Amide compounds and use thereof

Abstract

An amide compound given by formula [I]: 1

Description

TECHNICAL FIELD

[0001] The present invention relates to amide compounds and their use for fungicide.

BACKGROUND ARTS

[0002] The present invention provides an amide compound which can be more excellent fungicidal active ingredient, though various fungicides for controlling plant diseases have been known hitherto.

DISCLOSURE OF THE INVENTION

[0003] The present invention provides an amide compound given by formula [I]: 2

[0004] wherein R1 represents a C1-C10 haloalkyl group, C2-C10 haloalkonyl group, C3-C10 haloalkynyl group, C3-C8 halocycloalkyl group or C3-C10 alkynyl group; R2 represents a hydrogen atom or C1-C3 alkyl group (namely, methy, ethyl, propyl and isopropyl); X represents an oxygen atom or sulfur atom; Y represents an oxygen atom or sulfur atom; Ar represents an aromatic group; A represents an ethylene group or trimethylene group, said ethylene group and trimethylene group may be substituted by one or more selected from halogen atom, amino group, hydroxy group, cyano group, nitro group, C1-C6 alkyl group, C3-C6 cycloalkyl group, C3-C6 cycloalkenyl group, C1-C6 alkoxy group, C1-C6 haloalkoxy group, C1-C6 alkylthio group, C1-C6 haloalkylthio group, C2-C6 (alkoxycarbonyl) group and tri(C1-C6 alkyl)silyl group; Z1 and Z2 are the same or different and represents a halogen atom (chlorine, bromine, fluorine, iodine), C1-C6 alkyl group, C1-C6 haloalkyl group, C2-C6 alkenyl group, C2-C6 alkynyl group, C3-C6 cycloalkyl group, C1-C6 alkoxy group, C1-C6 haloalkoxy group, C2-C6 (alkoxyalkoxy) group, C4-C6 (cycloalkylalkoxy) group, C3-C6 alkenyloxy group, C3-C6 haloalkenyloxy group, C3-C6 alkynyloxy group, C3-C6 haloalkynyloxy group, C3-C6 cycloalkoxy group, C3-C6 cycloalkenyloxy group, cyano C1-C5 alkoxy group, C1-C6 alkylthio group, C1-C6 haloalkylthio group (C1-C5 alkoxy)carbonyl group, phenoxy group, benzyloxy group, hydroxy group or cyano group, the benzene ring of said phenyl group and benzyloxy group may be substituted by one or more selected from halogen atom (chlorine, bromine, fluorine, iodine) C1-C6 alkyl group, C1-C6 alkoxy group, trifluoromethyl group, amino group and nitro group; and Z1 and Z2 may represents C2-C6 alkylenedioxy group together, (heeinafter, referred to as the present compound) and fungicide comprising it as an active ingredient.

[0005] In the present invention, examples of the C1-C10 haloalkyl group for R1 include fluoromethyl, difluoromethyl, trifluoromethyl, chlorodifluoromethyl, chlorofluoromethyl, bromodifluoromethyl, trichloromethyl, dichlorobromomethyl, 1,1,2,2,2-pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2-difluoroethyl and 2-fluoroethyl; examples of the C2-C10 haloalkenyl group include 2-fluorovinyl, 2,2-difluorovinul, trifluorovinyl, 3-chloropropenyl, 3,3-dichloropropenyl, 3-fluoropropenyl, 3,3-difluoropropenyl, 2,3,3-trifluoropropenyl and 10-fluoro-2-decenyl; examples of the C3-C10 haloalkynyl group include 3-fluoro-2-propynyl, 3-chloro-2-propynyl, 3-bromo-2-propynyl, 3-iodo-2-propynyl, 4-fluoro-2-butynyl, 4,4-difluoro-2-butynyl, 4,4,4-trifluoro-2-butynyl and 4-chloro-2-butynyl; examples of the C3-C8 halocycloalkyl group include 2,2-difluorocyclopropyl, 2,3,4-trifluorocyclobutyl, 2,5-dichlorocyclopentyl, 4,4-difluorocyclohexy and 2-chlorocycloheptyl; and examples of the C3-C10 alkynyl group include 2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 5-pentynyl and 7-octynyl. Among them, C1-C3 haloalkyl group, C2-C3 haloalkenyl group, C3-C5-haloalkynyl group, C3-C6 halocycloalkyl group and C3-C8 alkynyl group are preferable, and especialy fluoromethyl, difluoromethyl, trifluoromethyl and 2-propynyl are more preferable for R1.

[0006] In the present invention, examples of the aromatic group for Ar include aromatic hydrocarbyl groups such as phenyl, naphthyl (1-naphthyl, 2-naphthyl) and so on; and aromatic heterocyclic groups such as thienyl (2-thienyl, 3-thienyl), furyl (2-furyl, 3-furyl), pyrrolyl (1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl), pyrazolyl (1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl), imidazolyl (1-imidazolyl, 2-imidazolyl, 4-imidazolyl), triazolyl (1-triazolyl, 4-triazolyl), tetrazolyl (1-tetrazolyl, 5-tetrazolyl), thiazolyl (2-thiazolyl, 4-thiazolyl, 5-thiazolyl), isothiazolyl (3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl), oxazolyl (2-oxazolyl, 4-oxazolyl, 5-oxazolyl), isoxazolyl (3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl), thiadiazolyl (e.g. 1,2,5-thiadiazol-4-yl, 1,3,4-thiadiazol-2-yl, 1,2,3-thiadiazol-5-yl), pyridyl (2-pyridyl, 3-pyridyl, 4-pyridyl), pyrimidinyl (2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl), pyrazinyl, pyridazinyl (3-pyridazinyl, 4-pyridazinyl), benzofuryl (2-benzofuryl, 3-benzofuryl, 4-benzofuryl, 5-benzofuryl, 6-benzofuryl, 7-benzofuryl), benzothienyl (2-benzothienyl, 3-benzothienyl, 4-benzothienyl, 5-benzothienyl, 6-benzothienyl, 7-benzothienyl), indolyl (1-indolyl, 2-indolyl, 3-indolyl, 4-indolyl, 5-indolyl, 6-indolyl, 7-indolyl), benzothiazolyl (2-benzothiazolyl, 4-benzothiazolyl, 5-benzothiazolyl, 6-benzothiazolyl, 7-benzothiazolyl), benzimidazolyl (1-benzimidazolyl, 2-benzimidazolyl, 4-benzimidazolyl, 5-benzimidazolyl, 6-benzimidazolyl, 7-benzimidazolyl), benzopyrazolyl (1-benzopyrazolyl, 2-benzopyrazolyl, 3-benzopyrazolyl, 4-benzopyrazolyl, 5-benzopyrazolyl, 6-benzopyrazolyl, 7-benzopyrazolyl), quinolyl (2-quinolyl, 3-quinolyl, 4-quinolyl, 5-quinolyl, 6-quinolyl, 7-quinolyl, 8-quinolyl), isoquinolyl (1-isoquinolyl, 3-isoquinolyl, 4-isoquinolyl, 5-isoquinolyl, 6-isoquinolyl, 7-isoquinolyl, 8-isoquinolyl), pyrazolopyrimidinyl, imidazopyrimidinyl, thiophenopyrimidinyl, thiazolopyrimidinyl, pyrazolopyridyl, imidazopyridyl, thiophenopyridyl, thiazolopyridyl and so on; and said aromatic hydrocarbyl group and aromatic heterocyclic group may be substituted. Typical examples of the substituents include halogen (chlorine, bromine, fluorine, iodine), amino, hydroxy, cyano, nitro, C1-C10 alkyl (e.g. methyl, ethyl, propyl, isopropyl, butyl, isobutyl, 1-methylpropyl, pentyl, 1-methylbutyl, 1-ethylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1,2-dimethylbutyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl, 1-ethylpentyl, 3,3-dimethylbutyl, heptyl, 3,7-dimethyloctyl), C1-C10 haloalkyl (e.g. trifluoromethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl), cyano C1-C9 alkyl (e.g. cyanomethyl, 1-cyanoethyl, 2-cyanoethyl, 3-cyanopropyl, 5-cyanohexyl), C2-C10 alkenyl (e.g. vinyl, 1-propenyl, 2-propenyl, 1-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 3,3-dimethyl-1-butenyl, 4-pentenyl, 5-hexenyl), C2-C10 haloalkenyl (e.g. 2-fluorovinyl, 3-chloro-2-propenyl, 3,3-dichloro-2-propenyl, 2-fluoro-1-propenyl, 3,3,3-trifluoro-1-propenyl, 4-chloro-3-butenyl, 2-chloro-3-methyl-1-butenyl, 2-fluoro-5-hexenyl), C2-C10 alkynyl (e.g. ethynyl, 1-propynyl, 2-propynyl, 1-methyl-2-propynyl, 1-ethyl-2-propynyl, 1-butynyl, 3,3-dimethyl-1-butynyl, 3-butynyl, 4-pentynyl, 5-hexynyl), C2-C10 haloalkynyl (e.g. 2-fluoroethynyl, 2-chloroethynyl, 3-chloro-2-propynyl, 4-fluoro-3-butynyl, 5-chloro-4-pentynyl, 6-bromo-5-hexynyl), C3-C6 cycloalkyl (e.g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl), C3-C6 cycloalkenyl (e.g. 2-cyclopentenyl, 2-cyclohexenyl), C1-C10 alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, pentyloxy), C1-C10 haloalkoxy (e.g. trifluoromethoxy, difluoromethoxy, bromodifluoromethoxy, chlorodifluoromethoxy, fluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy), C3-C10 alkenyloxy (e.g. 2-propenyloxy, 1-methyl-2-propenyloxy, 1-ethyl-2-propenyloxy, 2-butenyloxy, 3-butenyloxy, 2,2-dimethyl-3-butenyloxy, 4-pentenyloxy, 5-hexenyloxy), C3-C10 haloalkenyloxy (e.g. 3-chloro-2-propenyloxy, 3,3-dichloro-2 -propenyloxy, 2-fluoro-1-propenyloxy, 3,3,3-trifluoro-1-propenyloxy, 4-chloro-3-butenyloxy, 2-chloro-3-methyl-1-butenyloxy, 2-fluoro-5-hexenyloxy), C3-C10 alkynyloxy (e.g. 2-propynyloxy, 1-methyl-2-propynyloxy, 1-ethyl-2-propynyloxy, 2-butynyloxy, 3-butynyloxy, 4-pentynyloxy, 5-hexynyloxy), C3-C10 haloalkynyloxy (e.g. 3-chloro-2-propynyloxy, 3-fluoro-2-propynyloxy, 4-fluoro-3-butynyloxy, 5-chloro-4-pentynyloxy, 6-bromo-5-hexynyloxy), C3-C10 cycloalkoxy (e.g. cyclopropoxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy, cyclooctyloxy), cyano C1-C9 alkoxy (e.g. cyanomethoxy, 1-cyanoethoxy, 2-cyanoethoxy, 3-cyanopropoxy, 5-cyanohexyloxy), C1-C10 alkylthio (e.g. methylthio, ethylthio, propylthio, butylthio, isobutylthio, sec-butylthio, pentylthio, hexylthio), C1-C10 haloalkylthio (e.g. trifluoromethylthio, difluoromethylthio, bromodifluoromethylthio, chlorodifluoromethylthio, fluoromethylthio, 2,2,2-trifluoroethylthio, 1,1,2,2-tetrafluoroethylthio), C2-C10 (alkoxycarbonyl) (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl), tri(C1-C6 alkyl)silyl (e.g. trimethylsilyl, triethylsilyl), C3-C5 alkylene (e.g. trimethylene, tetramethylene, pentamethylene) and methylenedioxy. Among them, preferred Ar's are 4-methylphenyl group, 4-ethylphenyl group, 4-methoxyphenyl group, 4-chlorophenyl group, 4-trifluoromethylphenyl group, 3,4-tetramethylenephenyl group (5,6,7,8-tetrahydronaphthalen-2-yl group), 3,4-trimethylenephenyl group (indan-5-yl group) and 2-naphthyl group.

[0007] In the present invention, the ethylene group (—CH2CH2—) and trimethylene group for A may be substituted by at least one selected from halogen (chlorine, bromine, fluorine, iodine), amino, hydroxy, cyano, nitro, C1-C6 alkyl (e.g. methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, t-butyl), C3-C6 cycloalkyl (e.g. cyclopropyl, cyclopentyl, cyclohexyl), C3-C6 cycloalkenyl, C1-C6 alkoxy (e.g. methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy, pentyloxy), C1-C6 haloalkoxy (e.g. trifluoromethoxy, difluoromethoxy, bromodifluoromethoxy, chlorodifluoromethoxy, fluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy), C1-C6 alkylthio (e.g. methylthio, ethylthio, propylthio, butylthio, isobutylthio, sec-butylthio, pentylthio, hexylthio), C1-C6 haloalkylthio (e.g. trifluoromethylthio, difluoromethylthio, bromodifluoromethylthio, chlorodifluoromethylthio, fluoromethylthio, 2,2,2-trifluoroethylthio, 1,1,2,2-tetrafluoroethylthio), C2-C6 (alkoxycarbonyl) (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl) and (C1-C6 alkyl)silyl (e.g. trimethylsilyl, triethylsilyl). Among them, ethylene (—CH2CH2—) is preferable for A.

[0008] In the present invention, examples of the C1-C6 alkyl group for Z1 and Z2 include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, 1-methylbutyl, 1-ethylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, hexyl, 1-methylpentyl and 3,3-dimethylbutyl; examples of the C1-C6 haloalkyl group include trifluoromethyl, 2,2,2-trifluoroethyl and 1,1,2,2-tetrafluoroethyl; examples of the C2-C6 alkenyl group include vinyl, 2-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 4-methyl-3- butenyl, 4-pentenyl and 5-hexenyl; C2-C6 alkynyl group include ethynyl, 2-propynyl, 1-methyl-2-propynyl, 1-ethyl-2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-butynyl, 2-pentynyl and 4,4-dimethyl-2-pentynyl; examples of the C3-C6 cycloalkyl group include cyclopropyl, cyclopentyl and cyclohexyl; examples of the C1-C6 alkoxy group include methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy and pentyloxy; examples of the C1-C6 haloalkoxy group include trifluoromethoxy, difluoromethoxy, bromodifluoromethoxy, chlorodifluoromethoxy, fluoromethoxy, 2,2,2-trifluoroethoxy and 1,1,2,2-tetrafluoroethoxy; examples of the C2-C6 (alkoxyalkoxy) group include methoxymethoxy, 2-methoxyethoxy, ethoxymethoxy and isopropoxymethoxy; examples of the C4-C6 (cycloalkylalkoxy) group include cyclopropylmethyl; examples of the C3-C6 alkenyloxy group include 2-propenyloxy, 1-methyl-2-propenyloxy, 2-methyl-2-propenyloxy, 2-butenyloxy, 3-butenyloxy, 3-methyl-2-butenyloxy, 4-methyl-3- butenyloxy, 4-pentenyloxy and 5-hexenyloxy; examples of the C3-C6 haloalkenyloxy group include 2-chloro-2-propenyloxy, 3-fluoro-2- propenyloxy, 3-chloro-2-propenyloxy, 3-bromo-2-propenyloxy, 3,3-dichloro-2-propenyloxy, 2,3, 3-trifluoro-2-propenyloxy, 4-chloro-2-butenyloxy, 4-chloro-3-butenyloxy and 3-chloro-3-butenyloxy; examples of the C3-C6 alkynyloxy group include 2-propynyloxy, 1-methyl-2-propynyloxy, 1-ethyl-2-propynyloxy, 2-butynyloxy, 3-butynyloxy, 1-methyl-2-butynyloxy, 2-pentynyloxy, 4-pentynyloxy and 4,4-dimethyl-2-pentynyloxy; examples of the C3-C6 haloalkynyloxy group include 3-fluoro-2-propynyloxy, 3-chloro-2-propynyloxy, 3-bromo-2-propynyloxy, 3-chloro-1-methyl-2-propynyloxy, 4,4,4-trifluoro-2-butynyloxy, 4-chloro-3-butynyloxy and 5-chloro-4-pentynyloxy; examples of the C3-C6 cycloalkoxy group include cyclopropoxy, cyclopentyloxy and cyclohexyloxy; examples of the C3-C6 cycloalkenyloxy group include cyclopentenyloxy and cyclohexenyloxy; examples of the cyano C1-C5 alkoxy group include cyanomethoxy, 1-cyanoethoxy and 2-cyanoethoxy; examples of the C1-C6 alkylthio group include methylthio, ethylthio, propylthio, butylthio, isobutylthio, sec-butylthio, pentylthio and hexylthio; examples of the C1-C6 haloalkylthio group include trifluoromethylthio, difluoromethylthio, bromodifluoromethylthio, chlorodifluoromethylthio, fluoromethylthio, 2,2,2-trifluoroethylthio and 1,1,2,2-tetrafluoroethylthio; examples of the (C1-C5 alkoxy)carbonyl group include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl and pentyloxycarbonyl; examples of the optionally substituted phenoxy group include phenoxy, 4-chlorophenoxy, 4-methylphenoxy, 4-methoxyphenoxy and 4-trifluoromethylphenoxy; examples of the optionally substituted benzyloxy group include benzyloxy, 4-chlorobenzyloxy, 4-methylbenzyloxy, 4-methoxybenzyloxy and 4-trifluoromethylbenzyloxy; and examples of the C2-C6 alkylenedioxy group include ethylenedioxy, propylenedioxy and trimethylenedioxy. Among them, preferable are methoxy for Z1 and methoxy and 2-propynyloxy for Z2.

[0009] In the present compounds, there exist (E) and (Z) isomers based on C═C double bond bonded with Ar and X, and the present invention include each isomer and mixtures thereof.

[0010] In the present compounds, the compounds having excellent efficacy for controlling plant diseases are exemplified by N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2 -(4-methylphenyl)acrylamide, N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-[2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(5,6,7,8 -tetrahydronaphthalen-2-yl)acrylamide, N-[2-{3-methoxy-4-(2-propynyloxy) phenyl}ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide, N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide and N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(4-chlorophenyl) acrylamide.

[0011] The present compounds can be produced, for example, by the following [Production method A], [Production method B] or [Production method C]. In these production methods, a protective group may be utilized for protecting a functional group from chemical reaction, if necessary.

[0012] [Production Method A]

[0013] Production method of making the compound given by formula [II] to react with the compound given by formula [III] 3

[0014] In the above scheme, L1 represents a leaving group such as chlorine, bromine, iodine, p-toluenesulfonyloxy, methanesulfonyloxy and trifluoromethanesulfonyl; R11 represents C1-C10 haloalkyl group such as fluoromethyl, difluoromethyl, bromodifluoromethyl and fluoroethoxy, C3-C10 haloalkenyl group such as 3,3-dichloroally or C3-C10 haloalkynyl group such as 2-propynyl; and R2, X, Y, Ar, A, Z1 and Z2 have the same meanings as defined above.

[0015] Step 1 (process 1) in the above scheme is a process for producing the present compound given by formula [I-1] by making the compound given by formula [II] react with the compound given by formula [III] optionally in the presence of a base. The reaction temperature is usually in the range of 0-100° C. and the reaction period is usually in the range of 1-24 hours. The amount of the compound given by formula [III] utilized for the reaction is usually 0.5-10 mols, preferably 1-3 mols based on 1 mol of the compound given by formula [II].

[0016] When the base is utilized for the reaction, the amount of the base is usually 1-10 mols moles based on 1 mol of the compound given by formula [II]. Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydride and the like; organic bases such as pyridine, triethylamine, ethyldiisopropylamine and the like; and mixtures thereof.

[0017] The reaction is usually carried out in a solvent. Examples of the solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; organic bases such as pyridine, triethylamine and N,N-dimethylaniline; esters such as butyl acetate and ethyl acetate; nitrites such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; water; and mixtures thereof.

[0018] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0019] The compound given by formula [I] wherein R1 is trifluoromethyl can be prepared according to the methods described in Tetrahydron Lett., 1973, 2253 and J. Org. Chem., 1979, 44, 3872. At that time, Production Example 15 given below can be comferred.

[0020] The compound given by formula [II] wherein X is oxygen and Y is also oxygen (the compound given by formula [II-1] in the scheme below) can be prepared according to the methods described in Chem. Ber., 1971, 104, 2709, J. Org. Chem., 1966, 61, 3358 and Adv. Heterocycl. Chem., 1981, 31, 207. It can be concretely produced according to the following scheme. 4

[0021] In the above scheme, L3 and L4 are the same or different and represent alkoxy group such as t-butoxy group; L2 represents chlorine or bromine atom; and R2, Ar A, Z1 and Z2 have the same meanings as defined above.

[0022] The step 2-1 is a step of making the compound given by formula [IV] react with the compound given by formula [V] in the presence of a base to provide the compound given by formula [VI]. The reaction temperature is usually in the range of 0 to 100° C. and the amount of the compound given by formula [V] is usually 1 to 5 mols based on 1 mol of the compound given by formula [IV].

[0023] The amount of the base used for the reaction is usually 1 to 10 mols based on 1 mol of the compound given by formula [IV]. Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and sodium hydride; organic bases such as pyridine, triethylamine and ethyldiisopropylamine; and mixtures thereof.

[0024] The reaction is usually carried out in a solvent and examples of the solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; organic bases such as pyridine, triethylamine and N,N-dimethylaniline; esters such as butyl acetate and ethyl acetate; nitrites such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; water; and mixtures thereof.

