Amide compounds and use thereof

Abstract

An amide compound given by formula [I]: wherein R1 represents a C1-C10 haloalkyl and so on, R2 represents a hydrogen and so on, X represents an oxygen or sulfur, Y represents an oxygen or sulfur, Ar represents an aromatic group, A represents an ethylene and so on, and Z1 and Z2 represent alkyl, alkoxy and so on, and a fungicide containing it as an active ingredient.

Description

This application is a 371 of PCT/JP01/05037, filed Jun. 13, 2001.

1. Technical Field

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

2. Background Arts

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

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

wherein R 1 represents a C1-C10 haloalkyl group, C2-C10 haloalkenyl group, C3-C10 haloalkynyl group, C3-C8 halocycloalkyl group or C3-C10 alkynyl group; R 2 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; Z 1 and Z 2 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 Z 1 and Z 2 may represents C2-C6 alkylenedioxy group together, (hereinafter, referred to as the present compound) and fungicide comprising it as an active ingredient.

In the present invention, examples of the C1-C10 haloalkyl group for R 1 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 R 1 .

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.

In the present invention, the ethylene group (—CH 2 CH 2 —) 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 (—CH 2 CH 2 —) is preferable for A.

In the present invention, examples of the C1-C6 alkyl group for Z 1 and Z 2 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 Z 1 and methoxy and 2-propynyloxy for Z 2 .

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.

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.

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.

Production Method A

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

In the above scheme, L 1 represents a leaving group such as chlorine, bromine, iodine, p-toluenesulfonyloxy, methanesulfonyloxy and trifluoromethanesulfonyl; R 11 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 R 2 , X, Y, Ar, A, Z 1 and Z 2 have the same meanings as defined above.

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].

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.

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.

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.

The compound given by formula [I] wherein R 1 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.

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.

In the above scheme, L 3 and L 4 are the same or different and represent alkoxy group such as t-butoxy group; L 2 represents chlorine or bromine atom; and R 2 , Ar A, Z 1 and Z 2 have the same meanings as defined above.

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].

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.

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.

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.

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].

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.

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.

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].

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.

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.

Production Method B

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)

In the above scheme, R 1 , R 2 , X, Ar, A, Z 1 and Z 2 have the same meanings as defined above.

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].

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.

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.

Production Method C

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

In the above scheme, L 5 represents p-toluenesulfonyl, methanesulfonyl or trifluoromethanesulfonyl, and R 1 , R 2 , Y, Ar, A, Z 1 and Z 2 have the same meanings as defined above.

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].

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.

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.

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.

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

In the above scheme, L 5 , R 2 , Ar, A, Z 1 and Z 2 have the same meanings as defined above.

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].

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.

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.

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.

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

wherein L 2 and Ar mean as described above.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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], azinphos-methyl [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)cyclopropanecarboxylate], 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.

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, Sphaerotheca fuliginea, 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

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

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

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).

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

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.

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

Production Example 2

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).

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

Production Example 3

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).

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

Production Example 4

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.

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

Production Example 5

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).

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

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.

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

Production Example 6

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).

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

Production Example 7

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).

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

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 8.20(1H,s), 7.1-7.2(2H,m), 6.8-7.0(4H,m), 6.38(1H,t, J=71.0 Hz), 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=6.8 Hz), 2.52(1H,t,J=2.1 Hz), 2.39(3H,s).

Production Example 8

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).

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

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.1-7.3(2H,m), 6.7-6.9(6H,m), 6.35(1H,t, J=71.7 Hz), 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=6.8 Hz).

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.

1 H-NMR(CDCl 3 , 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=71.6 Hz), 6.08(1H,br), 3.84(3H,s), 3.79(3H,s), 3.6-3.7(2H,m), 2.86(2H,t,J=6.9 Hz).

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.

1 H-NMR(CDCl 3 , 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=71.4 Hz), 6.14(1H,br), 3.86(3H,s), 3.83(3H,s), 3.6-3.7(2H,m), 2.84(2H,t,J=6.9 Hz).

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.

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

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.0-7.2(3H,m), 6.6-6.9(4H,m), 6.35(1H,t, 71.7 Hz), 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).

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.

1 H-NMR(CDCl 3 , 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=70.8 Hz), 6.28(1H,br), 3.8-3.9(6H,m), 3.6-3.7(2H,m), 2.86(2H,t,J=6.7 Hz).

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.

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

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.

