R <^41> , R <^5> , R <^51> , R <^6> , R <^61> and R <^7> respectively independently represent a hydrogen atom, a C _1-6 alkyl group, and a C _1-6 alkoxycarbonyl group. Or a C _1-6 alkoxy group, R ³ and R ⁴ , or R ⁵ and R ⁶ may be combined to form a saturated ring. X represents an oxygen atom, a sulfur atom, a sulfinyl group, or a sulfonyl group. When R ³ and R ⁴ , or R ⁵ and R ⁶ are combined to form a saturated ring, or R ³ and R ⁴ , R ⁵ and R ⁶ are either one to form a saturated ring And when X represents a sulfur atom, a sulfinyl group, or a sulfonyl group, R ¹ is a hydroxyl group, a halogen atom, a cyano group, a nitro group, a formyl group, a C _1-6 alkyl group which may be substituted with G ¹ , a C _2-6 alkenyl group, C _2-6 alkynyl group, C _1-6 Haloalkyl group, C _1-6 haloalkenyl group, C _1-6 alkylcarbonyl group, C _1-6 alkoxy group which may be substituted with G ² , C _1-6 haloalkoxy group, C _2-6 alkenyloxy group, C _{2 -6} haloalkenyloxy group, C _2-6 alkynyloxy group, C _1-6 alkylcarbonyloxy group, C _1-6 alkoxycarbonyloxy group, C _1-6 alkylthiocarbonyloxy group, substituted with G ³ import amino group, C _1-6 alkylthio which may be, C _1-6 halo-alkyl group, C _1-6 alkylsulfinyl group, C _1-6 haloalkylsulfinyl group, C _1-6 alkylsulfonyl, C _{1- 6} haloalkylsulfonyl group, C _1-6 alkylsulfonyloxy group, C _1-6 haloalkylsulfonyloxy group, heterocyclic group which may be substituted with G ⁴ (One or more hetero atoms selected from oxygen atom, nitrogen atom and sulfur atom) 5 or 6 membered heterocyclic group), or It represents any one of substituents represented by the learning:

(Wherein R ⁸ and R ⁹ each independently represent a C _1-6 alkyl group, Y ¹ , Y ² and Y ³ each independently represent an oxygen atom or a sulfur atom, and A may be substituted with G ⁴ ) Heterocyclic group (a 5 or 6 membered heterocyclic group having one or more heteroatoms selected from an oxygen atom and a nitrogen atom), R ¹⁰ represents a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, C _1-6 alkyl C _1-6 alkoxy group, C _1-6 haloalkyl group, or a heterocyclic group which may be substituted with G ⁴ (5 or 6 having one or more heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom) Ring heterocyclic group), R ¹¹ and R ¹² each independently represent a hydrogen atom, a C _1-6 alkyl group, a C _2-6 alkenyl group or a C _2-6 alkynyl group, and R ¹³ and R ¹⁴ each independently A C _1-6 alkyl group, R ¹³ and R ¹⁴ may be bonded together to form a ring}; When either of R ³ and R ⁴ , R ⁵ and R ⁶ becomes one to form a saturated ring, and X represents an oxygen atom, R ¹ is a hydroxyl group, formyl group, C _1-6 alkyl group substituted with G ¹ , C _2-6 alkenyl group, C _2-6 alkynyl group, C _1-6 haloalkenyl group, C _1-6 alkylcarbonyl group , C _1-6 alkoxy group substituted with G ² , C _1-6 haloalkoxy group, C _2-6 alkenyloxy group, C _2-6 haloalkenyloxy group, C _2-6 alkynyloxy group, C _1-6 alkylcarbonyloxy group, C _1-6 alkoxy carbonyloxy group, C _1-6 alkylthio carbonyloxy group, C _1-6 alkylthio import, C _1-6 halo-alkyl group, C _1-6 alkylsulfinyl Nyl group, C _1-6 haloalkylsulfinyl group, C _1-6 alkylsulfonyl group, C _1-6 haloalkylsulfonyl group, C _1-6 alkylsulfonyloxy group, C _1-6 haloalkylsulfonyloxy group, or Represents any one substituent represented by:

Wherein R ⁸ , R ⁹ , Y ¹ , Y ² , Y ³ , A, R ¹¹ , R ¹² , R ¹³ and R ¹⁴ are the same as defined above, respectively; m represents 0 or an integer from 1 to 5, R ² is a heterocyclic group which may be substituted with a halogen atom, a nitro group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _1-6 haloalkyl group, G ⁴ (oxygen atom, nitrogen atom and sulfur atom) 5 or 6 membered heterocyclic group having one or more heteroatoms), or a C _1-6 haloalkoxy group, k represents an integer of 0 or 1 to 4, G ¹ is a hydroxyl group, a C _1-6 alkoxycarbonyl group, a C _1-6 alkoxy group, a C _1-6 alkoxy C _1-6 alkoxy group, a heterocyclic group which may be substituted with G ⁴ (oxygen atom, nitrogen atom and sulfur 5 or 6 membered heterocyclic group having one or more heteroatoms selected from atoms), or a C _3-6 cycloalkyl group, G ² is hydroxyl group, a cyano group, an amino group which may be substituted by G ^4, C _1-6 alkoxy group, C _1-6 alkylthio, C _1-6 alkylsulfonyl, C _1-6 alkoxy groups, C _{A 1-6} alkoxy C _1-6 alkoxy group, a C _3-6 cycloalkyl group, or a C _6-10 aryl group which may be substituted with a halogen atom or a C _1-6 alkyl group, G ³ represents a C _1-6 alkyl group, C _1-6 alkylcarbonyl group or C _1-6 alkylsulfonyl group, G ⁴ represents a C _1-6 alkyl group or C _1-6 alkoxy group, n represents 0 or 1]. The compound of claim 1, wherein the substituted position of R ² is the 5 position of the pyridine ring. 3. The compound of claim 1, wherein at least one substituted position of R ¹ is the 2 position of the benzene ring. Pest control agents comprising a compound represented by the formula (I) or a salt thereof or an N-oxide as an active ingredient: [Formula I]

[Wherein, R ¹ is a hydroxyl group, a halogen atom, a cyano group, a nitro group, a formyl group, a C _1-6 alkyl group, C _2-6 alkenyl group, C _2-6 alkynyl group, which may be substituted with G ¹ , C _1-6 haloalkyl group, C _1-6 haloalkenyl group, C _1-6 alkylcarbonyl group, C _1-6 alkoxy group which may be substituted with G ² , C _1-6 haloalkoxy group, C _2-6 alkenyl jade group, a C _2-6 haloalkenyl group, a C _2-6 alkynyl group, a C _1-6 alkylcarbonyloxy group, C _1-6 alkoxy carbonyloxy group, C _1-6 alkylthio carbonyloxy group, an amino group which may be substituted by G ^3, C _1-6 alkylthio, C _1-6 halo-alkyl group, C _1-6 alkylsulfinyl group, C _1-6 haloalkylsulfinyl group, C _1-6 alkylsulfonyl group , C _1-6 haloalkylsulfonyl group, C _1-6 alkylsulfonyloxy group, C _1-6 haloalkylsulfonyloxy group, heterocyclic group which may be substituted with G ⁴ (selected from oxygen atom, nitrogen atom and sulfur atom) 5 or 6 membered heterocyclic group having one or more heteroatoms), and It refers to any one of substituents represented by the formula:

(Wherein R ⁸ and R ⁹ each independently represent a C _1-6 alkyl group, Y ¹ , Y ² and Y ³ each independently represent an oxygen atom or a sulfur atom, and A may be substituted with G ⁴ ) Heterocyclic group (a 5 or 6 membered heterocyclic group having one or more heteroatoms selected from an oxygen atom and a nitrogen atom), R ¹⁰ represents a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, C _1-6 alkyl C _1-6 alkoxy group, C _1-6 haloalkyl group, or a heterocyclic group which may be substituted with G ⁴ (5 or 6 having one or more heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom) Ring heterocyclic group), R ¹¹ and R ¹² each independently represent a hydrogen atom, a C _1-6 alkyl group, a C _2-6 alkenyl group or a C _2-6 alkynyl group, and R ¹³ and R ¹⁴ each independently A C _1-6 alkyl group, R ¹³ and R ¹⁴ may be bonded together to form a ring}; m represents 0 or an integer from 1 to 5, R ² is a heterocyclic group which may be substituted with a halogen atom, a nitro group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _1-6 haloalkyl group, G ⁴ (oxygen atom, nitrogen atom and sulfur atom) 5 or 6 membered heterocyclic group having one or more heteroatoms), or a C _1-6 haloalkoxy group, k represents an integer of 0 or 1 to 4, R ³ , R ³¹ , R ⁴ , R ⁴¹ , R ⁵ , R ⁵¹ , R ⁶ , R ⁶¹ and R ⁷ are each independently a hydrogen atom, a C _1-6 alkyl group, a C _1-6 alkoxycarbonyl group or C _1-6 An alkoxy group, R ³ and R ⁴ may be taken together or R ⁵ and R ⁶ may be bonded together to form a saturated ring, X represents an oxygen atom, a sulfur atom, a sulfinyl group or a sulfonyl group, G ¹ is a hydroxyl group, a C _1-6 alkoxycarbonyl group, a C _1-6 alkoxy group, a C _1-6 alkoxy C _1-6 alkoxy group, a heterocyclic group which may be substituted with G ⁴ (oxygen atom, nitrogen atom and sulfur 5 or 6 membered heterocyclic group having one or more heteroatoms selected from atoms), or a C _3-6 cycloalkyl group, G ² is hydroxyl group, a cyano group, an amino group which may be substituted by G ^4, C _1-6 alkoxy group, C _1-6 alkylthio, C _1-6 alkylsulfonyl, C _1-6 alkoxy groups, C _{A 1-6} alkoxy C _1-6 alkoxy group, a C _3-6 cycloalkyl group, or a C _6-10 aryl group which may be substituted with a halogen atom or a C _1-6 alkyl group, G ³ represents a C _1-6 alkyl group, C _1-6 alkylcarbonyl group or C _1-6 alkylsulfonyl group, G ⁴ represents a C _1-6 alkyl group or C _1-6 alkoxy group, n represents 0 or 1]. Insecticides comprising as an active ingredient a compound represented by the formula (I) or a salt thereof or N-oxide: [Formula I]

[Wherein, R ¹ is a hydroxyl group, a halogen atom, a cyano group, a nitro group, a formyl group, a C _1-6 alkyl group, C _2-6 alkenyl group, C _2-6 alkynyl group, which may be substituted with G ¹ , C _1-6 haloalkyl group, C _1-6 haloalkenyl group, C _1-6 alkylcarbonyl group, C _1-6 alkoxy group which may be substituted with G ² , C _1-6 haloalkoxy group, C _2-6 alkenyl jade group, a C _2-6 haloalkenyl group, a C _2-6 alkynyl group, a C _1-6 alkylcarbonyloxy group, C _1-6 alkoxy carbonyloxy group, C _1-6 alkylthio carbonyloxy group, an amino group which may be substituted by G ^3, C _1-6 alkylthio, C _1-6 halo-alkyl group, C _1-6 alkylsulfinyl group, C _1-6 haloalkylsulfinyl group, C _1-6 alkylsulfonyl group , C _1-6 haloalkylsulfonyl group, C _1-6 alkylsulfonyloxy group, C _1-6 haloalkylsulfonyloxy group, heterocyclic group which may be substituted with G ⁴ (selected from oxygen atom, nitrogen atom and sulfur atom) 5 or 6 membered heterocyclic group having one or more heteroatoms), and It refers to any one of substituents represented by the formula:

(Wherein R ⁸ and R ⁹ each independently represent a C _1-6 alkyl group, Y ¹ , Y ² and Y ³ each independently represent an oxygen atom or a sulfur atom, and A may be substituted with G ⁴ ) Heterocyclic group (a 5 or 6 membered heterocyclic group having one or more heteroatoms selected from an oxygen atom and a nitrogen atom), R ¹⁰ represents a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, C _1-6 alkyl C _1-6 alkoxy group, C _1-6 haloalkyl group, or a heterocyclic group which may be substituted with G ⁴ (5 or 6 having one or more heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom) Ring heterocyclic group), R ¹¹ and R ¹² each independently represent a hydrogen atom, a C _1-6 alkyl group, a C _2-6 alkenyl group or a C _2-6 alkynyl group, and R ¹³ and R ¹⁴ each independently A C _1-6 alkyl group, R ¹³ and R ¹⁴ may be bonded together to form a ring}; m represents 0 or an integer from 1 to 5, R ² is a heterocyclic group which may be substituted with a halogen atom, a nitro group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _1-6 haloalkyl group, G ⁴ (oxygen atom, nitrogen atom and sulfur atom) 5 or 6 membered heterocyclic group having one or more heteroatoms), or a C _1-6 haloalkoxy group, k represents an integer of 0 or 1 to 4, R ³ , R ³¹ , R ⁴ , R ⁴¹ , R ⁵ , R ⁵¹ , R ⁶ , R ⁶¹ and R ⁷ are each independently a hydrogen atom, a C _1-6 alkyl group, a C _1-6 alkoxycarbonyl group or C _1-6 An alkoxy group, R ³ and R ⁴ may be taken together or R ⁵ and R ⁶ may be bonded together to form a saturated ring, X represents an oxygen atom, a sulfur atom, a sulfinyl group or a sulfonyl group, G ¹ is a hydroxyl group, a C _1-6 alkoxycarbonyl group, a C _1-6 alkoxy group, a C _1-6 alkoxy C _1-6 alkoxy group, a heterocyclic group which may be substituted with G ⁴ (oxygen atom, nitrogen atom and sulfur 5 or 6 membered heterocyclic group having one or more heteroatoms selected from atoms), or a C _3-6 cycloalkyl group, G ² is hydroxyl group, a cyano group, an amino group which may be substituted by G ^4, C _1-6 alkoxy group, C _1-6 alkylthio, C _1-6 alkylsulfonyl, C _1-6 alkoxy groups, C _{A 1-6} alkoxy C _1-6 alkoxy group, a C _3-6 cycloalkyl group, or a C _6-10 aryl group which may be substituted with a halogen atom or a C _1-6 alkyl group, G ³ represents a C _1-6 alkyl group, C _1-6 alkylcarbonyl group or C _1-6 alkylsulfonyl group, G ⁴ represents a C _1-6 alkyl group or C _1-6 alkoxy group, n represents 0 or 1]. Acaricides comprising as an active ingredient a compound represented by formula (I) or a salt thereof or an N-oxide: [Formula I]