[0025] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0026] The step 2-2 is a step of making the compound given by formula [VI] react with the compound given by formula [VII-1] or formula [VII-2] to provide the compound given by formula [VIII]. The reaction temperature is usually in the range of 50 to 150° C., the reaction period is usually in the range of 1 to 24 hours and the amount of the compound given by formula [VII-1] or formula [VII-2] is usually 1 to 10 mols based on 1 mol of the compound given by formula [VI].

[0027] The reaction is usually carried out in a solvent and examples of the solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; organic bases such as pyridine, triethylamine and N,N-dimethylaniline; nitrites such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; and mixtures thereof.

[0028] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0029] The step 2-3 is a step of making the compound given by formula [VIII] react with excess water in the presence of an acid to provide the compound given by formula [II-1]. The reaction temperature is usually in the range of 0 to 100° C. and examples of the acid include hydrochloric acid, sulfuric acid and p-toluenesulfonic acid. The amount of the acid is usually 0.1 to 100 mols based on 1 mol of the compound given by formula [VIII].

[0030] The reaction can be carried out in a solvent and examples of the solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; nitriles such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; and mixtures thereof.

[0031] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0032] [Production method B]

[0033] Production method of making the compound given by formula [I-1] to react with 2,4-bis(4-methoxyphenyl)-1,3-dithia-2,4-diphosphetane-2,4-disulfide (hereinafter, referred to as Lawesson's Reagent) 5

[0034] In the above scheme, R1, R2, X, Ar, A, Z1 and Z2 have the same meanings as defined above.

[0035] The step 3 is a step of making the compound given by formula [I-1] react with Lawesson's Reagent in a solvent to provide the compound given by formula [I-2]. The reaction temperature is usually in the range of 50 to 150° C. and the amount of the Lawesson's Reagent is usually 1 to 10 mols based on 1 mol of the compound given by formula [I-1].

[0036] Examples of the solvent used for the reaction include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; organic bases such as pyridine, triethylamine and N,N-dimethylaniline; nitriles such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; and mixtures thereof.

[0037] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0038] [Production method C]

[0039] Production method of making the compound given by formula [IX] to react with the compound given by formula [X] 6

[0040] In the above scheme, L5 represents p-toluenesulfonyl, methanesulfonyl or trifluoromethanesulfonyl, and R1, R2, Y, Ar, A, Z1 and Z2 have the same meanings as defined above.

[0041] The step 4 is a step of making the compound given by formula [IX] react with the compound given by formula [X]optionally in the presence of a base to provide the present compound given by formula [I]. The reaction temperature is usually in the range of 0 to 100° C., the reaction period is usually in the range of 1 to 24 hours and the amount of the compound given by formula [X] is usually 0.5 to 10 mols, preferably 1 to 3 mols based on 1 mol of the compound given by formula [IX].

[0042] When the base is utilized in the above reaction, the amount of the base is usually 1 to 10 mols based on 1 mol of the compound given by formula [X]. Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and sodium hydride; organic bases such as pyridine, triethylamine and ethyldiisopropylamine; and mixtures thereof.

[0043] The reaction is usually carried out in a solent and examples of the solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; organic bases such as pyridine, triethylamine and N,N-dimethylaniline; esters such as butyl acetate and ethyl acetate; nitriles such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; water; and mixtures thereof.

[0044] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0045] The compound given by formula [IX] can be, for example, produced according to the following scheme. 7

[0046] In the above scheme, L5, R2, Ar, A, Z1 and Z2 have the same meanings as defined above.

[0047] The step 5 is a step of making the compound given by formula [II-1] react with the compound given by formula [X]optionally in the presence of a base to provide the present compound given by formula [IX]. The reaction temperature is usually in the range of −20 to 100° C., the reaction period is usually in the range of 1 to 24 hours and the amount of the compound given by formula [XI] is usually 0.5 to 10 mols, preferably 1 to 3 mols based on 1 mol of the compound given by formula [IX].

[0048] When the base is utilized in the above reaction, the amount of the base is usually 1 to 10 mols based on 1 mol of the compound given by formula [II-1]. Examples of the base include inorganic bases such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and sodium hydride; organic bases such as pyridine, triethylamine and ethyldiisopropylamine; and mixtures thereof.

[0049] The reaction is usually carried out in a solent and examples of the solvent include ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether and t-butyl methyl ether; aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as toluene; halogenated hydrocarbons such as chlorobenzene; organic bases such as pyridine, triethylamine and N,N-dimethylaniline; esters such as butyl acetate and ethyl acetate; nitriles such as acetonitrile; N,N-dimethylformamide; dimethyl sulfoxide; water; and mixtures thereof.

[0050] The reaction solution after the reaction is subjected to usual work-up such as extraction with organic solvent, concentration and so on to provide the isolated objective product. The objective product can be purified by recrystallization, distillation, chromatography and so on.

[0051] The compound given by formula [IV] can be, for example, produced according to the following scheme. 8

[0052] wherein L2 and Ar mean as described above.

[0053] The compound given by formula [XII] can be produced according to the description in Syn. Commun., 1982, 21, 415, JP sho58-41862A, Tetrahedron Lett., 1980,21,2547, Syn. Commun., 1976, 6, 349 and J. Am. Chem. Soc., 1977, 99, 4833.

[0054] The compound given by formula [V] can be produced according to the description in Bull. Chem. Soc, Jpn., 1990, 63, 1252, J. Am. Chem. Soc., 1955, 77, 2544, Synthesis, 1975, 590 and Chem. Lett., 1984, 1733.

[0055] When the present compound is used as an active ingredient of fungicide, it can be used as it is without any other ingredient, but it is usually formulated to emulsifiable concentrates, wettable powders, water dispersible granules, emulsion formulations, flowables, dusts, granules and so on by mixing with solid carrier, liquid carrier, surfactant or the other auxiliaries and used. These formulations usually contain 0.1 to 90% by weight of the present compound.

[0056] Examples of the solid carrier utilized for the formulation include fine powders or granules of minerals such as kaolin clay, attapulgite clay, bentonite, montmorillonite, terra alba, pyrophilite, talc, diatomaceous earth and calcite; natural organic substances such as corncob and walnut shell; synthetic organic substances such as urea; salts such as calcium carbonate and ammonium sulfate; and synthetic inorganic substances such as synthetic hydrous silicon oxide. Examples of the liquid carrier include aromatic hydrocarbons such as xylene, alkylbenzene and methylnaphthalene; alcohols such as isopropanol, ethylene glycol, propylene glycol and cellosolve; ketones such as acetone, cyclohexanone and isophorone; vegetable oils such as soybean oil and cottonseed oil; paraffin type aliphatic hydrocarbons; esters; dimethyl sulfoxide; acetonitrile and water.

[0057] Examples of the surfactant include anionic surfactants such as alkylsulfate ester salts, alkylarylsulfonate salts, dialkyl sulfosaccinate salts, polyoxyethylenealkylary ether phosphate salts, ligninsulfonate salts and naphthalenesulfonate formaldehyde condensate; nonionic surfactants such as polyoxyethylenealkylary ether, polyoxyethylenealkylpolyoxypropylene block copolymers and sorbitan fatty acid esters.

[0058] Examples of the auxiliaries for formulation include water soluble polymers such as polyvinyl alcohol and polyvinylpyrrolidone; polysaccharides such as gum arabic, algin acid and its salts, CMC(carboxymethylcellulose) and xanthan gum; inorganic substances such as alminium magnesium silicate and almina sol; preservatives; coloring agent; PAP (isopropyl acid phosphate) and stabilizers such as BHT.

[0059] The application methods of the present compounds are typically foliar application and soil treatment.

[0060] When the present compound is used for controlling plant diseases, the dosage is usually 1 to 5000 g, preferably 5 to 1000 g per 1 hectare though it is variable depending on the type of plants (e.g. crops) to be treated, type of diseases to be controlled, degree of affection by the diseases, formulation type, application method, time of application, weather conditions and so on.

[0061] In case emulsifiable concentrates, wettable powders, flowables and the like are used as aqueous dilution, the concentration of the active ingredient is 0.0001 to 3% by weight, preferably 0.0005 to 1% by weight. Dusts, granules and the like are applied as they are without dilution. The present compound is also used for the other known application methods such as seed treatment. When it is used for seed treatment, seeds are usually soaked in 1 to 1000 ppm dilution of the present compound, or said dilution is sprayed to or daubed on the seeds. Further, dusts containing 0.1 to 10% by weight of the present compound may be applied by powder treatment.

[0062] The present compound can be used as agricultural/horticultural fungicide for controlling plant diseases in the plowed fields, paddy fields, orchards, tea plantations, pastures, lawns and the like. Also, an increased fungicidal effect can be expected by using the compounds in admixture with other fungicides. Examples of such admixable other fungicide include azole type fungicidal compounds such as propiconazole, triadimenol, prochloraz, penconazole, tebuconazole, flusilazole, diniconazole, bromconazole, epoxyconazole, diphenoconazole, ciproconazole, metoconazole, triflumizole, tetraconazole, microbutanil, fenbuconazole, hexaconazole, fluquinconazole, triticonazole, bitertanol, imazalil and flutriafol; cyclic amine type fungicidal compounds such as fenpropimorph, tridemorph and fenpropidin; benzimidazole type fungicidal compounds such as carbendazim, benomyl, thiabendazole and thiophanate-methyl; procymidone; cyprodinil; pyrimethanil; diethofencarb; thiuram; fluazinam; mancozeb; iprodione; vinclozolin; chlorothalonil; captan; mepanipyrim; fenpiclonil; fludioxonil; dichlofluanide; folpet; kresoxim-methyl; azoxystrobin; trifloxystrobin; picoxystrobin; pyraclostrobin; N-methyl- α-ethoxyimino-2-[(2,5-dimethylphenoxy) methyl]phenylactamide, spiroxamine; quinoxyfen; phenhexamid; famoxadone; fenamidon (RP-407213) and iprovalicarb.

[0063] The present compound can be used in combination with other agricultural/horticultural insecticides, acaricides, nematocides, herbicides, plant growth regulators and fertilizers. In the combination, they can be mixed in advance.

[0064] Examples of the insecticide, acaricide and nematocide include organophosphorus compounds such as fenitrothion [O,O-dimethyl O-(3-methyl-4 -nitrophenyl) phosphorothioate], fenthion [O,O-dimethyl O-(3-methyl-4-(methythio) phenyl) phosphorothioate], diazinon [O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4 -yl phosphorothioate], chlorpyrifos [O,O-diethyl O-3,5,6-trichloro-2 -pyridyl phosphorothioate], acephate [O,S-dimethyl acetylphosphoramidothioate], methidathion [S-2,3-dihydro-5-methoxy- 2-oxo-1,3,4-thiadiazol-3-ylmethyl O,O-dimethyl phosphorodithioate], disulfoton [O,O-diethyl S-2-ethylthioethyl phosphorodithioate], DDVP [2,2-dichlorovinyl dimethyl phosphate], sulprofos [O-ethyl O-4-(methylthio)phenyl S-propyl phosphorodithioate], cyanophos [O-4-cyanophenyl O,O-dimethyl phosphorothioate], dioxabenzofos [2-methoxy-4H-1,3,2-benzodioxaphosphorin 2-sulfide], dimethoate [O,O-dimethyl S-(N-methylcarbamoylmethyl) dithiophosphate], phenthoate [ethyl 2-dimethoxyphosphinothioylthio(phenyl) acetate], malathion [diethyl (dimethoxyphosphinothioylthio) succinate], trichlorfon [dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate], azinphosmethyl [S-3,4-dihydro-4-oxo-1,2,3-benzotriazin-3-ylmethyl O,O-dimethyl phosphorodithioate], monocrotophos [dimethyl (E)-1-methyl-2-(methylcarbamoyl) vinyl phosphate], ethion [O,O,O′,O′-tetraethyl S,S′-methylene bis (phosphorodithioate)] and fosthiazate [N-(O-methyl-S-sec-butyl) phosphorylthiazolidin-2-one]; carbamate compounds such as BPMC [2-sec-butylphenyl methylcarbamate], benfracarb [ethyl N-[2,3-dihydro-2,2-dimethylbenzofuran-7 -yloxycarbonyl(methyl)aminothio]-N-isopropyl-β-alaninate], propoxur [2- isopropoxyphenyl N-methylcarbamate], carbosulfan [2,3-dihydro-2,2-dimethyl-7 -benzo [b]furanyl N-dibuthylaminothio-N-methylcarbamate], carbaryl [1-naphthyl N-methylcarbamate], methomyl [S-methyl N-[(methylcarbamoyl)oxy]thioacetimidate], ethiofencarb [2-(ethylthiomethyl) phenyl methylcarbamate], aldicarb [2-methyl-2-(methylthio)propionaldehyde O-methylcarbamoyloxime], oxamyl [N,N-dimethyl-2-methylcarbamoyloxyimino-2 -(methylthio)acetamide] and fenothiocarb [S-4-phenoxybuthyl N,N-dimethylthiocarbamate]; pyrethroid compounds such as etofenprox [2-(4-ethoxyphenyl)-2 -methylpropyl 3-phenoxybenzyl ether], fenvalerate [(RS)-α-cyano-3 -phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate], esfenvalerate [(S)-α-cyano-3-phenoxybenzyl (S) -2-(4-chlorophenyl)-3-methylbutyrate], fenpropathrin [(RS)-α-cyano-3-phenoxybenzyl 2,2,3,3-tetramethylcyclopropanecarboxylate], cypermethrin [(RS)-α-cyano-3-phenoxybenzyl (1RS, 3RS) -3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropanecarboxylate], permethrin [3-phenoxybenzyl (1RS,3RS)-3-(2,2-dichlorovinyl)-2, 2-dimethylcyclopropanecarboxylate], cyhalothrin [(RS)-α-cyano-3 -phenoxybenzyl (Z)-(1RS,3RS)-3-(2-chloro-3,3,3-trifluoropropenyl)-2,2-dimethylcyclopropanecarboxylate), deltamethrin [(S)-α-cyano-m-phenoxybenzyl (1R, 3R) -3-(2,2-dibromovinyl)-2,2-dimethyl-cyclopropanecarboxylate], cycloprothrin [(RS)-α-cyano-3-phenoxybenzyl (RS)-2,2-dichloro-1-(4-ethoxyphenyl) cyclopropanecarboxylate], fluvalinate [α-cyano-3-phenoxybenzyl N-(2-chloro-α,α,α-trifluoro-p-tolyl)-D-valinate], bifenthrin [2-methylbiphenyl-3 -ylmethyl (Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethyl-cyclopropanecarboxylate], acrinathrin [cyano(3-phenoxyphenyl)methyl (1R-{1α(S*), 3α(Z)})-2,2-dimethyl-3-[3-oxo-3-(2,2,2-trifluoro-1-(trifluoromethyl)ethoxy-1-propenyl) cycloprop anecarboxylate], 2-methyl-2-(4-bromodifluoromethoxyphenyl) propyl 3-phenoxybenzyl ether, tralomethrin [(S)-α-cyano-3-phenoxybenzyl (1R-cis) 3-(1,2,2,2-tetrabromoethyl)-2,2-dimethylcyclopropanecarboxylate], silafluofen [(4-ethoxyphenyl)(3-(4-fluoro-3-phenoxyphenyl)propyl) dimethylsilane]; thiadiazine derivatives such as buprofezin (2-t-butylimino-3-isopropyl-5-phenyl-1, 3,5-thiadiazin-4-one); nitroimidazolidine derivatives; nereistoxin derivatives such as cartap (S,S′-(2-dimethylaminotrimethylene)bis(thiocarbamate), thiocyclam [N,N′-dimethyl-1,2,3-trithian-5-ylamine] and bensultap [S,S′-2-dimethylaminotrimethylene di(benzenethiosulfonate)]; N-cyanoamidine derivatives such as N-cyano-N′-methyl-N′-(6-chloro-3-pyridylmethyl)acetamidine; chlorinated hydrocarbons such as endosulfan [6,7,8,9,10,10-hexachloro-1, 5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepine oxide], γ-BHC [1,2,3,4,5,6-hexachlorocyclohexane] and 1,1-bis(chlorophenyl)-2,2,2-trichloroethanol; benzoylphenylurea compounds such as chlorfluazuron [1-(3,5-dichloro-4-(3-chloro-5-trifluoromethylpyridyn-2-yloxy)phenyl)-3 -(2,6-difluorobenzoyl)urea], teflubenzuron [1-(3,5-dichloro-2,4-difluorophenyl)-3 -(2,6-difluorobenzoyl)urea] and flufenoxuron [1-(4-(2-chloro-4 -trifluoromethylphenoxy)-2-fluorophenyl)-3-(2,6-difluorobenzoyl)urea]; formamidine derivatives such as amitraz [N,N′-[(methylimino)dimethylidine]di-2,4-xylidine] and chlordimeform [N′-(4-chloro-2-methylphenyl)-N,N-dimethylmethanimidamide]; thiourea derivatives such as diafenthiuron [N-(2,6-diisopropyl-4- phenoxyphenyl)-N′-t-butylcarbodiimide]; phenylpyrazole compounds; tebufenozide [N-t-butyl-N′-(4-ethylbenzoyl)-3,5-dimethylbenzhydrazide]; 4-bromo-2-(4-chlorophenyl)-1-ethoxymethyl-5-trifluoromethylpyrrole-3-carbonitrile; bromopropylate [isopropyl 4,4′-dibromobenzilate]; tetradifon [4-chlorophenyl 2,4,5-trichlorophenyl sulfone]; quinomethionate [S,S-6-methylquinoxalin-2,3-diyl dithiocarbonate]; propargite [2-(4-t-butylphenoxy)cyclohexyl prop-2-yl sulfite]; fenbutatin oxide [bis[tris (2-methyl-2-phenylpropyl)tin]oxide]; hexythiazox [(4RS, 5RS)-5-(4-chlorophenyl)-N-chlorohexyl-4-methyl-2-oxo-1,3-thiazolidin-3-carboxamide]; clofentezine [3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine]; pyridathioben [2-t-butyl-5-(4-t-butylbenzylthio)-4-chloropyridazin-3(2H)-one]; fenpyroximate [t-butyl (E)-4-[(1,3-dimethyl-5-phenoxypyrazol-4-yl)methyleneaminooxymethyl]benzoate]; tebufenpyrad [N-(4-t-butylbenzyl)-4-chloro-3-ethyl-1-methyl-5-pyrazolecarboxamide]; polynactins complex [tetranactin, dinactin and trinactin]; milbemectin; abamectin; ivermectin; azadirachtin [AZAD]; pyrimidifen [5-chloro-N-[2-{4-(2-ethoxyethyl)-2,3-dimethylphenoxy}ethyl]-6-ethylpyrimidin-4-amine] and pymetrozine [2,3,4,5-tetrahydro-3-oxo-4-[(pyridin-3-yl)methyleneamino]-6-methyl-1,2,4-triazine.

[0065] Examples of the plant diseases to be controlled by the present compound include Pyricularia oryzae and Cochlioholus miyaheanus and Rhizoctonia solani of rice; Erysiphe graminis, Gibberella zeae, Puccinia striiformis, P. graminis, P. recondita, P. hordei, Typhula sp., Micronectriella nivalis, Ustilago tritici, U. nuda, Tilletia caries, Pseudocercosporella herpotrichoides, Rhynchosporium secalis, Septoria tritici and Leptosphaeria nodorum, of wheat and barley; Diaporthe citri, Elsinoe fawcetti, Penicillium digitatum and P. italicum of citrus; Sclerotinia mali, Valsa mali, Podosphaera leucotricha, Alternaria mali and Venturia inaequalis of apple; Venturia nashicola, V. pirina, Alternaria kikuchiana and Gymnosporangium haraeanum of pear; Sclerotinia cinerea, Cladosporium carpophilum and Phomopsis sp. of peach; Elsinoe ampelina, Glomerella cingulata, Uncinula necator, Phakopsora ampelopsidis, Guignardia bidwellii and Plasmopara viticola, of grape; Gloeosporium kaki, Cercospora kaki and Mycosphaerella nawae of Japanese persimmon; Colletotrichum lagenarium, Sphaerothecafuliginea, Mycosphaerella melonis, Fusarium oxysporum, Pseudoperonospora cubensis and Phytophthora sp. of gourd; Alternaria solani, Cladosporium fulvum, Phytophthora infestans and Pythium sp. of tomato; Phomopsis vexans and Erysiphe cichoracearum, of eggplant; Alternaria japonica and Cercosporella brassicae of Cruciferae vegetables; Puccinia allii of leek; Cercospora kikuchii, Elsinoe glycines and Diaporthe phaseolorum var. sojae of soybean; Colletotrichum lindemthianum of kidney bean; Cercospora personata and Cercospora arachidicola of peanut; Erysiphe pisi of pea; Alternaria solani and Phytophthora infestans of potato; Sphaerotheca humuli of strawberry; Exobasidium reticulatum and Elsinoe leucospila of tea; Alternaria longipes, Erysiphe cichoracearum, Colletotrichum tabacum, Peronospora tabacina and Phytophthora nicotianae of tobacco; Cercospora beticola of sugar beet; Diplocarpon rosae and Sphaerotheca pannosa of rose; Septoria chrysanthemi-indici and Puccinia horiana of chrysanthemum; and Botrytis cinerea and Sclerotinia sclerotiorum of various crops.

EXAMPLES

[0066] The present invention is explained by production examples, formulation examples and test examples below and it is not restricted by the following examples.

[0067] At first, the production examples of the present compounds and reference production examples of the intermediates of the present compounds. The numbers of the present compounds are the compound numbers described in the table below.