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

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.0-7.2(4H,m), 6.7-6.9(4H,m), 6.38(1H,t, J=71.7 Hz), 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=6.8 Hz).

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.

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

Production Example 9

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).

1 H-NMR(CDCl 3 , TMS) δ(ppm): 6.5-7.1(7H,m), 6.38(1H,t,J=72.4 Hz), 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

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).

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

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 6.9-7.0(3H,m), 6.7-6.9(4H,m), 6.53(1H,s), 5.98(1H,d,J=6.4 Hz), 4.51(2H,d,J=6.5 Hz), 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).

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.

1 H-NMR(CDCl 3 , 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

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).

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.65(1H,s), 4.50(2H,d,J=2.6 Hz), 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

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).

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

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 6.99(3H,s), 6.7-6.9(4H,m), 6.37(1H,t,J=71.8 Hz), 6.12(1H,br), 4.06(2H,q,J=8.1 Hz), 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=7.0 Hz).

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 6.9-7.1(3H,m), 6.4-6.9(4H,m), 6.36(1H,t, J=71.9 Hz), 6.05(1H,br), 3.97(2H,t,J=6.8 Hz), 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=7.4 Hz).

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 6.9-7.1(4H,m), 6.7-6.9(3H,m), 6.39(1H,t, J=71.8 Hz), 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).

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.

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

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.

1 H-NMR(CDCl 3 , 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=71.7 Hz), 6.03(1H,br), 4.69(2H,q,J=2.3 Hz), 3.82(3H,s), 3.6-3.7(2H,m), 2.83(2H,t,J=6.9 Hz), 2.7-2.8(4H,m), 1.83(3H,t,J=2.2 Hz), 1.7-1.8(4H,m).

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.0-7.1(4H,m), 6.85(1H,s), 6.7-6.8(2H,m), 6.34(1H,t,J=71.6 Hz), 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)

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.00(3H,s), 6.6-6.9(4H,m), 6.35(1H,t, J=71.7 Hz), 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=6.1 Hz).

Production Example 13

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).

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

Production Example 14

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).

1 H-NMR(CDCl 3 , 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

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).

1 H-NMR(CDCl 3 , 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

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).

1 H-NMR(CDCl 3 , 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=71.6 Hz), 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).

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.01(3H,s), 6.85(1H,s), 6.6-6.8(3H,m), 6.41(1t,J=71.6 Hz), 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).

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 6.9-7.2(4H,m), 6.8-6.9(3H,m), 6.40(1H,t, J=71.6 Hz), 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).

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 6.9-7.0(4H,m), 6.7-6.9(3H,m), 6.34(1H,t, J=71.7 Hz), 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

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).

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.0-7.1(3H,m), 6.84(1H,d,J=3.3 Hz), 6.80(1H,s), 6.6-6.7(2H,m), 6.36(1H,t,J=71.8 Hz), 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

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).

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

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.00(3H,s), 6.7-6.9(4H,m), 6.36(1H,t, J=71.7 Hz), 6.02(1H,br), 4.04(2H,q,J=7.0 Hz), 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=7.0 Hz).

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.

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

Production Example 19

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).

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

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.

1 H-NMR(CDCl 3 , 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=71.6 Hz), 6.06(1H,br), 4.74(2H,d,J=2.4 Hz), 3.83(3H,s), 3.6-3.7(2H,m), 2.8-2.9(6H,m), 2.49(1H,t,J=2.4 Hz), 2.0-2.2(2H,m).

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.

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

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.

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

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.

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

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.

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

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.

1 H-NMR(CDCl 3 , 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=71.3 Hz), 6.17(1H,br), 4.76(2H,d,J=2.4 Hz), 3.85(3H,s), 3.6-3.7(2H,m), 2.85(2H,t,J=6.8 Hz), 2.64(2H,q,J=6.8 Hz), 2.50(1H,t,J=2.4 Hz).

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.

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

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.

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

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.

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

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.

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

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.1-7.2(4H,m), 6.7-6.9(4H,m), 6.35(1H,t, J=71.7 Hz), 6.01(1H,br), 3.8-3.9(5H,m), 3.6-3.7(2H,m), 2.82(2H,t, J=6.8 Hz), 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

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).

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

Production Example 21

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).

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

Production Example 22

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).

1 H-NMR(CDCl 3 , 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=2.4 Hz), 4.52(2H,d,J=2.4 Hz), 3.86(3H,s), 3.6-3.7(2H,m), 2.84(2H,t,J=6.9 Hz), 2.63(1H,d,J=2.4 Hz), 2.51(1H,d,J=2.42 Hz).