[Wherein, R ¹ is a hydroxyl group, a halogen atom, a cyano group, a nitro group, a formyl group, a C _1-6 alkyl group, C _2-6 alkenyl group, C _2-6 alkynyl group, which may be substituted with G ¹ , C _1-6 haloalkyl group, C _1-6 haloalkenyl group, C _1-6 alkylcarbonyl group, C _1-6 alkoxy group which may be substituted with G ² , C _1-6 haloalkoxy group, C _2-6 alkenyl jade group, a C _2-6 haloalkenyl group, a C _2-6 alkynyl group, a C _1-6 alkylcarbonyloxy group, C _1-6 alkoxy carbonyloxy group, C _1-6 alkylthio carbonyloxy group, an amino group which may be substituted by G ^3, C _1-6 alkylthio, C _1-6 halo-alkyl group, C _1-6 alkylsulfinyl group, C _1-6 haloalkylsulfinyl group, C _1-6 alkylsulfonyl group , C _1-6 haloalkylsulfonyl group, C _1-6 alkylsulfonyloxy group, C _1-6 haloalkylsulfonyloxy group, heterocyclic group which may be substituted with G ⁴ (selected from oxygen atom, nitrogen atom and sulfur atom) 5 or 6 membered heterocyclic group having one or more heteroatoms), and It refers to any one of substituents represented by the formula:

(Wherein R ⁸ and R ⁹ each independently represent a C _1-6 alkyl group, Y ¹ , Y ² and Y ³ each independently represent an oxygen atom or a sulfur atom, and A may be substituted with G ⁴ ) Heterocyclic group (a 5 or 6 membered heterocyclic group having one or more heteroatoms selected from an oxygen atom and a nitrogen atom), R ¹⁰ represents a C _1-6 alkyl group, a C _2-6 alkenyl group, a C _2-6 alkynyl group, C _1-6 alkyl C _1-6 alkoxy group, C _1-6 haloalkyl group, or a heterocyclic group which may be substituted with G ⁴ (5 or 6 having one or more heteroatoms selected from oxygen atom, nitrogen atom and sulfur atom) Ring heterocyclic group), R ¹¹ and R ¹² each independently represent a hydrogen atom, a C _1-6 alkyl group, a C _2-6 alkenyl group or a C _2-6 alkynyl group, and R ¹³ and R ¹⁴ each independently A C _1-6 alkyl group, R ¹³ and R ¹⁴ may be bonded together to form a ring}; m represents 0 or an integer from 1 to 5, R ² is a heterocyclic group which may be substituted with a halogen atom, a nitro group, a C _1-6 alkyl group, a C _1-6 alkoxy group, a C _1-6 haloalkyl group, G ⁴ (oxygen atom, nitrogen atom and sulfur atom) 5 or 6 membered heterocyclic group having one or more heteroatoms), or a C _1-6 haloalkoxy group, k represents an integer of 0 or 1 to 4, R ³ , R ³¹ , R ⁴ , R ⁴¹ , R ⁵ , R ⁵¹ , R ⁶ , R ⁶¹ and R ⁷ are each independently a hydrogen atom, a C _1-6 alkyl group, a C _1-6 alkoxycarbonyl group or C _1-6 An alkoxy group, R ³ and R ⁴ may be taken together or R ⁵ and R ⁶ may be bonded together to form a saturated ring, X represents an oxygen atom, a sulfur atom, a sulfinyl group or a sulfonyl group, G ¹ is a hydroxyl group, a C _1-6 alkoxycarbonyl group, a C _1-6 alkoxy group, a C _1-6 alkoxy C _1-6 alkoxy group, a heterocyclic group which may be substituted with G ⁴ (oxygen atom, nitrogen atom and sulfur 5 or 6 membered heterocyclic group having one or more heteroatoms selected from atoms), or a C _3-6 cycloalkyl group, G ² is hydroxyl group, a cyano group, an amino group which may be substituted by G ^4, C _1-6 alkoxy group, C _1-6 alkylthio, C _1-6 alkylsulfonyl, C _1-6 alkoxy groups, C _{A 1-6} alkoxy C _1-6 alkoxy group, a C _3-6 cycloalkyl group, or a C _6-10 aryl group which may be substituted with a halogen atom or a C _1-6 alkyl group, G ³ represents a C _1-6 alkyl group, C _1-6 alkylcarbonyl group or C _1-6 alkylsulfonyl group, G ⁴ represents a C _1-6 alkyl group or C _1-6 alkoxy group, n represents 0 or 1].