Production Example 1

[0068] Two hundred milligrams (200 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide (0.586 mmol), 28 mg (0.70 mmol) of 60% sodium hydride, 2 ml of anhydrous N,N-dimethylformamide and 1 ml of anhydrous diethyl ether were mixed and 0.5 ml of bromofluoromethane was added thereto at −5° C. The mixture was stirred at −5° C. for 30 minutes and then stirred at 0° C. for 1 hour. The reaction mixture was added to water and extracted with ethyl acetate. The organic layer was washed with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel preparative thin layer chromatography (eluent, hexane:ethyl acetate=2:1) to give 205 mg of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(4-methylphenyl)acrylamide (the present compound 1-4).

[0069] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.2(5H,m), 6.7-6.8(3H,m), 6.5(1H,s), 5.43(2H,d,J=53Hz), 3.87(3H,s), 3.85(3H,s), 3.62(2H,m), 2.84(2H,t), 2.34(3H,s)

[0070] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(3-methylphenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl) acrylamide, N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(3-methylphenyl)acrylamide (the present compound 1034) was obtained according to production example 1.

[0071] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.0-7.3(4H,m), 6.6-6.8(4H,m), 6.46(1H,br), 5.44(2H,d,J=53.4Hz), 3.86(3H,s), 3.85(3H,s), 3.6-3.7(2H,m), 2.84(2H,t,J=6.9Hz), 2.33(3H,s)

Production Example 2

[0072] Five hundred milligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide (1.46 mmol), 0.31 g (1.7 mmol) of 30% aqueous potassium hydroxide solution, 0.1 g (0.3 mmol) of tetrabutylammonium bromide and 10 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a small amount of 30% aqueous potassium hydroxide solution was further added, a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatograph analysis. Then, 5% hydrochrolic acid was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was washed with hexane to give 474 mg of N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide (the present compound 1005).

[0073] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.11-7.19(4H,m), 6.85(1H,s), 6.72-6.78 (3H,m), 6.36(1H,t,J=71.8Hz), 3.86(3H,s), 3.83(3H,s), 3.49(2H,m), 2.83(2H,t), 2.34(3H,s)

Production Example 3

[0074] One gram (1.00 g) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl) acrylamide (2.66 mmol), 130 mg (3.25 mmol) of 60% sodium hydride and 10 ml of anhydrous N,N-dimethylformamide were mixed and 0.46 g of bromofluoromethane was added thereto at −15° C. The mixture was stirred at −15° C. for 30 minutes and then stirred at 0° C. for 1 hour. The reaction mixture was added to water and extracted with ethyl acetate. The organic layer was washed with 5% hydrochloric acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel preparative thin layer chromatography (eluent, hexane:ethyl acetate=1:1) to give 100 mg of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(4-chlorophenyl)acrylamide (the present compound 1016).

[0075] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.0-7.3(4H,m), 6.5-6.8(5H,m), 5.41(2H,d, J=53.4Hz), 3.84(3H,s), 3.83(3H,s), 3.5-3.7(2H,m), 2.82(2H,t,J=6.9Hz)

Production Example 4

[0076] Five hundred milligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide (1.33 mmol), 2.00 g (3.56 mmol) of 10% aqueous potassium hydroxide solution, 87 mg (0.266 mmol) of tetrabutylammonium bromide and 10 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatograph analysis, 5% hydrochloric acid was added to the reaction mixture. The reaction mixture was extracted with ethyl acetate, washed with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) and the obtained residue was washed with hexane to give 360 mg of N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide.

[0077] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.4(4H,m), 6.7-6.9(4H,m), 6.35(1H,t, J=71.4Hz), 6.13(1H,br), 3.86(3H,s), 3.83(3H,s), 3.6-3.7(2H,m), 2.84(2H,t, J=6.8Hz)

Production Example 5

[0078] Five hundred miligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide (1.47 mmol), 0.11 g (1.47 mmol) of 3-chloropropyne and 5 ml of anhydrous N,N-dimethylformamide were mixed and 64 mg (1.61 mmol) of 60% sodium hydride was added thereto at 0-5° C. The mixture was stirred at 0-10° C. for 30 minutes and then stirred at room temperature. Water was added to the reaction mixture, followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=1:1) to give 180 mg of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-(2-propynyloxy)-2-(4-methylphenyl)acrylamide (the present compound 1182).

[0079] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.0-7.3(4H,m), 6.7-6.9(4H,m), 6.70(1H,s), 4.51(2H,d,J=2.4Hz), 3.86(6H,s), 3.5-3.7(2H,m), 2.83(2H,t,J=6.9Hz), 2.59(1H,t, J=2.4Hz), 2.32(3H,s)

[0080] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl) acrylamide, N-[2-(3,4-dimethoxyphenyl)ethyl]-3-(2-propynyloxy)-2-(4-chlorophenyl)acrylamide (the present compound 1185) was obtained according to production example 5.

[0081] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.60(1H,s), 7.2-7.4(4H,m), 7.0-7.1(2H,m), 6.73(1H,d,J=7.9Hz), 6.62(1H,d,J=1.9Hz), 6.56(1H,dd,J=8.0,1.9Hz), 5.28(1H,br), 4.52(2H,d,J=2.3Hz), 3.87(3H,s), 3.83(3H,s), 3.4-3.6(2H,m), 2.71(2H,t,J=6.9Hz), 2.57(1H,t,J=2.2Hz)

Production Example 6

[0082] 0.76 g (2.0 mmol) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide and 8ml of anhydrous N,N-dimethylformamide were mixed and 0.5 ml of bromofluoromethane was added thereto at −15° C. 88 mg (2.2 mmol) of 60% sodium hydride was added and stirred at −15° C. for 30 minutes and then stirred at approximately 0° C. for 1.5 hours. Water was added to the reaction mixture, followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel preparative thin layer chromatography (eluent, hexane:ethyl acetate=1:1) to give 0.68 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1103).

[0083] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.42(1H,br), 5.43(2H,d,J=53.7Hz), 3.85(3H,s), 3.84(3H,s), 3.6-3.7(2H,m), 2.83(2H,t,J=6.9Hz), 2.7-2.8(4H,m), 1.7-1.9(4H,m)

Production Example 7

[0084] A mixture of 380 mg (0.920 mmol) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 420 mg (1.01 mmol) of Lawesson's Reagent and 5 ml of anhydrous tetrahydrofuran was refluxed by heating for 3 hours. Water and ethyl acetate were added to the reaction mixture, and the ethyl acetate layer was washed with aqueous sodium hydroxide solution, aqueous ammonium chloride solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=3:1) to give 222 mg of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylthioamide (the present compound 1160).

[0085] 1 H-NMR(CDCl3, TMS) δ(ppm): 8.11(1H,s), 7.0-7.1(2H,m), 6.77(2H,d, J=6.0Hz), 6.70(1H,d,J=8.2Hz), 6.60(1H,d,J=1.7Hz), 6.55(1H,dd,J=7.9,1.9Hz), 5.48(2H,d,J=53.5Hz), 3.9-4.0(2H,m), 3.85(3H,s), 3.81(3H,s), 2.83(2H,t,J=6.7Hz), 2.6-2.8(4H,m), 1.7-1.9(4H,m)

[0086] By using 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-methylphenyl)acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-fluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-methylphenyl) acrylthioamide (the present compound 1445) was obtained according to production example 7.

[0087] 1 H-NMR(CDCl3, TMS) δ(ppm): 8.20(1H,s), 7.1-7.2(2H,m), 6.8-7.0(4H,m), 6.38(1H,t, J=71.0Hz), 6.5-6.6(1H,m), 4.74(2H,s), 3.9-4.0(2H,m), 3.79(3H,s), 2.83(2H,t,J=6.8Hz), 2.52(1H,t,J=2.1Hz), 2.39(3H,s)

Production Example 8

[0088] Five hundred milligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (1.31 mmol), 1.80 g (3.28 mmol) of 10% aqueous potassium hydroxide solution, 87 mg (0.262 mmol) of tetrabutylammonium bromide and 10 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. A sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatograph analysis. Then, 5% hydrochrolic acid was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =2:1) and the obtained residue was washed with hexane to give 350 mg of 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1104).

[0089] 1 H-NMR(CDCl3, TMS) δ(ppm): 6.9-7.1(3H,m), 6.7-6.9(4H,m), 6.36(1H,t, J=71.8Hz), 6.01(1H,br), 3.86(3H,s), 3.83(3H,s), 3.6-3.7(2H,m), 2.83(2H,t, J=6.9Hz), 2.6-2.8(4H,m), 1.7-1.9(4H,m)

[0090] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methoxyphenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2- (5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-methoxyphenyl)acrylamide (the present compound 1023) was obtained according to production example 8.

[0091] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.3(2H,m), 6.7-6.9(6H,m), 6.35(1H,t, J=71.7Hz), 6.04(1H,br), 3.86(3H,s), 3.82(3H,s), 3.80(3H,s), 3.6-3.7(2H,m), 2.83 (2H,t,J=6.8Hz)

[0092] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(naphthalen-2-yl)acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl) ethyl]-2-(naphthalen-2-yl)acrylamide (the present compound 2077) was obtained according to production example 8.

[0093] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.7-7.9(4H,m), 7.4-7.6(3H,m), 7.01(1H,s), 6.7-6.8(3H,m), 6.41(1H,t,J=71.6Hz), 6.08(1H,br), 3.84(3H,s), 3.79(3H,s), 3.6-3.7 (2H,m), 2.86(2H,t,J=6.9Hz)

[0094] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-bromophenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 2-(4-bromophenyl)-3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]acrylamide (the present compound 1020) was obtained according to production example 8.

[0095] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.4-7.5(2H,m), 7.1-7.2(2H,m), 6.89(1H,s), 6.7-6.9(3H,m), 6.35(1H,t,J=71.4Hz), 6.14(1H,br), 3.86(3H,s), 3.83(3H,s), 3.6-3.7 (2H,m), 2.84(2H,t,J=6.9Hz)

[0096] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-trifluoromethylphenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl) ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-trifluoromethylphenyl) acrylamide (the present compound 1029) was obtained according to production example 8.

[0097] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.4-7.6(4H,m), 6.95(1H,s), 6.7-6.9(3H,m), 6.37(1H,t,J=71.5Hz), 6.21(1H,br), 3.85(3H,s), 3.83(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.9Hz)

[0098] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(indan-5-yl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl) ethyl]-2-(indan-5-yl)acrylamide (the present compound 1122) was obtained according to production example 8.

[0099] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.0-7.2(3H,m), 6.6-6.9(4H,m), 6.35(1H,t, 71.7Hz), 6.02(1H,br), 3.85(3H,s), 3.83(3H,s), 3.6-3.7(2H,m), 2.8-3.0(6H,m), 2.0-2.1(2H,m)

[0100] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2- (4-nitrophenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl) ethyl]-2-(4-nitrophenyl)acrylamide (the present compound 1247) was obtained according to production example 8.

[0101] 1 H-NMR(CDCl3, TMS) δ(ppm): 8.1-8.2(2H,m), 7.4-7.5(2H,m), 7.03(1H,s), 6.6-6.9(3H,m), 6.37(1H,t,J=70.8Hz), 6.28(1H,br), 3.8-3.9(6H,m), 3.6-3.7(2H,m), 2.86(2H,t,J=6.7Hz)

[0102] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylthiophenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-methylthiophenyl)acrylamide (the present compound 1026) was obtained according to production example 8.

[0103] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.20(4H,s), 6.7-6.9(4H,m), 6.36(1H,t, J=71.5Hz), 6.07(1H,br), 3.86(3H,s), 3.82(3H,s), 3.6-3.7(2H,m), 2.84(2H,t, J=6.9Hz), 2.49(3H,s)

[0104] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(3,4-dichlorophenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 2-(3,4-dichlorophenyl)-3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]acrylamide (the present compound 1065) was obtained according to production example 8.

[0105] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.3-7.5(2H,m), 7.14(1H,dd,J=8.5,2.1Hz), 6.90(1H,s), 6.7-6.9(3H,m), 6.35(1H,t,J=71.4Hz), 6.21(1H,br), 3.87(3H,s), 3.86(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8Hz)

[0106] By using N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-isopropylphenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-isopropylphenyl)acrylamide (the present compound 1251) was obtained according to production example 8.

[0107] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.0-7.2(4H,m), 6.7-6.9(4H,m), 6.38(1H,t, J=71.7Hz), 6.05(1H,br), 3.86(3H,s), 3.83(3H,s), 3.5-3.7(2H,m), 2.8-3.0(3H,m), 1.23(6H,d, J=6.8Hz)

[0108] By using N-[3-(3,4-dimethoxyphenyl)propyl]-3-hydroxy-2-(4-methylphenyl) acrylamide in place of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 3-difluoromethoxy-N-[3-(3,4-dimethoxyphenyl)propyl]-2-(4-methylphenyl)acrylamide (the present compound 1476) was obtained according to production example 8.

[0109] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.3(4H,m), 6.87(1H,s), 6.7-6.8(3H,m), 6.46(1H,t,J=72.1Hz), 5.98(1H,br), 3.86(3H,s), 3.85(3H,s), 3.4-3.5(2H,m), 2.63(2H,t, J=7.43Hz), 2.34(3H,s), 1.8-2.0(2H,m)

Production Example 9

[0110] Five hundred milligrams (500 mg) of 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl) ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (1.16 mmol) and 5 ml of anhydrous N,N-dimethylformamide were mixed and cooled, and then 49 mg (1.22 mmol) of 60% sodium hydride was added thereto and stirred at 0° C. for 30 minutes. To the mixture, 164 mg (1.16 mmol) of methyl iodide was added and stirred at 0° C. for 30 minutes and then at room temperature for 2 hours. Water was added to the reaction mixture, which which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel preparative thin layer chromatography (eluent, hexane:ethyl acetate =3:1) to give 460 mg of 3-difluoromethoxy-N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1125).

[0111] 1 H-NMR(CDCl3, TMS) δ(ppm): 6.5-7.1(7H,m), 6.38(1H,t,J=72.4Hz), 3.85 (3H,s), 3.82(3H,s), 3.7-3.8(2H,m), 2.8-3.0(5H,m), 2.6-2.8(4H,m), 1.7-1.9(4H,m)

Production example 10

[0112] Six hundred milligrams (600 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (1.57 mmol), 0.14 g (1.89 mmol) of 3-chloropropyne, 280 mg (2.05 mmol) of potassium carbonate and 10 ml of anhydrous N,N-dimethylformamide were mixed and stirred at room temperature. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =1:1) to give 415 mg of N-[2-(3,4-dimethoxyphenyl) ethyl]-3-(2-propynyloxy)-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1196).

[0113] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.69(1H,s), 4.50(2H,d,J=2.4Hz), 3.86(6H,s), 3.5-3.7(2H,m), 2.7-2.9(6H,m), 2.61(1H,t, J=2.4Hz), 1.7-1.9(4H,m)

[0114] By using 1,1,3-trichloropropene in place of 3-chloropropyne, 3-(3,3-dichloroallyloxy)-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1232) was obtained according to production example 10.

[0115] 1 H-NMR(CDCl3, TMS) δ(ppm): 6.9-7.0(3H,m), 6.7-6.9(4H,m), 6.53(1H,s), 5.98(1H,d,J=6.4Hz), 4.51(2H,d,J=6.5Hz), 3.86(3H,s), 3.85(3H,s), 3.6-3.7(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

[0116] By using 1-chloro-2-fluoroethane in place of 3-chloropropyne, N-[2-(3,4-dimethoxyphenyl) ethyl]-3-(2-fluoroethoxy)-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide (the present compound 1241) was obtained according to production example 10.

[0117] 1 H-NMR(CDCl3, TMS) δ(ppm): 6.99(3H,s), 6.93(1H,br), 6.7-6.9(3H,m), 6.60(1H,s), 4.4-4.7(2H,m), 4.0-4.2(2H,m), 3.86(6H,s), 3.6-3.7(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

Production Example 11

[0118] Three hundred milligrams (300 mg) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-(2-propynyloxy)-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (0.716 mmol), 20 mg (0.0766 mmol) of tetrabutylammonium fluoride, 100 mg (0.716 mmol) of potassium carbonate and 2 ml of carbon tetrachloride were mixed and stirred at room temperature. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =1:1) to give 140 mg of 3-(3-chloro-2-propynyloxy)-N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1223).

[0119] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.65(1H,s), 4.50(2H,d,J=2.6Hz), 3.86(6H,s), 3.5-3.7(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

Production Example 12

[0120] 239 mg of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (0.572 mmol), 128 mg (1.72 mmol) of 3-chloropropyne, 3 ml of anhydrous N,N-dimethylformamide and 20 mg (0.50 mmol) of 60% sodium hydride were mixed and stirred at room temperature for 4 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 225 mg of 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1268).

[0121] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.69(1H,s), 4.50(2H,d, J=2.4Hz), 3.86(6H,s), 3.5-3.7(2H,m), 2.7-2.9(6H,m), 2.61(1H,t, J=2.4Hz), 1.7-1.9(4H,m)

[0122] By using bromoethane in place of 3-chloropropyne, 3-difluoromethoxy-N-[2-(4-ethoxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide (the present compound 1143) was obtained according to production example 12.

[0123] 1 H-NMR(CDCl3, TMS) δ(ppm): 6.99(3H,s), 6.7-6.9(4H,m), 6.37(1H,t,J=71.8Hz), 6.12(1H,br), 4.06(2H,q,J=8.1Hz), 3.80(3H,s), 3.5-3.7(2H,m), 2.6-2.9(6H,m), 1.7-1.9(4H,m), 1.44(3H,t,J=7.0Hz)

[0124] By using chloropropane in place of 3-chloropropyne, 3-difluoromethoxy-N-[2-(3-methoxy-4-propoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide (the present compound 1258) was obtained according to production example 12.

[0125] 1 H-NMR(CDCl3, TMS) δ(ppm): 6.9-7.1(3H,m), 6.4-6.9(4H,m), 6.36(1H,t, J=71.9Hz), 6.05(1H,br), 3.97(2H,t,J=6.8Hz), 3.82(3H,s), 3.5-3.7(2H,m), 2.6-2.9 (6H,m), 1.7-1.9(6H,m), 1.03(3H,t,J=7.4Hz)

[0126] By using chloroacetonitrile in place of 3-chloropropyne, N-[2-(4-cyanomethoxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1274) was obtained according to production example 12.

[0127] 1 H-NMR(CDCl3, TMS) δ(ppm): 6.9-7.1(4H,m), 6.7-6.9(3H,m), 6.39(1H,t, J=71.8Hz), 6.10(1H,br), 4.79(2H,s), 3.83(3H,s), 3.6-3.7(2H,m), 2.6-2.9(6H,m), 1.7-1.9(4H,m)

[0128] By using allyl chloride in place of 3-chloropropyne, N-[2-(4-allyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1266) was obtained according to production example 12.

[0129] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.00(3H,s), 6.6-6.9(4H,m), 6.35(1H,t, J=71.9Hz), 5.9-6.2(2H,m), 5.2-5.5(2H,m), 4.58(2H,dd,J=3.9,1.3Hz), 3.83(3H,s), 3.5-3.7(2H,m), 2.6-2.9(6H,m), 1.7-1.9(4H,m)

[0130] By using 1-chloro-2-butyne in place of 3-chloropropyne, N-[2-{4-(2-butynyloxy)-3-methoxyphenyl}ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1269) was obtained according to production example 12.

[0131] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.00(3H,s), 6.9-7.0(1H,m), 6.84(1H,s), 6.7-6.8(2H,m), 6.34(1H,t,J=71.7Hz), 6.03(1H,br), 4.69(2H,q,J=2.3Hz), 3.82(3H,s), 3.6-3.7(2H,m), 2.83(2H,t,J=6.9Hz), 2.7-2.8(4H,m), 1.83(3H,t,J=2.2Hz), 1.7-1.8(4H,m)

[0132] By using methoxymethyl chloride in place of 3-chloropropyne, 3-difluoromethoxy-N-[2-(3-methoxy-4-methoxymethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1284) was obtained according to production example 12.

[0133] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.0-7.1(4H,m), 6.85(1H,s), 6.7-6.8(2H,m), 6.34(1H,t,J=71.6Hz), 6.02(1H,br), 5.20(2H,s), 3.83(3H,s), 3.6-3.7(2H,m), 3.51(3H,s), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

[0134] By using isopropyl chloride in place of 3-chloropropyne, 3-difluoromethoxy-N-[2-(4-isopropoxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide (the present compound 1259) was obtained according to production example 12.

[0135] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.00(3H,s), 6.6-6.9(4H,m), 6.35(1H,t, J=71.7Hz), 6.02(1H,br), 4.4-4.6(1H,m), 3.80(3H,s), 3.6-3.7(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m), 1.35(6H,d,J=6.1Hz)

Production Example 13

[0136] Eighty milligrams (80 mg) of acetyl chloride (1.00 mmol) were added to a mixture of 420 mg (1.00 mmol), of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide, 120 mg (1.20 mmol) of triethylamine and 5 ml of tetrahydrofuran at 0° C. and stirred at 0° C. for 30 minutes and then at room temperature for 2 hours. Water and ethyl acetate were added to the reaction mixture. The organic layer was washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =3:1) to give 260 mg of 3-difluoromethoxy-N-[2-(3-methoxy-4-acetyloxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1282).

[0137] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.01(3H,s), 6.7-7.0(4H,m), 6.34(1H,t, J=71.2Hz), 6.18(1H,br), 3.77(3H,s), 3.6-3.7(2H,m), 2.83(2H,t,J=6.7Hz), 2.7-2.8 (4H,m), 2.30(3H,s), 1.7-1.8(4H,m)

Production example 14

[0138] One and a half grams (1.5 g) of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide (4.39 mmol), 193 mg (4.83 mmol) of 60% sodium hydride, 10 ml of anhydrous dimethoxyethane and 10 ml of anhydrous diethyl ether were mixed, 0.8 ml of dibromodifluoromethane was added thereto at 0° C. and stirred at 0° C. for 3 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with water, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 1.0 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-bromodifluoromethoxy-2-(4-methylphenyl)acrylamide (the present compound 1197).

[0139] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.2(4H,m), 6.7-6.8(4H,m), 6.4(1H,s), 3.86(3H,s), 3.83(3H,s), 3.66(2H,m), 2.84(2H,t), 2.35(3H,s)

Production Example 15

[0140] Five hundred hundred milligrams (500 mg) of N-[2-(3,4-dimethoxyphenyl) ethyl]-3-bromodifluoromethoxy-2-(4-methylphenyl)acrylamide (1.06 mmol), 0.5 ml of hydrogen fluoride-pyridine complex, 340 mg (1.57 mmol) of mercury oxide and 1 ml of isopropyl ether were mixed and stirred at room temperature for 2 hours. Aqueous sodium bicarbonate solution and celite were added to the reaction mixture and filtered. Water was added to the filtrate, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from t-butyl methyl ether and hexane to give 0.35 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-trifluoromethoxy-2-(4-methylphenyl) acrylamide (the present compound 1006).

[0141] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.2(4H,m), 6.7-6.8(3H,m), 6.71(1H,s), 6.1(1H,s), 3.84(3H,s), 3.82(3H,s), 3.62(2H,m), 2.89(2H,t), 2.32(3H,s)

Production Example 16

[0142] 4.20 g (9.19 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 14.3 g (23.0 mmol) of 10% aqueous potassium hydroxide solution, 0.60 g (1.84 mmol) of tetrabutylammonium bromide and 40 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatography, 5% hydrochloric acid was added to the reaction mixture. The reaction mixture was extracted with ethyl acetate, washed with 5% hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =2:1) and the obtained product was washed with hexane to give 2.4 g of N-[2-(4-benzyloxy-3-methoxyphenyl) ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1281).

[0143] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.5(5H,m), 6.9-7.1(3H,m), 6.6-6.9(4H, m), 6.26(1H,t,J=71.6Hz), 6.02(1H,br), 5.13(2H,s), 3.84(3H,s), 3.5-3.7(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

[0144] By using N-[2-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide in place of N-[2-(4-benzyloxy-3-methoxyphenyl) ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide, 3-difluoromethoxy-N-[2-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1450) was obtained according to production example 16.

[0145] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.01(3H,s), 6.85(1H,s), 6.6-6.8(3H,m), 6.41(1H, t,J=71.6Hz), 6.02(1H,br), 4.24(4H,s), 3.5-3.7(2H,m), 2.7-2.8(6H,m), 1.7-1.9(4H,m)

[0146] By using N-[2-(3-chloro-4-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide in place of N-[2-(4-benzyloxy-3-methoxyphenyl) ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide, N-[2-(3-chloro-4-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1447) was obtained according to production example 16.

[0147] 1 H-NMR(CDCl3, TMS) δ(ppm): 6.9-7.2(4H,m), 6.8-6.9(3H,m), 6.40(1H,t, J=71.6Hz), 6.00(1H,br), 3.88(3H,s), 3.5-3.6(2H,m), 2.7-2.9(6H,m), 1.7-1.9(4H,m)

[0148] By using N-[2-(4-methoxy-3-methylphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide in place of N-[2-(4-benzyloxy-3-methoxyphenyl) ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide, 3-difluoromethoxy-N-[2-(4-methoxy-3-methylphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1448) was obtained according to production example 16.

[0149] 1 H-NMR(CDCl3, TMS) δ(ppm): 6.9-7.0(4H,m), 6.7-6.9(3H,m), 6.34(1H,t, J=71.7Hz), 6.00(1H,br), 3.81(3H,s), 3.5-3.7(2H,m), 2.7-2.8(6H,m), 2.17(3H,s), 1.7-1.9(4H,m)

Production Example 17

[0150] 2.40 g (4.73 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 1.20 g (7.09 mmol) of 48% hydrobromic acid and 30 ml of acetic acid were mixed and stirred at 80° C. for 2 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =1:1) to give 1.81 g of 3-difluoromethoxy-N- [2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1371).

[0151] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.0-7.1(3H,m), 6.84(1H,d,J=3.3Hz), 6.80(1H,s), 6.6-6.7(2H,m), 6.36(1H,t,J=71.8Hz), 6.12(1H,br), 5.78(1H,s), 3.82(3H,s), 3.5-3.7(2H,m), 2.4-2.8(6H,m), 1.7-1.9(4H,m)

Production Example 18

[0152] 417 mg (1.00 mmol) of 3-difluoromethoxy-N-[2-(3-hydroxy-4-methoxyphenyl) ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, 5 ml of anhydrous N,N-dimethylformamide, 74 mg (1.00 mmol) of 3-chloropropyne and 50 mg (1.25 mmol) of 60% sodium hydride were mixed and stirred at room temperature for 3 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography to give 162 mg of 3- difluoromethoxy-N-[2-{4-methoxy-3-(2-propynyloxy)phenyl}ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1299).

[0153] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.00(3H,s), 6.8-6.9(4H,m), 6.37(1H,t, J=71.7Hz), 6.03(1H,br), 4.71(2H,d,J=2.4Hz), 3.85(3H,s), 3.6-3.7(2H,m), 2.83(2H, t,J=6.8Hz), 2.7-2.8(4H,m), 2.47(1H,t,J=2.4Hz), 1.7-1.9(4H,m)

[0154] By using bromoethane in place of 3-chloropropyne, 3-difluoromethoxy-N-[2-(3-ethoxy-4-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide (the present compound 1320) was obtained according to production example 18.

[0155] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.36(1H,t, J=71.7Hz), 6.02(1H,br), 4.04(2H,q,J=7.0Hz), 3.84(3H,s), 3.5-3.7(2H,m), 2.7-2.9 (6H,m), 1.7-1.9(4H,m), 1.44(3H,t,J=7.0Hz)

[0156] By using chloroacetonitrile in place of 3-chloropropyne, N-[2-(3-cyanomethoxy-4-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (the present compound 1305) was obtained according to production example 18.

[0157] 1 H-NMR(CDCl3, TMS) δ(ppm): 6.8-7.1(7H,m), 6.40(1H,t,J=72.1Hz), 6.05(1H,br), 4.77(2H,s), 3.86(3H,s), 3.5-3.7(2H,m), 2.84(2H,t,J=6.9Hz), 2.7-2.8(4H,m), 1.7-1.9(4H,m)

Production Example 19

[0158] Five hundred milligrams (500 mg) of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide (1.33 mmol), 5 ml of anhydrous N,N-dimethylformamide, 196 mg (2.65 mmol) of 3-chloropropyne and 60 mg (1.46 mmol) of 60% sodium hydride were stirred at room temperature for 2 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 242 mg of 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy) phenyl}ethyl]-2-(4-methylphenyl)acrylamide (the present compound 1353).

[0159] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.2(4H,m), 6.95(1H,d,J=8.25Hz), 6.85(1H,s), 6.7-6.8(2H,m), 6.35(1H,t,J=71.7Hz), 6.11(1H,br), 4.73(2H,d,J=2.3Hz), 3.81(3H,s), 3.6-3.7(2H,m), 2.83(2H,t,J=6.9Hz), 2.49(1H,d,J=2.4Hz), 2.32(3H,s)

[0160] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(indan-5-yl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-2-(indan-5-yl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide (the present compound 1360) was obtained according to production example 19.

[0161] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.0(2H,m), 6.9-7.1(2H,m), 6.85(1H,s), 6.7-6.8(2H,m), 6.35(1H,t,J=71.6Hz), 6.06(1H,br), 4.74(2H,d,J=2.4Hz), 3.83(3H,s), 3.6-3.7(2H,m), 2.8-2.9(6H,m), 2.49(1H,t,J=2.4Hz), 2.0-2.2(2H,m)

[0162] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methoxyphenyl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-2-(4-methoxyphenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide (the present compound 1358) was obtained according to production example 19.

[0163] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.3(2H,m), 6.7-7.0(6H,m), 6.34(1H,t,J=71.6Hz), 6.05(1H,br), 4.74(2H,d,J=2.5Hz), 3.83(3H,s), 3.81(3H,s), 3.6-3.7(2H,m), 2.84(2H,t,J=6.8Hz), 2.49(1H,t,J=2.5Hz)

[0164] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-phenylacrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3- difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-phenylacrylamide (the present compound 1388) was obtained according to production example 19.

[0165] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.3-7.4(5H,m), 6.96(1H,d,J=8.7Hz), 6.90(1H,s), 6.7-6.8(2H,m), 6.36(1H,t,J=71.5Hz), 6.07(1H,br), 4.75(2H,d,J=2.4Hz), 3.83(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8Hz), 2.50(1H,t,J=2.4Hz)

[0166] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-trifluoromethylphenyl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-trifluoromethylphenyl)acrylamide (the present compound 1357) was obtained according to production example 19.

[0167] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.59(2H,d,J=8.2Hz), 7.43(2H,d,J=8.0Hz), 6.9-7.0(2H,m), 6.7-6.8(2H,m), 6.35(1H,t,J=71.0Hz), 6.21(1H,br), 4.75(2H,d, J=2.2Hz), 3.84(3H,s), 3.6-3.7(2H,m), 2.87(2H,t,J=6.8Hz), 2.49(1H,t,J=2.2Hz)

[0168] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-ethylphenyl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-2-(4-ethylphenyl)-N-[2-{3-methoxy-4- (2-propynyloxy)phenyl}ethyl]acrylamide (the present compound 1354) was obtained according to production example 19.

[0169] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.3(4H,m), 6.96(1H,d,J=8.7Hz), 6.87 (1H,s), 6.7-6.8(2H,m), 6.35(1H,t,J=71.6Hz), 6.06(1H,br), 4.75(2H,d,J=2.4Hz), 3.83(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8Hz), 2.64(2H,q,J=6.8Hz), 2.50(1H,t, J=2.4Hz)

[0170] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-fluorophenyl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-2-(4-fluorophenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide (the present compound 1392) was obtained according to production example 19.

[0171] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.3(2H,m), 6.9-7.1(3H,m), 6.87(1H,s), 6.7-6.8(2H,m), 6.34(1H,t,J=71.3Hz), 6.17(1H,br), 4.76(2H,d,J=2.4Hz), 3.85(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8Hz), 2.64(2H,q,J=6.8Hz), 2.50(1H,t,J=2.4Hz)

[0172] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(naphthalen-2-yl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(naphthalen-2-yl)acrylamide (the present compound 2202) was obtained according to production example 19.

[0173] 1 H- NMR(CDCl3, TMS) δ(ppm): 7.7-7.9(4H,m), 7.4-7.5(3H,m), 7.02(1H,s), 6.93(1H,d,J=8.6Hz), 6.7-6.8(2H,m), 6.39(1H,t,J=71.5Hz), 6.11(1H,br), 4.72(2H,d, J=2.2Hz), 3.78(3H,s), 3.6-3.7(2H,m), 2.87(2H,t,J=6.8Hz), 2.48(1H,t,J=2.5Hz)

[0174] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(5-methylthiophen-2-yl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-2-(5-methylthiophen-2-yl)-N-[2-{3-methoxy-4-(2-propynyloxy) phenyl}ethyl]acrylamide (the present compound 2133) was obtained according to production example 19.

[0175] 1 H-NMR(CDCl3, TMS) δppm): 7.62(1H,s), 6.95(1H,d,J=8.6Hz), 6.15-6.72 (3H,m), 6.4(1H,br), 4.74(2H,d,J=2.4Hz), 3.83(3H,s), 3.6(2H,m), 2.79(2H,t, J=6.9Hz), 2.50(1H,t,J=2.4Hz), 2.47(3H,s)

[0176] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(3,4-dichlorophenyl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-2-(3,4-dichlorophenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]acrylamide (the present compound 1429) was obtained according to production example 19.

[0177] 1 H-NMR(CDCl3, TMS) δppm): 7.4-7.5(2H,m), 7.13(1H,dd,J=2.14, 8.2Hz), 6.97(1H,d,J=7.1Hz), 6.92(1H,s), 6.7-6.8 (2H,m), 6.0-6.7(2H,m), 4.75(2H,d,J=2.4Hz), 3.84(3H,s), 3.6(2H,m), 2.85(2H,t, J=6.5Hz), 2.51(1H,t,J=2.4Hz)

[0178] By using 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)-1-methylethyl]-2-(4-methylphenyl)acrylamide in place of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acrylamide, 3-difluoromethoxy-N-[2-(3-methoxy-4-(2-propynyloxy)phenyl)-1-methylethyl]-2-(4-methylphenyl) acrylamide (the present compound 1465) was obtained according to production example 19.

[0179] 1 H-NMR(CDCl3, TMS) δppm): 7.1-7.2(4H,m), 6.95(1H,d,J=7.9Hz), 6.85(1H,s), 6.7-6.8 (2H,m), 6.36(1H,t,J=71.7Hz), 5.78(1H,d,J=7.8Hz), 4.75(2H,d,J=2.2Hz), 4.3-4.5(1H,m), 3.82(3H,s), 2.7-2.9(2H,m), 2.49(1H,t, J=2.1Hz), 2.34(3H,s), 1.20(3H,d,J=6.7Hz)

[0180] By using bromomethylcyclopropane in place of 3-chloropropyne, N-[2-(4-cyclopropylmethoxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-methylphenyl) acrylamide (the present compound 1271) was obtained according to production example 19.

[0181] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.2(4H,m), 6.7-6.9(4H,m), 6.35(1H,t, J=71.7Hz), 6.01(1H,br), 3.8-3.9(5H,m), 3.6-3.7(2H,m), 2.82(2H,t, J=6.8Hz), 2.33(3H,s), 1.2-1.4(1H,m), 0.6-0.7(2H,m), 0.3-0.4(2H,m)

Production Example 20

[0182] 477 mg (1.20 mmol) of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-chlorophenyl)acrylamide, 5 ml of anhydrous N,N-dimethylformamide, 180 mg (2.40 mmol) of 3-chloropropyne and 72 mg (1.80 mmol) of 60% sodium hydride were stirred at room temperature for 2 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 70 mg of 3-difluoromethoxy-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-2-(4-chlorophenyl) acrylamide (the present compound 1355).

[0183] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.4(4H,m), 6.97(1H,d,J=8.7Hz), 6.89 (1H,s), 6.7-6.8(2H,m), 6.34(1H,t,J=71.3Hz), 6.17(1H,br), 4.75(2H,d,J=2.4Hz), 3.84(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=7.0Hz), 2.50(1H,d,J=2.4Hz)

Production Example 21

[0184] Two hundred milligrams (200 mg) of 3-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide (0.611 mmol), 2 ml of anhydrous N,N-dimethylformamide, 144 mg (1.22 mmol) of 3-bromopropyne and 173 mg (1.25 mmol) of potassium carbonate were stirred at room temperature for 2 hours and then at 50° C. for 4 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =1:1) to give 100 mg of N-[2-{3-methoxy-4-(2-propynyloxy) phenyl}ethyl]-3-(2-propynyloxy)-2-(4-methylphenyl)acrylamide (the present compound 1364).

[0185] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.2(4H,m), 6.98(1H,d,J=8.6Hz), 6.6-6.9(4H,m), 4.74(2H,d,J=2.5Hz), 4.49(2H,d,J=2.5Hz), 3.85(3H,s), 3.6-3.7 (2H,m), 2.83(2H,t,J=6.9Hz), 2.59(1H,d,J=2.3Hz), 2.50(1H,d,J=2.2Hz), 2.32(3H,s)

Production Example 22

[0186] Three hundred milligrams (300 mg) of 3-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-chlorophenyl)acrylamide (0.863 mmol) and 3 ml of anhydrous N,N-dimethylformamide were mixed and 320 mg (4.32 mmol) of 3-chloropropyne was added thereto at 0-5° C., and then 100 mg (2.59 mmol) of 60% sodium hydride was added at 0-5° C. The mixture was stirred for 1 hour at 0-5° C. and further at room temperature. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =2:1) to give 160 mg of 2-(4-chlorophenyl)-N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-(2-propynyloxy) acrylamide (the present compound 1367).

[0187] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.3(4H,m), 6.9-7.0(2H,m), 6.7-6.8 (3H,m), 4.75(2H,d,J=2.4Hz), 4.52(2H,d,J=2.4Hz), 3.86(3H,s), 3.6-3.7(2H,m), 2.84(2H,t,J=6.9Hz), 2.63(1H,d,J=2.4Hz), 2.51(1H,d,J=2.42Hz)

Production Example 23

[0188] 4.17 g (10.00 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide, 22.4 g (40.0 mmol) of 10% aqueous potassium hydroxide solution, 1.62 g (5.00 mmol) of tetrabutylammonium bromide and 50 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatography, 5% hydrochloric acid was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was washed with diethyl ether to give 3.46 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide (the present compound 1451).

[0189] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.5(5H,m), 7.1-7.2(4H,m), 6.84(1H,s), 6.80(1H,d,J=8.2Hz), 6.74(1H,d,J=1.6Hz), 6.65(1H,dd,J=8.0,1.8Hz), 6.26(1H,t, J=71.6Hz), 6.02(1H,br), 5.13(2H,s), 3.84(3H,s), 3.6-3.7(2H,m), 2.81(2H,t, J=6.8Hz), 2.33(3H,s)

Production Example 24

[0190] 9.40 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide (20.1 mmol), 3.72 g (22.1 mmol) of 48% hydrobromic acid and 95 ml of acetic acid were mixed and stirred at 80° C. for 1.5 hours. The solvent was distilled off from the reaction mixture under reduced pressure and the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 4.55 g of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide (the present compound 1452).

[0191] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.2(4H,m), 6.8-6.9(2H,m), 6.6-6.7(2H,m), 6.35(1H,t,J=71.7Hz), 6.02(1H,br), 5.51(1H,s), 3.84(3H,s), 3.6-3.7(2H,m), 2.81(2H,t, J=6.9Hz), 2.34(3H,s)

Production Example 25

[0192] 1.48 g (3.38 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide, 4.3 g (8.46 mmol) of 10% aqueous potassium hydroxide solution, 220 mg (0.677 mmol) of tetrabutylammonium bromide and 15 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatography, 5% hydrochloric acid was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated aqueous sodium bicarbonate solution and saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was washed with hexane to give 1.45 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl)-3-difluoromethoxyacrylamide (the present compound 1453).

[0193] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.5(9H,m), 6.87(1H,s), 6.80(1H,d, J=8.3Hz), 6.75(1H,d,J=2.0Hz), 6.66(1H,dd,J=8.0,2.0Hz), 6.23(1H,t,J=71.7Hz), 6.12(1H,br), 5.14(2H,s), 3.85(3H,s), 3.6-3.7(2H,m), 2.82(2H,t,J=6.8Hz)

Production Example 26

[0194] 1.45 g (2.97 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl)-3-difluoromethoxyacrylamide, 751 mg (4.46 mmol) of 48% hydrobromic acid and 15 ml of acetic acid were mixed and stirred at 80° C. for 1.5 hours. Water was added to to the reaction mixture, which was followed by extracted with ethyl acetate twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =1:1) to give 880 mg of 2-(4-chlorophenyl)-3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]acrylamide (the present compound 1454).

[0195] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.4(4H,m), 6.88(1H,s), 6.84(1H,d, J=7.8Hz), 6.6-6.8(2H,m), 6.34(1H,t,J=71.4Hz), 6.14(1H,br), 5.53(1H,s), 3.85 (3H,s), 3.6-3.7(2H,m), 2.82(2H,t,J=6.8Hz)

Reference Production Example 1

[0196] A mixture of 5.00 g (33.3 mmol) of (4-methylphenyl)acetic acid, 5.94 g (49.9 mmol) of thionyl chloride, 0.12 g (1.6 mmol) of N,N-dimethylformamide and 20 ml of toluene was stirred at 100° C. for 1 hour, cooled and concentrated under reduced pressure. The residue was added to a mixture of 6.34 g (35.0 mmol) 2-(3,4-dimethoxyphenyl)ethylamine, 8.6 g (67 mmol) of diisopropylethylamine and 25 ml of toluene at 0° C. and kept at 0° C. for 30 minutes and at room temperature for 6 hours. Water and ethyl acetate were added to the reaction mixture and precipitated solid was collected with filtration. The obtained solid was dried to give 5.76 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-methylphenyl)acetamide.

[0197] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.0-7.2(4H,m), 6.72(1H,d,J=8.2Hz), 6.57-6.60(2H, m), 5.4(1H,s), 3.86(3H,s), 3.82(3H,s), 3.49(2H,s), 3.43(2H,m), 2.67(2H,t,J=6.9Hz), 2.34(3H,s)

[0198] One gram (1.0 g) of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-methylphenyl) acetamide (3.2 mmol), 1.68 g (9.64 mmol) of t-butoxybis(dimethylamino)methane and 15 ml of N,N-dimethylformamide were mixed and stirred at 90° C. for 3 hours and then at 110° C. for 3 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure to give 1.20 g of crude N-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2- (4-methylphenyl)acrylamide.

[0199] One gram (1.0 g) of crude N-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(4-methylphenyl)acrylamide (2.7 mmol), 12 ml of 5% hydrochloric acid and 20 ml of tetrahydrofuran were mixed and stirred at room temperature for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 0.76 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide.

[0200] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.26(1H,s), 7.0-7.1(4H,m), 6.6-6.7(3H,m), 5.5(1H,s), 3.86(3H,s), 3.82(3H,s), 3.51(2H,m), 2.75(2H,t,J=6.9Hz), 2.35(3H,s)

Reference Production Example 2

[0201] A mixture of 5.00 g (29.3 mmol) of (4-chlorophenyl)acetic acid, 5.23 g (43.9 mmol) of thionyl chloride and 50 ml of toluene was stirred at 50° C. for 30 minutes and then 80° C. for 2.5 hours, cooled and concentrated under reduced pressure. The residue was added to a mixture of 5.18 g (28.5 mmol) 2-(3,4-dimethoxyphenyl)ethylamine, 3.46 g (34.2 mmol) of triethylamine and 50 ml tetrahydrofuran at 0° C. and kept at 0° C. for 30 minutes and at room temperature for 3 hours. Water and ethyl acetate were added to the reaction mixture and precipitated solid was collected with filtration. The obtained solid was dried to give 5.75 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-chlorophenyl) acetamide.

[0202] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.3(2H,m), 7.0-7.1(2H,m), 6.72(1H,d, J=8.1Hz), 6.61(1H,d,J=2.0Hz), 6.51(1H,dd,J=8.0,1.9Hz), 5.31(1H,br), 3.87(3H,s), 3.83(3H,s), 3.4-3.5(4H,m), 2.68(2H,t,J=6.8Hz)

[0203] 5.75 g (17.2 mmol) of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(4-chlorophenyl) acetamide, 9.00 g (51.6 mmol) of t-butoxybis(dimethylamino)methane and 90 ml of N,N-dimethylformamide were mixed and stirred at 90° C. for 3 hours and then at 110° C. for 3 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure to give 6.68 g of crude N-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(4-chlorophenyl)acrylamide.

[0204] 6.60 g (17.2 mmol) of crude N-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(4-chlorophenyl)acrylamide, 80 ml of 5% hydrochloric acid and 100 ml of tetrahydrofuran were mixed and stirred at room temperature for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 4.46 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide.

[0205] 1 H-NMR(CDCl3, TMS) δ(ppm): 13.66(1H,d,J=11.34Hz), 7.2-7.3(2H,m), 7.0-7.1(3H,m), 6.74(1H,d,J=8.1Hz), 6.5-6.6(2H,m), 5.32(1H,br), 3.87(3H,s), 3.80(3H,s), 3.5-3.6(2H,m), 2.75(2H,d,J=6.8Hz)

Reference Production Example 3

[0206] According to the description of JP hei10-87602A, (5,6,7,8-tetrahydronaphthalen-2-yl)acetic acid was obtained.

[0207] A mixture of 3.60 g (18.9 mmol) of (5,6,7,8-tetrahydronaphthalen-2-yl)acetic acid, 3.38 g (28.4 mmol) of thionyl chloride and 40 ml of toluene was stirred at 50° C. for 30 minutes and then 80° C. for 2.5 hours, cooled and concentrated under reduced pressure. The residue was added to a mixture of 3.43 g (18.9 mmol) 2-(3,4-dimethoxyphenyl)ethylamine, 2.30 g (22.7 mmol) of triethylamine and 40 ml of tetrahydrofuran at 0° C. and kept at 0° C. for 30 minutes and at room temperature for 3 hours. Water and ethyl acetate were added to the reaction mixture and precipitated solid was collected with filtration. The obtained solid was dried to give 5.78 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acetamide.

[0208] 1 H-NMR(CDCl3, TMS) δ(ppm): 6.99(1H,d,J=8.1Hz), 6.8-6.9(2H,m), 6.5-6.8(3H,m), 5.42(1H,br), 3.85(3H,s), 3.82(3H,s), 3.4-3.5(4H,m), 2.6-2.8(6H,m), 1.7-1.9(4H,m)

[0209] 2.65 g (7.50 mmol) of N-[2-(3,4-dimethoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acetamide, 3.92 g (22.5 mmol) of t-butoxybis (dimethylamino)methane and 30 ml of N,N-dimethylformamide were mixed and stirred at 90° C. for 3 hours and then at 110° C. for 3 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure to give 3.30 g of crude N-[2-(3,4-dimethoxyphenyl) ethyl]-3-dimethylamino-2-(5,6,7,8-tetrahydronaphthalen-2-yl) acrylamide.

[0210] Three grams (3.00 g) of crude N-[2-(3,4-dimethoxyphenyl)ethyl]-3-dimethylamino-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide (7.35 mmol), 30 ml of 5% hydrochloric acid and 30 ml of tetrahydrofuran were mixed and stirred at room temperature for 1.5 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 2.20 g of N-[2-(3,4-dimethoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide.

[0211] 1 H-NMR(CDCl3, TMS) δ(ppm): 13.61(1H,d,J=11.2Hz), 6.9-7.1(2H,m), 6.6-6.8(5H, m), 5.56(1H,br), 3.86(3H,s), 3.82(3H,s), 3.4-3.6(2H,m), 2.6-2.9(6H,m), 1.7-1.9(4H,m)

Reference Production Example 4

[0212] 15.2 g (0.1 mol) of vanilline, 20.5 g (0.12 mol) of benzyl bromide, 17.9 g (0.13 mol) of potassium carbonate and 150 ml of N,N-dimethylformamide were mixed and stirred at 50° C. for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochloric acid and then saturated brine, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 23.1 g of 4-benzyloxy-3-methoxybenzaldehyde.

[0213] 1 H-NMR(CDCl3, TMS) δ(ppm): 9.83(1H,s), 7.5-7.3(7H,m), 6.98(1H,d, J=8.2Hz), 5.24(2H,s), 3.95(3H,s)

[0214] 23.1 g (95.7 mmol) of 4-benzyloxy-3-methoxybenzaldehyde, 8.76 g (143 mmol) of nitromethane and 250 ml of acetic acid were mixed and 7.07 g (96.7 mmol) of butylamine was added dropwise thereto. The mixture was refluxed for 2 hours by heating, and then cooled and poured into ice-water. The precipitated crystals were dissolved with ethyl acetate, washed with saturated brine, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 17.0 g of 1-benzyloxy-2-methoxy-4-(2-nitrovinyl)benzene.

[0215] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.95(1H,d,J=13.5Hz), 7.51(1H,d,J=14.7Hz), 7.3-7.5(5H,m), 5.24(2H,s), 3.95(3H,s)

[0216] 6.78 g (178.8 mmol) of lithium aluminum hydride and 200 ml of anhydrous tetrahydrofuran were mixed and an anhydrous tetrahydrofuran solution of 17.0 g (59.6 mmol) of 1-benzyloxy-2-methoxy-4-(2-nitrovinyl)benzene was added dropwise thereto over about 90 minutes under vigorous stirring. The mixture was refluxed for 2 hours by heating, and then cooled and aqueous sodium hydroxide solution was added to the mixture. The precipitates were filtered off with celite-precoated glass filter and the solvent was distilled off from the filtrate under reduced pressure. The residue was extracted with ethyl acetate, washed with saturated brine, dried over potassium carbonate and the solvent was distilled off under reduced pressure to give 13.67 g of crude 2-(3-methoxy-4-benzyloxyphenyl) ethylamine.

[0217] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.5(5H,m), 6.6-6.9(3H,m), 5.10(2H,s), 3.85(3H,s), 2.90(2H,t,J=6.7Hz), 2.66(2H,t,J=6.8Hz), 2.0-2.4(2H,br)

[0218] 8.01 g (31.2 mmol) of crude 2-(3-methoxy-4-benzyloxyphenyl)ethylamine, 3.78 g (37.4 mmol) of triethylamine and 80 ml of tetrahydrofuran were mixed and cooled to 0° C. and then (5,6,7,8-tetrahydronaphthalen-2-yl)acetyl chloride was added dropwise thereto. The mixture was stirred at 0° C. for 30 minutes and further at room temperature for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochloric acid and then saturated brine, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =1:1) to give 8.3 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2 -yl)acetamide.

[0219] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.2(4H,m), 6.72(1H,d,J=8.2Hz), 6.5-6.6(2H,m), 5.4(1H,s), 3.86(3H,s), 3.82(3H,s), 3.49(2H,s), 3.3-3.4(2H,m), 2.67(2H,t,J=6.9Hz), 2.34(3H,s)

[0220] 8.8 g (13.6 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acetamide, 8.9 g (51.1 mmol) of t-butoxybis (dimethylamino)methane and 100 ml of N,N-dimethylformamide were mixed and stirred at 100° C. for 6 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. To the residue, 50 ml of 5% hydrochloric acid and 100 ml of tetrahydrofuran were added and stirred at room temperature for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =2:1) and dried to give 4.20 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide.

[0221] 1 H-NMR(CDCl3, TMS) δ(ppm): 13.61(1H,d,J=11.3Hz), 7.2-7.5(5H,m), 7.04(1H,d, J=11.0Hz), 6.97(1H,d,J=8.2Hz), 6.7-6.9(3H,m), 6.66(1H,d,J=2.0Hz), 6.59(1H,dd,J=8.3, 1.9Hz), 5.55(1H,br), 5.11(2H,s), 3.83(3H,s), 3.4-3.6(2H,m), 2.6-2.9(6H,m), 1.7-1.9(4H,m)

Reference Production Example 5

[0222] 15 .26 g (59.3 mmol) of crude 2-(3-methoxy-4-benzyloxyphenyl)ethylamine, 9.09 g (89.0 mmol) of triethylamine and 100 ml of tetrahydrofuran were mixed and cooled to about 0° C. and then 5.44 g (32.28 mmol) of (4-methylphenyl)acetyl chloride was added dropwise thereto. The mixture was stirred at 0° C. for 30 minutes and further at room temperature for 3 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochloric acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 19.48 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl)acetamide.

[0223] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.5(5H,m), 7.0-7.1(4H,m), 6.73(1H,d, J=8.2Hz), 6.62(1H,d,J=1.9Hz), 6.46(1H,dd,J=8.1,1.9Hz), 5.34(1H,br), 5.12(2H,s), 3.83(3H,s), 3.4-3.5(4H,m), 2.64(2H,t,J=6.9Hz), 2.32(3H,s)

[0224] 11.68 g (30.0 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-methylphenyl) acetamide and 15.67 g (90.0 mmol) of t-butoxybis(dimethylamino) methane were mixed and stirred at 80° C. for 2 hours. The reaction mixture was cooled and tetrahydrofuran was added thereto. The reaction mixture was acidified with 5% hydrochloric acid and stirred at room temperature for 2 hours. After the solvent was distilled off under reduced pressure, water and 5% hydrochloric acid were added to the residue, which was followed by extracted with chloroform twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 11.30 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide.

[0225] 1 H-NMR(CDCl3, TMS) δ(ppm): 13.61(1H,d,J=11.3Hz), 7.2-7.5(5H,m), 6.9-7.1(5H,m), 6.77(1H,d,J=8.1Hz), 6.64(1H,d,J=1.6Hz), 6.56(1H,dd,J=8.1,1.6Hz), 5.46(1H,br), 5.13(2H,s), 3.83(3H,s), 3.4-3.6(2H,m), 2.73(2H,t,J=6.8Hz), 2.33(3H,s)

Reference Production Example 6

[0226] 2.14 g (11.97 mmol) of crude 2-(3-methoxy-4-benzyloxyphenyl)ethylamine, 1.45 g (14.36 mmol) of triethylamine and 20 ml of tetrahydrofuran were mixed and cooled to about 0° C. and then 2.26 g (11.97 mmol) of (4-chlorophenyl)acetyl chloride was added dropwise thereto. The mixture was stirred at 0° C. for 30 minutes and further at room temperature for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochloric acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 3.70 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl)acetamide.

[0227] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.5(7H,m), 7.0-7.1(2H,m), 6.73(1H,d, J=8.3Hz), 6.63(1H,d,J=2.0Hz), 6.43(1H,dd,J=8.0,2.0Hz), 5.29(1H,br), 5.14(2H,s), 3.84(3H,s), 3.4-3.5(4H,m), 2.66(2H,t,J=6.8Hz)

[0228] 2.25 g (5.49 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-2-(4-chlorophenyl) acetamide and 2.39 g (13.73 mmol) of t-butoxybis(dimethylamino) methane were mixed and stirred at 90° C. for 1.5 hours. The reaction mixture was cooled and tetrahydrofuran was added thereto. The reaction mixture was acidified with 5% hydrochloric acid and stirred at room temperature for 2 hours. After the solvent was distilled off under reduced pressure, water and 5% hydrochloric acid were added to the residue, which was followed by extracted with ethyl acetate, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 1.50 g of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide.

[0229] 1 H-NMR(CDCl3, TMS) δ(ppm): 13.67(1H,d,J=11.0Hz), 7.2-7.5(7H,m), 6.9-7.1(3H,m), 6.76(1H,d,J=8.3Hz), 6.65(1H,d,J=1.8Hz), 6.52(1H,dd,J=8.0,2.0Hz), 5.32(1H,br), 5.15(2H,s), 3.84(3H,s), 3.4-3.6(2H,m), 2.73(2H,t,J=6.8Hz)

Reference Production Example 7

[0230] Two grams (2.00 g) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide (4.79 mmol), 1.21 g (7.19 mmol) of 48% hydrobromic acid and 20 ml of acetic acid were mixed and stirred at 80° C. for 1.5 hours. The solvent was distilled off from the reaction mixture under reduced pressure and the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 630 mg of 3-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]-2-(4-methylphenyl)acrylamide.

[0231] 1 H-NMR(CDCl3, TMS) δ(ppm): 13.6(1H,d,J=11.3Hz), 6.9-7.2(5H,m), 6.80(1H,d, J=7.8Hz), 6.5-6.6(2H,m), 5.4-5.5(2H,m), 3.83(3H,s), 3.4-3.6(2H,m), 2.74(2H,t,J=6.9Hz), 2.35(3H,s)

Reference Production Example 8

[0232] 1.60 g (3.66 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)ethyl]-3-hydroxy-2-(4-chlorophenyl)acrylamide, 925 mg (5.49 mmol) of 48% hydrobromic acid and 15 ml of acetic acid were mixed and stirred at 80° C. for 1.5 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate twice, washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 600 mg of 2-(4-chlorophenyl)-3-hydroxy-N-[2-(4-hydroxy-3-methoxyphenyl) ethyl]acrylamide.

[0233] 1 H-NMR(CDCl3, TMS) δ(ppm): 13.6(1H,d,J=11.3Hz), 7.2-7.4(2H,m), 7.0-7.1(3H, m), 6.82(1H,d,J=6.7,1.7Hz), 6.5-6.6(2H,m), 5.54(1H,s), 5.32(1H,br), 3.83(3H,s), 3.4-3.6 (2H,m), 2.74(2H,t,J=6.9Hz)

Reference Production Example 9

[0234] 4.02 g (55.0 mmol) of butylamine was added dropwise to a mixture of 12.1 g (50.0 mmol) of 4-benzyloxy-3-methoxybenzaldehyde, 5.63 g (75.0 mmol) of nitroethane and 120 ml of acetic acid and refluxed for 5 hours by heating. The reaction mixture was cooled and extracted with ethyl acetate, washed with saturated brine, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =4:1) to give 2.70 g of 1-benzyloxy-2-methoxy-4-(2-nitropropenyl)benzene.

[0235] 1 H-NMR(CDCl3, TMS) δ(ppm): 8.04(1H,s), 7.3-7.5(5H,m), 6.9-7.1(3H,m), 5.21(2H,s), 3.92(3H,s), 2.47(3H,s)

[0236] To a mixture of 1.03 g (27.1 mmol) of lithium aluminum hydride and 20 ml of anhydrous tetrahydrofuran, an anhydrous tetrahydrofuran solution of 2.70 g (9.03 mmol) of 1-benzyloxy-2-methoxy-4-(2-nitropropenyl)benzene was added dropwise under vigorous stirring over about 90 minutes and refluxed for 2 hours by heating. The reaction mixture was cooled and aqueous sodium hydroxide solution was added thereto. After the precipitates were filtered off with celite-precoated glass filter, the solvent was distilled off from the filtrate under reduced pressure. The residue was extracted with ethyl acetate, washed with saturated brine, dried over potassium carbonate and the solvent was distilled off under reduced pressure to give 2.30 g of crude 2-(4-benzyloxy-3-methoxyphenyl)-1-methylethylamine.

[0237] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.5(5H,m), 6.6-6.9(3H,m), 5.12(2H,s), 3.87 (3H,s), 3.1-3.2(1H,m), 2.4-2.8(2H,m), 1.4-2.0(2H,br), 1.11(3H,d,J=6.3Hz)

[0238] 2.30 g (8.48 mmol) of crude 2-(4-benzyloxy-3-methoxyphenyl)-1-methylethylamine, 1.03 g (10.2 mmol) of triethylamine and 25 ml of tetrahydrofuran were mixed and cooled to about 0° C. and then 1.42 g (8.48 mmol) of (4-methylphenyl)acetyl chloride was added dropwise thereto. The mixture was stirred at 0° C. for 30 minutes and further at room temperature for 2 hours. Water was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochloric acid and saturated brine subsequently, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was washed with hexane and dried to give 2.40 g of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-2-(4-methylphenyl) acetamide.

[0239] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.3-7.5(5H,m), 6.9-7.1(4H,m), 6.72(1H,d,J=8.1Hz), 6.62(1H,d,J=1.9Hz), 6.42(1H,dd,J=2.0,8.1Hz), 5.1-5.3(2H,m), 4.1-4.3(1H,m), 3.83(3H,s), 3.45(2H,s), 2.59(2H,d,J=6.4Hz), 2.33(3H,s), 1.04(3H,d,J=6.6Hz)

[0240] 2.40 g (5.95 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-2-(4-methylphenyl)acetamide and 3.10 g (17.8 mmol) of t-butoxybis(dimethylamino) methane were mixed and stirred at 80° C. for 2 hours. The reaction mixture was cooled and tetrahydrofuran was added thereto. The reaction mixture was acidified with hydrochloric acid and stirred at room temperature for 2 hours. After the solvent was distilled off under reduced pressure, the residue was extracted with chloroform washed with saturated brine twice, dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate =3:2) and dried to give 1.90 g of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide.

[0241] 1 H-NMR(CDCl3, TMS) δ(ppm): 13.65(1H,d,J=11.2Hz), 7.2-7.5(5H,m), 6.9-7.2(5H, m), 6.76(1H,d,J=8.2Hz), 6.63(1H,d,J=1.88Hz), 6.52(1H,dd,J=8.1,1.9Hz), 5.28(2H,d, J=7.6Hz), 5.14(2H,s), 4.2-4.4(1H,d), 3.83(3H,s), 3.6-3.8(2H,m), 2.35(3H,s), 1.11(3H,d, J=6.5Hz)

[0242] 1.90 g (4.41 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-hydroxy-2-(4-methylphenyl)acrylamide, 0.99 g (17.6 mmol) of 10% aqueous potassium hydroxide solution, 716 mg (2.20 mmol) of tetrabutylammonium bromide and 20 ml of ethylene glycol dimethyl ether were mixed and chlorodifluoromethane gas was blown thereto at room temperature to 50° C. After a sample was taken out from the reaction mixture and the disappearance of the starting material was confirmed by thin layer chromatograph analysis, the reaction mixture was cooled. Then, 5% hydrochrolic acid was added to the reaction mixture, which was followed by extracted with ethyl acetate, washed with 5% hydrochrolic acid, saturated brine subsequently, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was washed with hexane to give 1.80 g of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-difluoromethoxy-2-(4-methylphenyl) acrylamide.

[0243] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.2-7.5(5H,m), 7.0-7.2(4H,m), 6.7-6.9(4H,m), 6.63 (1H,dd,J=8.0,1.8Hz), 6.30(1H,t,J=71.7Hz), 5.79(1H,d,J=8.1Hz), 5.13(2H,s), 4.3-4.6(1H,m), 3.83(3H,s), 2.6-2.9(2H,m), 2.33(3H,s), 1.18(3H,d,J=6.6Hz)

[0244] 1.80 g (3.74 mmol) of N-[2-(4-benzyloxy-3-methoxyphenyl)-1-methylethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide, 693 mg (4.11 mmol) of 48% hydrobromic acid and 20 ml of acetic acid were mixed and stirred at 80° C. for 2 hours. The solvent was distilled off from the reaction mixture under reduced pressure and the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate =2:1) to give 1.10 g of 3-difluoromethoxy-N-[2-(4-hydroxy-3-methoxyphenyl)-1-methylethyl]-2-(4-methylphenyl)acrylamide.

[0245] 1 H-NMR(CDCl3, TMS) δ(ppm): 7.1-7.2(4H,m), 6.6-6.9(4H,m), 6.37(1H,t, J=71.5Hz), 5.79(1H,d,J=7.7Hz), 5.58(1H,s), 4.3-4.5(1H,m), 3.82(3H,s), 2.6-2.9(2H,m), 2.34(3H,s), 1.18(3H,d,J=6.5Hz)

[0246] Examples of the present compounds are given with their compound numbers below.

[0247] Compound given by formula [I]:

9
Nos.	R1X	Ar	Y	R2	A	Z1	Z2
1001	CH2FO	C6H5	O	H	CH2CH2	CH3O	CH3O
1002	CHF2O	C6H5	O	H	CH2CH2	CH3O	CH3O
1003	CF3O	C6H5	O	H	CH2CH2	CH3O	CH3O
1004	CH2FO	4-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1005	CHF2O	4-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1006	CF3O	4-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1007	CH2FO	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH3O
1008	CHF2O	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH3O
1009	CF3O	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH3O
1010	CH2FO	4-CH3CH2CH2C6H4	O	H	CH2CH2	CH3O	CH3O
1011	CHF2O	4-CH3CH2CH2C6H4	O	H	CH2CH2	CH3O	CH3O
1012	CF3O	4-CH3CH2CH2C6H4	O	H	CH2CH2	CH3O	CH3O
1013	CH2FO	4-FC6H4	O	H	CH2CH2	CH3O	CH3O
1014	CHF2O	4-FC6H4	O	H	CH2CH2	CH3O	CH3O
1015	CF3O	4-FC6H4	O	H	CH2CH2	CH3O	CH3O
1016	CH2FO	4-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1017	CHF2O	4-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1018	CF3O	4-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1019	CH2PO	4-BrC6H4	O	H	CH2CH2	CH3O	CH3O
1020	CHF2O	4-BrC6H4	O	H	CH2CH2	CH3O	CH3O
1021	CF3O	4-BrC6H4	O	H	CH2CH2	CH3O	CH3O
1022	CH2FO	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH3O
1023	CHF2O	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH3O
1024	CF3O	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH3O
1025	CH2PO	4-CH3SC6H4	O	H	CH2CH2	CH3O	CH3O
1026	CHF2O	4-CH3SC6H4	O	H	CH2CH2	CH3O	CH3O
1027	CF3O	4-CH3SC6H4	O	H	CH2CH2	CH3O	CH3O
1028	CH2FO	4-CF3C6H4	O	H	CH2CH2	CH3O	CH3O
1029	CHF2O	4-CF3C6H4	O	H	CH2CH2	CH3O	CH3O
1030	CF3O	4-CF3C6H4	O	H	CH2CH2	CH3O	CH3O
1031	CH2FO	4-(CH3)3CC6H4	O	H	CH2CH2	CH3O	CH3O
1032	CHF2O	4-(CH3)3CC6H4	O	H	CH2CH2	CH3O	CH3O
1033	CF3O	4-(CH3)3CC6H4	O	H	CH2CH2	CH3O	CH3O
1034	CH2FO	3-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1035	CHF2O	3-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1036	CF3O	3-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1037	CH2FO	3-C2H5C6H4	O	H	CH2CH2	CH3O	CH3O
1038	CHF2O	3-C2H5C6H4	O	H	CH2CH2	CH3O	CH3O
1039	CF3O	3-C2H5C6H4	O	H	CH2CH2	CH3O	CH3O
1040	CH2FO	3-CH3CH2CH2C6H4	O	H	CH2CH2	CH3O	CH3O
1041	CHF2O	3-CH3CH2CH2C6H4	O	H	CH2CH2	CH3O	CH3O
1042	CF3O	3-CH3CH2CH2C6H4	O	H	CH2CH2	CH3O	CH3O
1043	CH2FO	3-FC6H4	O	H	CH2CH2	CH3O	CH3Q
1044	CHF2O	3-FC6H4	O	H	CH2CH2	CH3O	CH3O
1045	CF3O	3-FC6H4	O	H	CH2CH2	CH3Q	CH3O
1046	CH2FO	3-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1047	CHF2O	3-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1048	CF3O	3-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1049	CH2FO	3-BrC6H4	O	H	CH2CH2	CH3O	CH3O
1050	CHF2O	3-BrC6H4	O	H	CH2CH2	CH3O	CH3O
1051	CF3O	3-BrC6H4	O	H	CH2CH2	CH3O	CH3O
1052	CH2FO	3-CH3OC6H4	O	H	CH2CH2	CH3O	CH3O
1053	CHF2O	3-CH3OC6H4	O	H	CH2CH2	CH3O	CH3O
1054	CF3O	3-CH3OC6H4	O	H	CH2CH2	CH3O	CH3O
1055	CH2FO	3-CH3SC6H4	O	H	CH2CH2	CH3O	CH3O
1056	CHF2O	3-CH3SC6H4	O	H	CH2CH2	CH3O	CH3O
1057	CF3O	3-CH3SC6H4	O	H	CH2CH2	CH3O	CH3O
1058	CH2FO	3-CF3C6H4	O	H	CH2CH2	CH3O	CH3O
1059	CHF2O	3-CF3C6H4	O	H	CH2CH2	CH3O	CH3O
1060	CF3O	3-CF3C6H4	O	H	CH2CH2	CH3O	CH3O
1061	CH2FO	3,4-F2C6H3	O	H	CH2CH2	CH3O	CH3O
1062	CHF2O	3,4-F2C6H3	O	H	CH2CH2	CH3O	CH3O
1063	CF3O	3,4-F2C6H3	O	H	CH2CH2	CH3O	CH3O
1064	CH2FO	3,4-Cl2C6H3	O	H	CH2CH2	CH3O	CH3O
1065	CHF2O	3,4-Cl2C6H3	O	H	CH2CH2	CH3O	CH3O
1066	CF3O	3,4-Cl2C6H3	O	H	CH2CH2	CH3O	CH3O
1067	CH2FO	3,4-Br2C6H3	O	H	CH2CH2	CH3O	CH3O
1068	CHF2O	3,4-Br2C6H3	O	H	CH2CH2	CH3O	CH3O
1069	CF3O	3,4-Br2C6H3	O	H	CH2CH2	CH3O	CH3O
1070	CH2FO	3,4-(CH3)2C6H3	O	H	CH2CH2	CH3O	CH3O
1071	CHF2O	3,4-(CH3)2C6H3	O	H	CH2CH2	CH3O	CH3O
1072	CF3O	3,4-(CH3)2C6H3	O	H	CH2CH2	CH3O	CH3O
1073	CH2FO	3,4-(CH3O)2C6H3	O	H	CH2CH2	CH3O	CH3O
1074	CHF2O	3,4-(CH3O)2C6H3	O	H	CH2CH2	CH3O	CH3O
1075	CF3O	3,4-(CH3O)2C6H3	O	H	CH2CH2	CH3O	CH3O
1076	CH2FO	3,4-(CF3)2C6H3	O	H	CH2CH2	CH3O	CH3O
1077	CHF2O	3,4-(CF3)2C6H3	O	H	CH2CH2	CH3O	CH3O
1078	CF3O	3,4-(CF3)2C6H3	O	H	CH2CH2	CH3O	CH3O
1079	CH2FO	4-Cl-3-CH3C6H3	O	H	CH2CH2	CH3O	CH3O
1080	CHF2O	4-Cl-3-CH3C6H3	O	H	CH2CH2	CH3O	CH3O
1081	CF3O	4-Cl-3-CH3C6H3	O	H	CH2CH2	CH3O	CH3O
1082	CH2FO	3-Cl-4-CH3C6H3	O	H	CH2CH2	CH3O	CH3O
1083	CHF2O	3-Cl-4-CH3C6H3	O	H	CH2CH2	CH3O	CH3O
1084	CF3O	3-Cl-4-CH3C6H3	O	H	CH2CH2	CH3O	CH3O
1085	CH2FO	4-Cl-3-CH3OC6H3	O	H	CH2CH2	CH3O	CH3O
1086	CHF2O	4-Cl-3-CH3OC6H3	O	H	CH2CH2	CH3O	CH3O
1087	CF3O	4-Cl-3-CH3OC6H3	O	H	CH2CH2	CH3O	CH3O
1088	CH2FO	3-Cl-4-CH3OC6H3	O	H	CH2CH2	CH3O	CH3O
1089	CHF2O	3-Cl-4-CH3OC6H3	O	H	CH2CH2	CH3O	CH3O
1090	CF3O	3-Cl-4-CH3OC6H3	O	H	CH2CH2	CH3O	CH3O
1091	CH2FO	3,4-(OCH2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1092	CHF2O	3,4-(OCH2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1093	CF3O	3,4-(OCH2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1094	CH2FO	3,4-(OCH2CH2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1095	CHF2O	3,4-(OCH2CH2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1096	CF3O	3,4-(OCH2CH2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1097	CH2FO	3,4-(OCF2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1098	CHF2O	3,4-(OCF2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1099	CF3O	3,4-(OCF2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1100	CH2FO	3,4-(CH2)33C6H3	O	H	CH2CH2	CH3O	CH3O
1101	CHF2O	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	CH3O
1102	CF3O	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	CH3O
1103	CH2FO	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3O
1104	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3O
1105	CF3O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3O
1106	CH2FO	3,4-(CH2)5C6H3	O	H	CH2CH2	CH3O	CH3O
1107	CHF2O	3,4-(CH2)5C6H3	O	H	CH2CH2	CH3O	CH3O
1108	CF3O	3,4-(CH2)5C6H3	O	H	CH2CH2	CH3O	CH3O
1109	CH2FO	C6H5	O	CH3	CH(CH3)CH2	CH3O	CH3O
1110	CHF2O	C6H5	O	CH3	CH(CH3)CH2	CH3O	CH3O
1111	CF3O	C6H5	O	CH3	CH(CH3)CH2	CH3O	CH3O
1112	CH2FO	4-CH3C6H4	O	CH3	CH(CH3)CH2	CH3O	CH3O
1113	CHF2O	4-CH3C6H4	O	CH3	CH(CH3)CH2	CH3O	CH3O
1114	CF3O	4-CH3C6H4	O	CH3	CH(CH3)CH2	CH3O	CH3O
1115	CH2FO	4-ClC6H4	O	CH3	CH(CH3)CH2	CH3O	CH3O
1116	CHF2O	4-ClC6H4	O	CH3	CH(CH3)CH2	CH3O	CH3O
1117	CF3O	4-ClC6H4	O	CH3	CH(CH3)CH2	CH3O	CH3O
1118	CH2FO	3,4-(OCF2O)C6H3	O	CH3	CH(CH3)CH2	CH3O	CH3O
1119	CHF2O	3,4-(OCF2O)C6H3	O	CH3	CH(CH3)CH2	CH3O	CH3O
1120	CF3O	3,4-(OCF2O)C6H3	O	CH3	CH(CH3)CH2	CH3O	CH3O
1121	CH2FO	3,4-(CH2)3C6H3	O	CH3	CH(CH3)CH2	CH3O	CH3O
1122	CHF2O	3,4-(CH2)3C6H3	O	CH3	CH(CH3)CH2	CH3O	CH3O
1123	CF3O	3,4-(CH2)3C6H3	O	CH3	CH(CH3)CH2	CH3O	CH3O
1124	CH2FO	3,4-(CH2)4C6H3	O	CH3	CH(CH3)CH2	CH3O	CH3O
1125	CHF2O	3,4-(CH2)4C6H3	O	CH3	CH(CH3)CH2	CH3O	CH3O
1126	CF3O	3,4-(CH2)4C6H3	O	H	CH(CH3)CH2	CH3O	CH3O
1127	CH2FO	C6H5	O	H	CH2CH2	CH3O	C2H5O
1128	CHF2O	C6H5	O	H	CH2CH2	CH3O	C2H5O
1129	CF3O	C6H5	O	H	CH2CH2	CH3O	C2H5O
1130	CH2FO	4-CH3C6H4	O	H	CH2CH2	CH3O	C2H5O
1131	CHF2O	4-CH3C6H4	O	H	CH2CH2	CH3O	C2H5O
1132	CF3O	4-CH3C6H4	O	H	CH2CH2	CH3O	C2H5O
1133	CH2FO	4-ClC6H4	O	H	CH2CH2	CH3O	C2H5O
1134	CHF2O	4-ClC6H4	O	H	CH2CH2	CH3O	C2H5O
1135	CF3O	4-ClC6H4	O	H	CH2CH2	CH3O	C2H5O
1136	CH2FO	3,4-(OCF2O)C6H3	O	H	CH2CH2	CH3O	C2H5O
1137	CHF2O	3,4-(OCF2O)C6H3	O	H	CH2CH2	CH3O	C2H5O
1138	CF3O	3,4-(OCF2O)C6H3	O	H	CH2CH2	CH3O	C2H5O
1139	CH2FO	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	C2H5O
1140	CHF2O	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	C2H5O
1141	CF3O	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	C2H5O
1142	CH2FO	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	C2H5O
1143	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	C2H5O
1144	CF3O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	C2H5O
1145	CH2FO	C6H5	S	H	CH2CH2	CH3O	CH3O
1146	CHF2O	C6H5	S	H	CH2CH2	CH3O	CH3O
1147	CF3O	C6H5	S	H	CH2CH2	CH3O	CH3O
1148	CH2FO	4-CH3C6H4	S	H	CH2CH2	CH3O	CH3O
1149	CHF2O	4-CH3C6H4	S	H	CH2CH2	CH3O	CH3O
1150	CF3O	4-CH3C6H4	S	H	CH2CH2	CH3O	CH3O
1151	CH2FO	4-ClC6H4	S	H	CH2CH2	CH3O	CH3O
1152	CHF2O	4-ClC6H4	S	H	CH2CH2	CH3O	CH3O
1153	CF3O	4-ClC6H4	S	H	CH2CH2	CH3O	CH3O
1154	CH2FO	3,4-(OCF2O)C6H3	S	H	CH2CH2	CH3O	CH3O
1155	CHF2O	3,4-(OCF2O)C6H3	S	H	CH2CH2	CH3O	CH3O
1156	CF3O	3,4-(OCF2O)C6H3	S	H	CH2CH2	CH3O	CH3O
1157	CH2FO	3,4-(CH2)3C6H3	S	H	CH2CH2	CH3O	CH3O
1158	CHF2O	3,4-(CH2)3C6H3	S	H	CH2CH2	CH3O	CH3O
1159	CF3O	3,4-(CH2)3C6H3	S	H	CH2CH2	CH3O	CH3O
1160	CH2FO	3,4-(CH2)4C6H3	S	H	CH2CH2	CH3O	CH3O
1161	CHF2O	3,4-(CH2)4C6H3	S	H	CH2CH2	CH3O	CH3O
1162	CF3O	3,4-(CH2)4C6H3	S	H	CH2CH2	CH3O	CH3O
1163	CH2FS	C6H5	O	H	CH2CH2	CH3O	CH3O
1164	CHF2S	C6H5	O	H	CH2CH2	CH3O	CH3O
1165	CF3S	C6H5	O	H	CH2CH2	CH3O	CH3O
1166	CH2FS	4-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1167	CHF2S	4-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1168	CF3S	4-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1169	CH2FS	4-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1170	CHF2S	4-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1171	CF3S	4-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1172	CH2FS	3,4-(OCF2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1173	CHF2S	3,4-(OCF2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1174	CF3S	3,4-(OCF2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1175	CH2FS	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	CH3O
1176	CHF2S	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	CH3O
1177	CF3S	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	CH3O
1178	CH2FS	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3O
1179	CHF2S	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3O
1180	CF3S	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3O
1181	CH≡CCH2O	C6H5	O	H	CH2CH2	CH3O	CH3O
1182	CH≡CCH2O	4-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1183	CH≡CCH2O	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH3O
1184	CH≡CCH2O	4-FC6H4	O	H	CH2CH2	CH3O	CH3O
1185	CH≡CCH2O	4-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1186	CH≡CCH2O	4-BrC6H4	O	H	CH2CH2	CH3O	CH3O
1187	CH≡CCH2O	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH3O
1188	CH≡CCH2O	4-CF3C6H4	O	H	CH2CH2	CH3O	CH3O
1189	CH≡CCH2O	4-(CH3)3CC6H4	O	H	CH2CH2	CH3O	CH3O
1190	CH≡CCH2O	3,4-Cl2C6H3	O	H	CH2CH2	CH3O	CH3O
1191	CH≡CCH2O	3,4-(CH3)2C6H3	O	H	CH2CH2	CH3O	CH3O
1192	CH≡CCH2O	3,4-(OCH2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1193	CH≡CCH2O	3,4-(OCH2CH2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1194	CH≡CCH2O	3,4-(OCF2O)C6H3	O	H	CH2CH2	CH3O	CH3O
1195	CH≡CCH2O	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	CH3O
1196	CH≡CCH2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3O
1197	CHBrF2O	4-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1198	CHBrF2O	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH3O
1199	CHBrF2O	4-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1200	CHBrF2O	4-BrC6H4	O	H	CH2CH2	CH3O	CH3O
1201	CHBrF2O	4-CF3C6H4	O	H	CH2CH2	CH3O	CH3O
1202	CHBrF2O	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH3O
1203	CHBrF2O	4-CF3OC6H4	O	H	CH2CH2	CH3O	CH3O
1204	CHBrF2O	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	CH3O
1205	CHBrF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3O
1206	CHClF2O	4-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1207	CHClF2O	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH3O
1208	CHClF2O	4-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1209	CHClF2O	4-BrC6H4	O	H	CH2CH2	CH3O	CH3O
1210	CHClF2O	4-CF3C6H4	O	H	CH2CH2	CH3O	CH3O
1211	CHClF2O	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH3O
1212	CHClF2O	4-CF3OC6H4	O	H	CH2CH2	CH3O	CH3O
1213	CHClF2O	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	CH3O
1214	CHClF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3O
1215	CCl≡CCH2O	4-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1216	CCl≡CCH2O	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH3O
1217	CCl≡CCH2O	4-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1218	CCl≡CCH2O	4-BrC6H4	O	H	CH2CH2	CH3O	CH3O
1219	CCl≡CCH2O	4-CF3C6H4	O	H	CH2CH2	CH3O	CH3O
1220	CCl≡CCH2O	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH3O
1221	CCl≡CCH2O	4-CF3OC6H4	O	H	CH2CH2	CH3O	CH3O
1222	CCl≡CCH2O	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	CH3O
1223	CCl≡CCH2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3O
1224	CCl2═CHCH2O	4-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1225	CCl2═CHCH2O	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH3O
1226	CCl2═CHCH2O	4-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1227	CCl2═CHCH2O	4-BrC6H4	O	H	CH2CH2	CH3O	CH3O
1228	CCl2═CHCH2O	4-CF3C6H4	O	H	CH2CH2	CH3O	CH3O
1229	CCl2═CHCH2O	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH3O
1230	CCl2═CHCH2O	4-CF3OC6H4	O	H	CH2CH2	CH3O	CH3O
1231	CCl2═CHCH2O	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	CH3O
1232	CCl2═CHCH2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3O
1233	CH2FCH2O	4-CH3C6H4	O	H	CH2CH2	CH3O	CH3O
1234	CH2FCH2O	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH3O
1235	CH2FCH2O	4-ClC6H4	O	H	CH2CH2	CH3O	CH3O
1236	CH2FCH2O	4-BrC6H4	O	H	CH2CH2	CH3O	CH3O
1237	CH2FCH2O	4-CF3C6H4	O	H	CH2CH2	CH3O	CH3O
1238	CH2FCH2O	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH3O
1239	CH2FCH2O	4-CF3OC6H4	O	H	CH2CH2	CH3O CH3O
1240	CH2FCH2O	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O CH3O
1241	CH2FCH2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O CH3O
1242	CClF2O	2-naphthyl	O	H	CH2CH2	CH3O CH3O
1243	CBrF2O	2-naphthyl	O	H	CH2CH2	CH3O CH3O
1244	CH2FCH2O	2-naphthyl	O	H	CH2CH2	CH3O CH3O
1245	CH≡CCH2O	2-naphthyl	O	H	CH2CH2	CH3O CH3O
1246	CH2FO	4-NO2C6H4	O	H	CH2CH2	CH3O CH3O
1247	CHF2O	4-NO2C6H4	O	H	CH2CH2	CH3O CH3O
1248	CF3O	4-NO2C6H4	O	H	CH2CH2	CH3O CH3O
1249	CH═CCH2O	4-NO2C6H4	O	H	CH2CH2	CH3O CH3O
1250	CH2FO	4-(CH3)2CHC6H4	O	H	CH2CH2	CH3O CH3O
1251	CHF2O	4-(CH3)2CHC6H4	O	H	CH2CH2	CH3O CH3O
1252	CF3O	4-(CH3)2CHC6H4	O	H	CH2CH2	CH3O CH3O
1253	CH≡CCH2O	4-(CH3)2CHC6H4	O	H	CH2CH2	CH3O CH3O
1254	CH2FO	4-cyclopropylphenyl	O	H	CH2CH2	CH3O CH3O
1255	CHF2O	4-cyclopropylphenyl	O	H	CH2CH2	CH3O CH3O
1256	CF3O	4-cyclopropylphenyl	O	H	CH2CH2	CH3O CH3O
1257	CH≡CCH2O	4-cyclopropylphenyl	O	H	CH2CH2	CH3O CH3O
1258	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3CH2CH2O
1259	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	(CH3)2CHO
1260	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	cyclopropoxy
1261	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	Cyclopropyl-
							methoxy
1262	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	butoxy
1263	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	isobutoxy
1264	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	sec-butoxy
1265	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	t-butoxy
1266	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	allyloxy
1267	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	2-butenyloxy
1268	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1269	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	2-butynyloxy
1270	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	2-pentynyl-
							oxy
1271	CHF2O	4-CH3C6H4	O	H	CH2CH2	CH3O	1-methyl-2-
							propynyloxy
1272	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	3-butynyloxy
1273	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	4-pentynyl-
							oxy
1274	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	NCCH2O
1275	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3S
1276	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	C2H5S
1277	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH2FO
1278	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CHF2O
1279	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CF3O
1280	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CF3CH2O
1281	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	C6H4CH2O
1282	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3CO2
1283	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	C2H5CO2
1284	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O CH3OCH2O
1285	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	ethoxy-
							methoxy
1286	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH3NHCO2
1287	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	3,3-dichloro-
							allyloxy
1288	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	3-chloro-2-
							propynyl
1289	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3CH2CH2O	CH3O
1290	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	(CH3)2CHO	CH3O
1291	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	cyclopropoxy	CH3O
1292	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	Cyclopropyl-	CH3O
						methoxy
1293	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	butoxy	CH3O
1294	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	isobutoxy	CH3O
1295	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	sec-butoxy	CH3O
1296	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	t-butoxy	CH3O
1297	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	allyloxy	CH3O
1298	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	2-butenyl-	CH3O
						oxy
1299	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH≡CCH2O	CH3O
1300	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	2-butynyl-	CH3O
						oxy
1301	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	2-pentynyl	CH3O
						oxy
1302	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	1-methyl-2-	CH3O
						propynyloxy
1303	CHF2O	3,4(CH2)4C6H3	O	H	CH2CH2	3-butynyl	CH3O
						oxy
1304	CHF2O	3,4(CH2)4C6H3	O	H	CH2CH2	4-pentynyl	CH3O
						oxy
1305	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	NCCH2O	CH3O
1306	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3S	CH3O
1307	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5S	CH3O
1308	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH2FO	CH3O
1309	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CHF2O	CH3O
1310	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CF3O	CH3O
1311	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CF3CH2O	CH3O
1312	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	OH	CH3O
1313	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3CO2	CH3O
1314	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5CO2	CH3O
1315	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3OCH2O	CH3O
1316	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	ethoxy-	CH3O
						methoxy
1317	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3NHCO2	CH3O
1318	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	3,3-dichloro-	CH3O
						allyloxy
1319	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	3-chloro-2-	CH3O
						propynyl
1320	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5O	CH3O
1321	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5O	C2H5O
1322	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5O	CH3CH3CH3O
1323	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5O	butoxy
1324	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5O	allyloxy
1325	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5O	CH≡CCH2O
1326	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5O	2-butynyl
							oxy
1327	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5O	3-butynyl
							oxy
1328	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5O	NCCH2O
1329	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5O	CH3S
1330	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	C2H5O	CF3O
1331	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	propoxy	propoxy
1332	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	propoxy	(CH3)2CHO
1333	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	propoxy	cyclopropyl
							methoxy
1334	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	propoxy	butoxy
1335	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	propoxy	allyloxy
1336	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	propoxy	CH≡CCH2O
1337	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	propoxy	2-butynyl
							oxy
1338	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	propoxy	3-butynyl
							oxy
1339	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	propoxy	NCCH2O
1340	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	propoxy	CH3S
1341	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	propoxy	CF3O
1342	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	propoxy	CCl≡CCH2O
1343	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	(CH3)2CHO	CH≡CCH2O
1344	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	cyclopropyl-	CH≡CCH2O
						methoxy
1345	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	butoxy	CH≡CCH2O
1346	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	allyloxy	CH≡CCH2O
1347	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH≡CCH2O	CH≡CCH2O
1348	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	2-butynyl	CH≡CCH2O
						oxy
1349	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	3-butynyl	CH≡CCH2O
						oxy
1350	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	NCCH2O	CH≡CCH2O
1351	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3S	CH≡CCH2O
1352	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CF3O	CH≡CCH2O
1353	CHF2O	4-CH3C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1354	CHF2O	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1355	CHF2O	4-ClC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1356	CHF2O	4-BrC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1357	CHF2O	4-CF3C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1358	CHF2O	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1359	CHF2O	4-CF3OC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1360	CHF2O	3,4-(CH2)3C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1361	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1362	CH2FO	4-CH3C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1363	CF3O	4-CH3C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1364	CH≡CCH2O	4-CH3C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1365	CH2FO	4-ClC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1366	CF3O	4-ClC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1367	CH≡CCH2O	4-ClC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1368	CH2FO	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1369	CF3O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1370	CH≡CCH2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1371	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3O	OH
1372	CH2FO	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1373	CF3O	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1374	CH≡CCH2O	4-C2H5C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1375	CH2FO	4-BrC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1376	CF3O	4-BrC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1377	CH≡CCH2O	4-BrC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1378	CH2FO	4-CF3C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1379	CF3O	4-CF3C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1380	CH≡CCH2O	4-CF3C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1381	CH2FO	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1382	CF3O	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1383	CH≡CCH2O	4-CH3OC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1384	CH2FO	4-CF3OC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1385	CF3O	4-CF3OC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1386	CH≡CCH2O	4-CF3OC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1387	CH2FO	C6H5	O	H	CH2CH2	CH3O	CH≡CCH2O
1388	CHF2O	C6H5	O	H	CH2CH2	CH3O	CH≡CCH2O
1389	CF3O	C6H5	O	H	CH2CH2	CH3O	CH≡CCH2O
1390	CH≡CCH2O	C6H5	O	H	CH2CH2	CH3O	CH≡CCH2O
1391	CH2FO	4-FC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1392	CHF2O	4-FC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1393	CF3O	4-FC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1394	CH≡CCH2O	4-FC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1395	CH2FO	4-CH3CH2CH2C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1396	CHF2O	4-CH3CH2CH2C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1397	CF3O	4-CH3CH2CH2C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1398	CH≡CCH2O	4-CH3CH2CH2C6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1399	CH2FO	4-(CH3)2CHC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1400	CHF2O	4-(CH3)2CHC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1401	CF3O	4-(CH3)2CHC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1402	CH≡CCH2O	4-(CH3)2CHC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1403	CH2FO	4-cyclopropylphenyl	O	H	CH2CH2	CH3O	CH≡CCH2O
1404	CHF2O	4-cyclopropylphenyl	O	H	CH2CH2	CH3O	CH≡CCH2O
1405	CF3O	4-cyclopropylphenyl	O	H	CH2CH2	CH3O	CH≡CCH2O
1406	CH≡CCH2O	4-cyclopropylphenyl	O	H	CH2CH2	CH3O	CH≡CCH2O
1407	CH2FO	4-(CH3)3CC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1408	CHF2O	4-(CH3)3CC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1409	CF3O	4-(CH3)3CC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1410	CH≡CCH2O	4-(CH3)3CC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1411	CH2FO	4-CH3SC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1412	CHF2O	4-CH3SC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1413	CF3O	4-CH3SC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1414	CH≡CCH2O	4-CH3SC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1415	CH2FO	4-CH≡CC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1416	CHF2O	4-CH≡CC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1417	CF3O	4-CH≡CC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1418	CH≡CCH2O	4-CH≡CC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1419	CH2FO	4-N≡CC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1420	CHF2O	4-N≡CC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1421	CF3O	4-N≡CC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1422	CH≡CCH2O	4-N≡CC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1423	CH2FO	4-CH2≡CHC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1424	CHF2O	4-CH2≡CHC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1425	CF3O	4-CH2≡CHC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1426	CH≡CCH2O	4-CH2≡CHC6H4	O	H	CH2CH2	CH3O	CH≡CCH2O
1427	CHF2O	3,4-F2C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1428	CH≡CCH2O	3,4-F2C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1429	CHF2O	3,4-Cl2C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1430	CH≡CCH2O	3,4-Cl2C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1431	CHF2O	3,4-(CH3)2C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1432	CH≡CCH2O	3,4-(CH3)2C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1433	CHF2O	3-F-4-CH3C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1434	CH≡CCH2O	3-F-4-CH3C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1435	CHF2O	3-Cl-4-CH3C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1436	CH≡CCH2O	3-Cl-4-CH3C6H3	O	H	CH2CH2	CH3O CH2	CH≡CCH2O
1437	CHF2O	4-Cl-3-FC6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1438	CH≡CCH2O	4-Cl-3-FC6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1439	CHF2O	3,4-Cl2C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1440	CH≡CCH2O	3,4-Cl2C6H3	O	H	CH2CH2	CH3O	CH≡CCH2O
1441	CHF2O	3-Cl-4-CH3C6H3	O	H	CH(CH3)CH2	CH3O	CH≡CCH2O
1442	CH≡CCH2O	3-Cl-4-CH3C6H3	O	H	CH(CH3)CH2	CH3O	CH≡CCH2O
1443	CHF2O	3,4-Cl2C6H3	O	H	CH(CH3)CH2	CH3O	CH≡CCH2O
1444	CH≡CCH2O	3,4-Cl2C6H3	O	H	CH(CH3)CH2	CH3O	CH≡CCH2O
1445	CHF2O	4-CH3C6H4	S	H	CH2CH2	CH3O	CH≡CCH2O
1446	CHF2O	4-ClC6H4	S	H	CH2CH2	CH3O	CH≡CCH2O
1447	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	Cl	CH3O
1448	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3	CH3O
1449	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	CH3CH2	CH3O
1450	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2	OCH2CH2O
1451	CHF2O	4-CH3C6H4	O	H	CH2CH2	CH3O	C6H5CH2O
1452	CHF2O	4-CH3C6H4	O	H	CH2CH2	CH3O	OH
1453	CHF2O	4-ClC6H4	O	H	CH2CH2	CH3O	C6H5CH2O
1454	CHF2O	4-ClC6H4	O	H	CH2CH2	CH3O	OH
1455	CH≡CCH2O	4-CH3C6H4	O	H	CH2CH2	CH3O	C6H5CH2O
1456	CH≡CCH2O	4-CH3C6H4	O	H	CH2CH2	CH3O	OH
1457	CH≡CCH2O	4-ClC6H4	O	H	CH2CH2	CH3O C6H5	CH2O
1458	CH≡CCH2O	4-ClC6H4	O	H	CH2CH2	CH3O	OH
1459	CHF2O	4-CH3C6H4	O	CH3	CH2CH2	CH3O	CH≡CCH2O
1460	CHF2O	4-CH3C6H4	O	ethyl	CH2CH2	CH3O	CH≡CCH2O
1461	CHF2O	4-CH3C6H4	O	propyl	CH2CH2	CH3O	CH≡CCH2O
1462	CHF2O	4-ClC6H4	O	CH3	CH2CH2	CH3O	CH≡CCH2O
1463	CHF2O	3,4-(CH2)4C6H3	O	CH3	CH2CH2	CH3O	CH≡CCH2O
1464	CHF2O	3,4-(CH2)4C6H3	O	H	CH(CH3)CH2	CH3O	CH3O
1465	CHF2O	4-CH3C6H4	O	H	CH(CH3)CH2	CH3O	CH≡CCH2O
1466	CHF2O	4-ClC6H4	O	H	CH(CH3)CH2	CH3O	CH≡CCH2O
1467	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH(CH3)	CH3O	CH3O
1468	CHF2O	4-CH3C6H4	O	H	CH2CH(CH3)	CH3O	CH≡CCH2O
1469	CHF2O	4-ClC6H4	O	H	CH2CH(CH3)	CH3O	CH≡CCH2O
1470	CHF2O	4-CH3C6H4	O	H	CH2CHF	CH3O	CH≡CCH2O
1471	CHF2O	4-CH3C6H4	O	H	CH2CHCl	CH3O	CH≡CCH2O
1472	CHF2O	4-CH3C6H4	O	H	CH2CH(OCH3)	CH3O	CH≡CCH2O
1473	CHF2O	4-CH3C6H4	O	H	CH2CH(CN)	CH3O	CH≡CCH2O
1474	CHF2O	4-CH3C6H4	O	H	CH(CN)CH2	CH3O	CH≡CCH2O
1475	CHF2O	3,4-(CH2)4C6H3	O	H	CH2CH2CH2	CH3O	CH3O
1476	CHF2O	4-CH3C6H4	O	H	CH2CH2CH2	CH3O	CH3O
1477	CHF2O	4-CH3C6H4	O	H	CH2CH2CH2	CH3O	CH≡CCH2O
1478	CHF2O	4-ClC6H4	O	H	CH2CH2CH2	CH3O	CH≡CCH2O
2001	CH2FO	2-thienyl	O	H	CH2CH2	CH3O	CH3O
2002	CHF2O	2-thienyl	O	H	CH2CH2	CH3O	CH3O
2003	CF3O	2-thienyl	O	H	CH2CH2	CH3O	CH3O
2004	CH2FO	3-thienyl	O	H	CH2CH2	CH3O	CH3O
2005	CHF2O	3-thienyl	O	H	CH2CH2	CH3O	CH3O
2006	CF3O	3-thienyl	O	H	CH2CH2	CH3O	CH3O
2007	CH2FO	2-(4-methylthienyl)	O	H	CH2CH2	CH3O	CH3O
2008	CHF2O	2-(4-methylthienyl)	O	H	CH2CH2	CH3O	CH3O
2009	CF3O	2-(4-methylthienyl)	O	H	CH2CH2	CH3O	CH3O
2010	CH2FO	2-(5-methylthienyl)	O	H	CH2CH2	CH3O	CH3O
2011	CHF2O	2-(5-methylthienyl)	O	H	CH2CH2	CH3O	CH3O
2012	CF3O	2-(5-methylthienyl)	O	H	CH2CH2	CH3O	CH3O
2013	CH2FO	2-(4-chlorothienyl)	O	H	CH2CH2	CH3O	CH3O
2014	CHF2O	2-(4-chlorothienyl)	O	H	CH2CH2	CH3O	CH3O
2015	CF3O	2-(4-chlorothienyl)	O	H	CH2CH2	CH3O	CH3O
2016	CH2FO	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH3O
		thienyl)
2017	CHF2O	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH3O
		thienyl)
2018	CF3O	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH3O
		thienyl)
2019	CH2FO	2-furyl	O	H	CH2CH2	CH3O	CH3O
2020	CHF2O	2-furyl	O	H	CH2CH2	CH3O	CH3O
2021	CF3O	2-furyl	O	H	CH2CH2	CH3O	CH3O
2022	CH2FO	3-furyl	O	H	CH2CH2	CH3O	CH3O
2023	CHF2O	3-furyl	O	H	CH2CH2	CH3O	CH3O
2024	CF3O	3-furyl	O	H	CH2CH2	CH3O	CH3O
2025	CH2FO	2-(5-methyfuryl)	O	H	CH2CH2	CH3O	CH3O
2026	CHF2O	2-(5-methyfuryl)	O	H	CH2CH2	CH3O	CH3O
2027	CF3O	2-(5-methyfuryl)	O	H	CH2CH2	CH3O	CH3O
2028	CH2FO	2-pyridyl	O	H	CH2CH2	CH3O	CH3O
2029	CHF2O	2-pyridyl	O	H	CH2CH2	CH3O	CH3O
2030	CF3O	2-pyridyl	O	H	CH2CH2	CH3O	CH3O
2031	CH2FO	2-(5-methylpyridyl)	O	H	CH2CH2	CH3O	CH3O
2032	CHF2O	2-(5-methylpyridyl)	O	H	CH2CH2	CH3O	CH3O
2033	CF3O	2-(5-methylpyridyl)	O	H	CH2CH2	CH3O	CH3O
2034	CH2FO	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH3O
		pyridyl)
2035	CHF2O	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH3O
		pyridyl)
2036	CF3O	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH3O
		pyridyl)
2037	CH2FO	2-pyrimidinyl	O	H	CH2CH2	CH3O	CH3O
2038	CHF2O	2-pyrimidinyl	O	H	CH2CH2	CH3O	CH3O
2039	CF3O	2-pyrimidinyl	O	H	CH2CH2	CH3O	CH3O
2040	CH2FO	4-pyrimidinyl	O	H	CH2CH2	CH3O	CH3O
2041	CHF2O	4-pyrimidinyl	O	H	CH2CH2	CH3O	CH3O
2042	CF3O	4-pyrimidinyl	O	H	CH2CH2	CH3O	CH3O
2043	CH2FO	2-pyrazinyl	O	H	CH2CH2	CH3O	CH3O
2044	CHF2O	2-pyrazinyl	O	H	CH2CH2	CH3O	CH3O
2045	CF3O	2-pyrazinyl	O	H	CH2CH2	CH3O	CH3O
2046	CH2FO	2-thiazolyl	O	H	CH2CH2	CH3O	CH3O
2047	CHF2O	2-thiazolyl	O	H	CH2CH2	CH3O	CH3O
2048	CF3O	2-thiazolyl	O	H	CH2CH2	CH3O	CH3O
2049	CH2FO	2-(5-methylthiazolyl)	O	H	CH2CH2	CH3O	CH3O
2050	CHF2O	2-(5-methylthiazolyl)	O	H	CH2CH2	CH3O	CH3O
2051	CF3O	2-(5-methylthiazolyl)	O	H	CH2CH2	CH3O	CH3O
2052	CH2FO	2-(3-methylthiazolyl)	O	H	CH2CH2	CH3O	CH3O
2053	CHF2O	2-(3-methylthiazolyl)	O	H	CH2CH2	CH3O	CH3O
2054	CF3O	2-(3-methylthiazolyl)	O	H	CH2CH2	CH3O	CH3O
2055	CH2FO	1-(4-methylpyrazolyl)	O	H	CH2CH2	CH3O	CH3O
2056	CHF2O	1-(4-methylpyrazolyl)	O	H	CH2CH2	CH3O	CH3O
2057	CF3O	1-(4-methylpyrazolyl)	O	H	CH2CH2	CH3O	CH3O
2058	CH2FO	2-thienyl	O	H	CH2CH2	CH3CH2O	CH3O
2059	CHF2O	2-thienyl	O	H	CH2CH2	CH3CH2O	CH3O
2060	CF3O	2-thienyl	O	H	CH2CH2	CH3CH2O	CH3O
2061	CH2FO	3-thienyl	O	H	CH2CH2	CH3CH2O	CH3O
2062	CHF2O	3-thienyl	O	H	CH2CH2	CH3CH2O	CH3O
2063	CF3O	3-thienyl	O	H	CH2CH2	CH3CH2O	CH3O
2064	CH2FO	2-thienyl	S	H	CH2CH2	CH3O	CH3O
2065	CHF2O	2-thienyl	S	H	CH2CH2	CH3O	CH3O
2066	CF3O	2-thienyl	S	H	CH2CH2	CH3O	CH3O
2067	CH2FO	3-thienyl	S	H	CH2CH2	CH3O	CH3O
2068	CHF2O	3-thienyl	S	H	CH2CH2	CH3O	CH3O
2069	CF3O	3-thienyl	S	H	CH2CH2	CH3O	CH3O
2070	CH2FO	2-(5-methylpyridyl)	O	H	CH2CH2	CH3CH2O	CH3O
2071	CHF2O	2-(5-methylpyridyl)	O	H	CH2CH2	CH3CH2O	CH3O
2072	CF3O	2-(5methylpyridyl)	O	H	CH2CH2	CH3CH2O	CH3O
2073	CH2FO	1-naphthyl	O	H	CH2CH2	CH3O	CH3O
2074	CHF2O	1-naphthyl	O	H	CH2CH2	CH3O	CH3O
2075	CF3O	1-naphthyl	O	H	CH2CH2	CH3O	CH3O
2076	CH2FO	2-naphthyl	O	H	CH2CH2	CH3O	CH3O
2077	CHF2O	2-naphthyl	O	H	CH2CH2	CH3O	CH3O
2078	CF3O	2-naphthyl	O	H	CH2CH2	CH3O	CH3O
2079	CH2FO	2-naplithyl	S	H	CH2CH2	CH3O	CH3O
2080	CHF2O	2-naphthyl	S	H	CH2CH2	CH3O	CH3O
2081	CF3O	2-naphthyl	S	H	CH2CH2	CH3O	CH3O
2082	CH2FO	5-benzofuryl	O	H	CH2CH2	CH3O	CH3O
2083	CHF2O	5-benzofuryl	O	H	CH2CH2	CH3O	CH3O
2084	CF3O	5-benzofuryl	O	H	CH2CH2	CH3O	CH3O
2085	CH2FO	6-benzofuryl	O	H	CH2CH2	CH3O	CH3O
2086	CHF2O	6-benzofuryl	O	H	CH2CH2	CH3O	CH3O
2087	CF3O	6-benzofuryl	O	H	CH2CH2	CH3O	CH3O
2088	CH2FO	5-benzothienyl	O	H	CH2CH2	CH3O	CH3O
2089	CHF2O	5-benzothienyl	O	H	CH2CH2	CH3O	CH3O
2090	CF3O	5-benzothienyl	O	H	CH2CH2	CH3O	CH3O
2091	CH2FO	6-benzothienyl	O	H	CH2CH2	CH3O	CH3O
2092	CHF2O	6-benzothienyl	O	H	CH2CH2	CH3O	CH3O
2093	CF3O	6-benzothienyl	O	H	CH2CH2	CH3O	CH3O
2094	CH2FO	5-benzothiazolyl	O	H	CH2CH2	CH3O	CH3O
2095	CHF2O	5-benzothiazolyl	O	H	CH2CH2	CH3O	CH3O
2096	CF3O	5-benzothiazolyl	O	H	CH2CH2	CH3O	CH3O
2097	CH2FO	6-benzothiazolyl	O	H	CH2CH2	CH3O	CH3O
2098	CHF2O	6-benzothiazolyl	O	H	CH2CH2	CH3O	CH3O
2099	CF3O	6-benzothiazolyl	O	H	CH2CH2	CH3O	CH3O
2100	CH2FO	2-benzothiazolyl	O	H	CH2CH2	CH3O	CH3O
2101	CHF2O	2-benzothiazolyl	O	H	CH2CH2	CH3O	CH3O
2102	CF3O	2-benzothiazolyl	O	H	CH2CH2	CH3O	CH3O
2103	CH2FO	2-benzothienyl	O	H	CH2CH2	CH3O	CH3O
2104	CHF2O	2-benzothienyl	O	H	CH2CH2	CH3O	CH3O
2105	CF3O	2-benzothienyl	O	H	CH2CH2	CH3O	CH3O
2106	CH2FO	2-benzofuryl	O	H	CH2CH2	CH3O	CH3O
2107	CHF2O	2-benzofuryl	O	H	CH2CH2	CH3O	CH3O
2108	CF3O	2-benzofuryl	O	H	CH2CH2	CH3O	CH3O
2109	CH2FO	3-benzofuryl	O	H	CH2CH2	CH3O	CH3O
2110	CHF2O	3-benzofuryl	O	H	CH2CH2	CH3O	CH3O
2111	CF3O	3-benzofuryl	O	H	CH2CH2	CH3O	CH3O
2112	CH2FO	benzo-1,2,3-thiazol-	O	H	CH2CH2	CH3O	CH3O
		5-yl
2113	CHF2O	benzo-1,2,3-thiazol-	O	H	CH2CH2	CH3O	CH3O
		5-yl
2114	CF3O	benzo-1,2,3-thiazol-	O	H	CH2CH2	CH3O	CH3O
		5-yl
2115	CH2FO	2-benzimidazolyl	O	H	CH2CH2	CH3O	CH3O
2116	CHF2O	2-benzimidazolyl	O	H	CH2CH2	CH3O	CH3O
2117	CF3O	2-benzimidazolyl	O	H	CH2CH2	CH3O	CH3O
2118	CH2FO	2-(1-methylbenzimi-	O	H	CH2CH2	CH3O	CH3O
		dazolyl)
2119	CHF2O	2-(1-methylbenzimi-	O	H	CH2CH2	CH3O	CH3O
		dazolyl)
2120	CF3O	2-(1-methylbenzimi-	O	H	CH2CH2	CH3O	CH3O
		dazolyl)
2121	CH≡CCH2O	2-(5-methylthienyl)	O	H	CH2CH2	CH3O	CH3O
2122	CH≡CCH2O	2-(5-trifluorometh-	O	H	CH2CH2	CH3O	CH3O
		ylthienyl)
2123	CH≡CCH2O	2-(5-methylfuryl)	O	H	CH2CH2	CH3O	CH3O
2124	CH≡CCH2O	2-(5-trifluorometh-	O	H	CH2CH2	CH3O	CH3O
		ylpyridyl)
2125	CH≡CCH2O	2-naphthyl	O	H	CH2CH2	CH3O	CH3O
2126	CH2FO	2-thienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2127	CHF2O	2-thienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2128	CF3O	2-thienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2129	CH2FO	3-thienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2130	CHF2O	3-thienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2131	CF3O	3-thienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2132	CH2FO	2-(4-methylthienyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2133	CHF2O	2-(4-methylthienyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2134	CF3O	2-(4-methylthienyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2135	CH2FO	2-(5-methylthienyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2136	CHF2O	2-(5-methylthienyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2137	CF3O	2-(5-methylthienyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2138	CH2FO	2-(5-chlorothienyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2139	CHF2O	2-(5-chlorothienyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2140	CF3O	2-(5-chlorothienyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2141	CH2FO	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH≡CCH2O
		thienyl)
2142	CHF2O	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH≡CCH2O
		thienyl)
2143	CF3O	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH≡CCH2O
		thienyl)
2144	CH2FO	2-furyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2145	CHF2O	2-furyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2146	CF3O	2-furyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2147	CH2FO	3-furyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2148	CHF2O	3-furyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2149	CF3O	3-furyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2150	CH2FO	2-(5-methylfuryl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2151	CHF2O	2-(5-methylfuryl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2152	CF3O	2-(5-methylfuryl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2153	CH2FO	2-pyridyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2154	CHF2O	2-pyridyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2155	CF3O	2-pyridyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2156	CH2FO	2-(5-methylpyridyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2157	CHF2O	2-(5-methylpyridyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2158	CF3O	2-(5-methylpyridyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2159	CH2FO	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH≡CCH2O
		pyridyl)
2160	CHF2O	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH≡CCH2O
		pyridyl)
2161	CF3O	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH≡CCH2O
		pyridyl)
2162	CH2FO	2-pyrimidinyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2163	CHF2O	2-pyrimidinyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2164	CF3O	2-pyrimidinyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2165	CH2FO	4-pyrimidinyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2166	CHF2O	4-pyrimidinyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2167	CF3O	4-pyrimidinyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2168	CH2FO	2-pyrazinyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2169	CHF2O	2-pyrazinyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2170	CF3O	2-pyrazinyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2171	CH2FO	2-thiazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2172	CHF2O	2-thiazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2173	CF3O	2-thiazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2174	CH2FO	2-(5-methylthiazolyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2175	CHF2O	2-(5-methylthiazolyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2176	CF3O	2-(5-methylthiazolyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2177	CH2FO	3-(3-methylpyrazolyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2178	CHF2O	3-(3-methylpyrazolyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2179	CF3O	3-(3-methylpyrazolyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2180	CH2FO	1-(4-methylpyrazolyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2181	CHF2O	1-(4-methylpyrazolyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2182	CF3O	1-(4-methylpyrazolyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2183	CH2FO	2-thienyl	O	H	CH(CH3)CH2	CH3O	CH3O
2184	CHF2O	2-thienyl	O	H	CH(CH3)CH2	CH3O	CH3O
2185	CF3O	2-thienyl	O	H	CH(CH3)CH2	CH3O	CH3O
2186	CH2FO	3-thienyl	O	H	CH(CH3)CH2	CH3O	CH3O
2187	CHF2O	3-thienyl	O	H	CH(CH3)CH2	CH3O	CH3O
2188	CF3O	3-thienyl	O	H	CH(CH3)CH2	CH3O	CH3O
2189	CH2FO	2-naphthyl	O	H	CH(CH3)CH2	CH3O	CH3O
2190	CHF2O	2-naphthyl	O	H	CH(CH3)CH2	CH3O	CH3O
2191	CF3O	2-naphthyl	O	H	CH(CH3)CH2	CH3O	CH3O
2192	CH2FO	2-naphthyl	O	CH3	CH2CH2	CH3O	CH3O
2193	CHF2O	2-naphthyl	O	CH3	CH2CH2	CH3O	CH3O
2194	CF3O	2-naphthyl	O	CH3	CH2CH2	CH3O	CH3O
2195	CH2FO	2-thienyl	O	CH3	CH2CH2	CH3O	CH3O
2196	CHF2O	2-thienyl	O	CH3	CH2CH2	CH3O	CH3O
2197	CF3O	2-thienyl	O	CH3	CH2CH2	CH3O	CH3O
2198	CH2FO	1-naphthyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2199	CHF2O	1-naphthyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2200	CF3O	1-naphthyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2201	CH2FO	2-naphthyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2202	CHF2O	2-naphthyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2203	CF3O	2-naphthyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2204	CH2FO	2-naphthyl	S	H	CH2CH2	CH3O	CH≡CCH2O
2205	CHF2O	2-naphthyl	S	H	CH2CH2	CH3O	CH≡CCH2O
2206	CF3O	2-naphthyl	S	H	CH2CH2	CH3OCH2	CH≡CCH2O
2207	CH2FO	5-benzofuryl	O	H	CH2CH2	CH3O	CH≡CCH2O
2208	CHF2O	5-benzofuryl	O	H	CH2CH2	CH3O	CH≡CCH2O
2209	CF3O	5-benzofuryl	O	H	CH2CH2	CH3O	CH≡CCH2O
2210	CH2FO	6-benzofuryl	O	H	CH2CH2	CH3O	CH≡CCH2O
2211	CHF2O	6-benzofuryl	O	H	CH2CH2	CH3O	CH≡CCH2O
2212	CF3O	6-benzofuryl	O	H	CH2CH2	CH3O	CH≡CCH2O
2213	CH2FO	5-benzothienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2214	CHF2O	5-benzothienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2215	CF3O	5-benzothienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2216	CH2FO	6-benzothienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2217	CHF2O	6-benzothienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2218	CF3O	6-benzothienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2219	CH2FO	5-benzothiazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2220	CHF2O	5-benzothiazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2221	CF3O	5-benzothiazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2222	CH2FO	6-benzothiazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2223	CHF2O	6-benzothiazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2224	CF3O	6-benzothiazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2225	CH2FO	2-benzothiazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2226	CHF2O	2-benzothiazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2227	CF3O	2-benzothiazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2228	CH2FO	2-benzothienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2229	CHF2O	2-benzothienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2230	CF3O	2-benzothienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2231	CH2FO	3-benzothienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2232	CHF2O	3-benzothienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2233	CF3O	3-benzothienyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2234	CH2FO	2-benzofuryl	O	H	CH2CH2	CH3O	CH≡CCH2O
2235	CHF2O	2-benzofuryl	O	H	CH2CH2	CH3O	CH≡CCH2O
2236	CF3O	2-benzofuryl	O	H	CH2CH2	CH3O	CH≡CCH2O
2237	CH2FO	3-benzofuryl	O	H	CH2CH2	CH3O	CH≡CCH2O
2238	CHF2O	3-benzofuryl	O	H	CH2CH2	CH3O	CH≡CCH2O
2239	CF3O	3-benzofuryl	O	H	CH2CH2	CH3O	CH≡CCH2O
2240	CH2FO	benzo-1,2,3-thiazol-	O	H	CH2CH2	CH3O	CH≡CCH2O
		5-yl
2241	CHF2O	benzo-1,2,3-thiazol-	O	H	CH2CH2	CH3O	CH≡CCH2O
		5-yl
2242	CF3O	benzo-1,2,3-thiazol-	O	H	CH2CH2	CH3O	CH≡CCH2O
		5-yl
2243	CH2FO	2-benzimidazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2244	CHF2O	2-benzimidazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2245	CF3O	2-benzimidazolyl	O	H	CH2CH2	CH3O	CH≡CCH2O
2246	CF3S	2-thienyl	O	H	CH2CH2	CH3O	CH3O
2247	CH2FO	2-(1-methylbenzimidazolyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2248	CHF2O	2-(1-methylbenzimidazolyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2249	CF3O	2-(1-methylbenzimidazolyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2250	CH≡CCH2O	2-(5-methylthienyl)	O	H	CH2CH2	CH3O	CH≡CCH2O
2251	CH≡CCH2O	2-(5-trifluoromethyl	O	H	CH2CH2CH3O	CH3O
		thienyl)
2252	CH≡CCH2O	2-(5-methylfuryl)	O	H	CH2CH2	CH3O	CH3O
2253	CH≡CCH2O	2-(5-trifluoromethyl	O	H	CH2CH2	CH3O	CH3O
		pyridyl)
2254	CH≡CCH2O	2-naphthyl	O	H	CH2CH2	CH3O	CH3O

[0248] Formulation examples are given below. Parts represent parts by weight. The numbers of the present compounds are represented by the above-mentioned numbers.

Formulation Example 1

[0249] Fifty parts of each of the present compounds 1001-1478 and 2001-2254, 3 parts of calcium ligninsulfonate, 2 parts of magnesium laurylsulfate and 45 parts of synthetic hydrated silica are pulverized and mixed well to give wettable powders of each compound.

Formulation Example 2

[0250] Twenty parts of each of the present compounds 1001-1478 and 2001-2254 and 1.5 parts of sorbitan trioleate are mixed with 28.5 parts of an aqueous solution containing 2 parts of polyvinyl alcohol, and wet-pulverized finely. To the obtained mixture, 40 parts of an aqueous solution containing 0.05 part of xanthan gum and 0.1 part of aluminium magnesium silicate is added and further 10 parts of propylene glycol are added to give a flowable of each compound.

Formulation Example 3

[0251] Two parts of each of the present compounds 1001-1478 and 2001-2254, 88 parts of kaolin clay and 10 parts of talc are pulverized and mixed well to give dusts of each compound.

Formulation Example 4

[0252] Five parts of each of the present compounds 1001-1478 and 2001-2254, 14 parts of polyoxyethylenestyryl phenyl ether, 6 parts of calcium dodecylbenzenesulfonate and 75 parts of xylene are mixed well to give emulsifiable concentrates of each compound.

Formulation Example 5

[0253] Two parts of each of the present compounds 1001-1478 and 2001-2254, 1 part of synthetic hydrated silica, 2 parts of calcium ligninsulfonate, 30 parts of bentonite and 65 parts of kaolin clay are pulverized and mixed well, and water is added thereto and kneeded, granulated and dried to give granules of each compound.

Formulation Example 6

[0254] Ten parts of each of the present compounds 1001-1478 and 2001-2254, 35 parts of white carbon (calsium silicate) containing 50% of ammonium polyoxyethylenealkyl ether sulfate and 55 parts of water are mixed and wet pulverized finely to give a flowable of each compound.

[0255] Next, usefulness of the present compounds for controlling plant diseases is shown by test examples. The present compounds are represented by the numbers referred to in the above table.

[0256] The control effect of the present compounds was evaluated by visually observing the area of a lesion on a sample plant in investigation and comparing the area of a lesion in a non-treatment district and the area of a lesion in a district treated with the present compound.

Test Example 1

[0257] Sand loam was compacted in a plastic pot, a grape (variety: Berry A) was seeded and grown in a green house for 40 days. The present compounds 1004, 1005, 1006, 1016, 1017, 1020, 1023, 1026, 1029, 1065, 1103, 1104, 1143, 1160, 1182, 1196, 1197, 1223, 1232, 1241, 1251, 1258, 1266, 1268, 1271, 1274, 1281, 1282, 1305, 1320, 1371, 2077 and 2133 were formulated into flowables according to formulation example 6, then, diluted with water to provide given concentration (200 ppm), and these were sprayed onto stems and leaves so as to give sufficient adhesion on the surface of grape leaves. After spraying, the plant was air-dried, and a suspension of zoosporangiua of Plasmopara viticola was inoculated by spraying. After inoculation, the plant was first left for one day at 23° C. under high humidity, then further left for 6 days in the green house, then the control effect was checked. As a result, the lesion areas on plants in the treatment districts using the present compounds were not more than 10% of the lesion area of a non-treatment district.

Test Example 2

[0258] Sand loam was compacted in a plastic pot, a grape (variety: Berry A) was seeded and grown in a green house for 40 days. The present compounds 1259, 1284, 1353, 1355, 1360, 1367, 1445, 1447 and 1450 were formulated into flowables according to formulation example 6, then, diluted with water to provide given concentration (50 ppm), and these were sprayed onto stems and leaves so as to give sufficient adhesion on the surface of grape leaves. After spraying, the plant was air-dried, and a suspension of zoosporangiua of Plasmopara viticola was inoculated by spraying. After inoculation, the plant was first left for one day at 23° C. under high humidity, then further left for 6 days in the green house, then the control effect was checked. As a result, the lesion areas on plants in the treatment districts using the present compounds were not more than 10% of the lesion area of a non-treatment district.

Test Example 3

[0259] Sand loam was compacted in a plastic pot, a grape (variety: Berry A) was seeded and grown in a green house for 40 days. The present compounds 1354, 1357, 1358, 1364, 1388, 1392, 1429 and 2202 were formulated into flowables according to formulation example 6, then, diluted with water to provide given concentration (12.5 ppm), and these were sprayed onto stems and leaves so as to give sufficient adhesion on the surface of grape leaves. After spraying, the plant was air-dried, and a suspension of zoosporangiua of Plasmopara viticola was inoculated by spraying. After inoculation, the plant was first left for one day at 23° C. under high humidity, then further left for 6 days in the green house, then the control effect was checked. As a result, the lesion areas on plants in the treatment districts using the present compounds were not more than 10% of the lesion area of a non-treatment district.

Test Example 4

[0260] Sand loam was compacted in a plastic pot, a tomato (variety: Ponterosa) was seeded and grown in a green house for 20 days. The present compounds 1004, 1005, 1006, 1016, 1017, 1020, 1023, 1026, 1029, 1034, 1065, 1103, 1104, 1122, 1143, 1160, 1182, 1185, 1196, 1197, 1223, 1124, 1127, 1232, 1241, 1251, 1258, 1259, 1268, 1269, 1274, 1281, 1282, 1284, 1299, 1320, 1353, 1354, 1358, 1360, 1388, 1367, 1392, 1429, 1445, 1448, 1450, 1465, 1476, 2077 and 2133 were formulated into flowables according to formulation example 6, then, diluted with water to provide given concentration (500 ppm), and these were sprayed onto stems and leaves so as to give sufficient adhesion on the surface of tomato leaves. After spraying, the plant was air-dried, and a suspension of zoosporangiua of Phytophthora infestans was inoculated by spraying. After inoculation, the plant was first left for one day at 23° C. under high humidity, then further left for 4 days in the green house, then the control effect was checked. As a result, the lesion areas on plants in the treatment districts using the present compounds were not more than 10% of the lesion area of a non-treatment district.

Industrial Applicability

[0261] The present compound has an excellent efficacy for controlling plant diseases and is useful as an active ingredient of fungicide, especially agricultural and horticultural fungicide.

Claims

1. An amide compound given by formula [I]:

2. An amide compound according to claim 1, wherein Ar is an aromatic hydrocarbyl group or aromatic heterocyclic group which may be substituted by at least one selected from halogen, amino, hydroxy, cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, cyano C1-C9 alkyl, C2-C10 alkenyl, C2-C10 haloalkenyl, C2-C10 alkynyl, C2-C10 haloalkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C3-C10 alkenyloxy, C3-C10 haloalkenyloxy, C3-C10 alkynyloxy, C3-C10 haloalkynyloxy, C3-C10 cycloalkoxy, cyano C1-C9 alkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, C2-C10 (alkoxycarbonyl) and tri(C1-C6 alkyl)silyl.

3. An amide compound according to claim 2, wherein Ar is phenyl, naphthyl, thienyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, thiadiazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolidinyl, benzofuryl, benzothienyl, indolyl, benzothiazolyl, benzimidazolyl, benzopyrazolyl, quinolyl, isoquinolyl, pyrazolopyrimidinyl, imidazopyrimidinyl, thiophenopyrimidinyl, thiazolopyrimidinyl, pyrazolopyridyl, imidazopyridyl, thiophenopyridyl or thiazolopyridyl which may be substituted by at least one selected from halogen, amino, hydroxy, cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, cyano C1-C9 alkyl, C2-C10 alkenyl, C2-C10 haloalkenyl, C2-C10 alkynyl, C2-C10 haloalkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C3-C10 alkenyloxy, C3-C10 haloalkenyloxy, C3-C10 alkynyloxy, C3-C10 haloalkynyloxy, C3-C10 cycloalkoxy, cyano C1-C9 alkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, C2-C10 (alkoxycarbonyl) and tri(C1-C6 alkyl)silyl.

4. An amide compound according to claim 2, wherein Ar is phenyl or naphthyl which may be substituted by at least one selected from halogen, amino, hydroxy, cyano, nitro, C1-C10 alkyl, C1-C10 haloalkyl, cyano C1-C9 alkyl, C2-C10 alkenyl, C2-C10 haloalkenyl, C2-C10 alkynyl, C2-C10 haloalkynyl, C3-C6 cycloalkyl, C3-C6 cycloalkenyl, C1-C10 alkoxy, C1-C10 haloalkoxy, C3-C10 alkenyloxy, C3-C10 haloalkenyloxy, C3-C10 alkynyloxy, C3-C10 haloalkynyloxy, C3-C10 cycloalkoxy, cyano C1-C9 alkoxy, C1-C10 alkylthio, C1-C10 haloalkylthio, C2-C10 (alkoxycarbonyl) and tri(C1-C6 alkyl)silyl.

5. An amide compound according to claim 2, wherein Ar is phenyl, 4-methylphenyl, 3-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 3-methoxyphenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, 3,4-tetramethylenephenyl, 3,4-trimethylenephenyl, 3,4-dichlorophenyl, 3,4-dimethoxyphenyl or 2-naphthyl.

6. An amide compound according to claim 1, wherein A is an ethylene group.

7. An amide compound according to claim 1, wherein R2 is a hydrogen atom.

8. An amide compound according to claim 1, wherein both of X and Y are oxygen atoms.

9. An amide compound according to claim 1, wherein both of Z1 and Z2 are methoxy.

10. An amide compound according to claim 1, wherein Z1 is methoxy and Z2 is 2-propynyloxy.

11. An amide compound according to claim 1, wherein R1 is a fluoromethyl, difluoromethyl, trifluoromethyl or 2-propynyl.

12. An amide compound according to claim 1, which is N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-(4-methylphenyl)acrylamide, N-[2-(3,4-dimethoxyphenyl) ethyl]-3-difluoromethoxy-2-[2-(5,6,7,8-tetrahydronaphthalen-2-yl)]acrylamide, N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(5,6,7,8-tetrahydronaphthalen-2-yl)acrylamide, N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(4-methyphenyl) acrylamide, N-[2-(3,4-dimethoxyphenyl)ethyl]-3-difluoromethoxy-2- (4-chlorophenyl) acrylamide or N-[2-{3-methoxy-4-(2-propynyloxy)phenyl}ethyl]-3-difluoromethoxy-2-(4-chlorophenyl)acrylamide

13. A fungicide which is characterized by comprising an amide compound described in claim 1 as an active ingredient, and a carrier.

14. A method for controlling plant diseases which is characterized by applying an effective amount of an amide compound described in claim 1 to plants.