Production Example 23

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).

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

Production Example 24

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).

1 H-NMR(CDCl 3 , 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=71.7 Hz), 6.02(1H,br), 5.51(1H,s), 3.84(3H,s), 3.6-3.7(2H,m), 2.81(2H,t, J=6.9 Hz), 2.34(3H,s).

Production Example 25

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).

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

Production Example 26

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).

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

Reference Production Example 1

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.0-7.2(4H,m), 6.72(1H,d,J=8.2 Hz), 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=6.9 Hz), 2.34(3H,s).

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.

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.

1 H-NMR(CDCl 3 , 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=6.9 Hz), 2.35(3H,s).

Reference Production Example 2

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.

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

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.

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 13.66(1H,d,J=11.34 Hz), 7.2-7.3(2H,m), 7.0-7.1(3H,m), 6.74(1H,d,J=8.1 Hz), 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=6.8 Hz).

Reference Production Example 3

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

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 6.99(1H,d,J=8.1 Hz), 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).

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.

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 13.61(1H,d,J=11.2 Hz), 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

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.

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

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.

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

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.

1 H-NMR(CDCl 3 , 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=6.7 Hz), 2.66(2H,t,J=6.8 Hz), 2.0-2.4(2H,br).

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.1-7.2(4H,m), 6.72(1H,d,J=8.2 Hz), 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=6.9 Hz), 2.34(3H,s).

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 13.61(1H,d,J=11.3 Hz), 7.2-7.5(5H,m), 7.04(1H,d, J=11.0 Hz), 6.97(1H,d,J=8.2 Hz), 6.7-6.9(3H,m), 6.66(1H,d,J=2.0 Hz), 6.59(1H,dd,J=8.3, 1.9 Hz), 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

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.

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

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.

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

Reference Production Example 6

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.2-7.5(7H,m), 7.0-7.1(2H,m), 6.73(1H,d, J=8.3 Hz), 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=6.8 Hz).

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.

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

Reference Production Example 7

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 13.6(1H,d,J=11.3 Hz), 6.9-7.2(5H,m), 6.80(1H,d), J=7.8 Hz), 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=6.9 Hz), 2.35(3H,s).

Reference Production Example 8

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 13.6(1H,d,J=11.3 Hz), 7.2-7.4(2H,m), 7.0-7.1(3H, m), 6.82(1H,d,J=6.7,1.7 Hz), 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=6.9 Hz).

Reference Production Example 9

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.

1 H-NMR(CDCl 3 , 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).

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.

1 H-NMR(CDCl 3 , 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=6.3 Hz).

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.3-7.5(5H,m), 6.9-7.1(4H,m), 6.72(1H,d,J=8.1 Hz), 6.62(1H,d,J=1.9 Hz), 6.42(1H,dd,J=2.0,8.1 Hz), 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=6.4 Hz), 2.33(3H,s), 1.04(3H,d,J=6.6 Hz).

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 13.65(1H,d,J=11.2 Hz), 7.2-7.5(5H,m), 6.9-7.2(5H, m), 6.76(1H,d,J=8.2 Hz), 6.63(1H,d,J=1.88 Hz), 6.52(1H,dd,J=8.1,1.9Hz), 5.28(2H,d, J=7.6 Hz), 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=6.5 Hz).

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.

1 H-NMR(CDCl 3 , 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=8.0,1.8 Hz), 6.30(1H,t,J=71.7 Hz), 5.79(1H,d,J=8.1 Hz), 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=6.6 Hz).

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.

1 H-NMR(CDCl 3 , TMS) δ(ppm): 7.1-7.2(4H,m), 6.6-6.9(4H,m), 6.37(1H,t, J=71.5 Hz), 5.79(1H,d,J=7.7 Hz), 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=6.5 Hz).

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

Compound given by formula [I]:

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

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

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

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

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

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

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

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.

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.

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

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

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

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

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

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]: wherein R1 represents a C1-C10 haloalkyl group, C2-C10 haloalkenyl group, C3-C10 haloalkynyl group, C3-C8 halocycloalkyl group or C3-C10 alkynyl group;R2 represents a hydrogen atom or C1-C3 alkyl group; X represents an oxygen atom or sulfur atom; Y represents an oxygen atom or sulfur atom; Ar represents a non heterocyclic, 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, 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, C1-C6 alkyl group, C1-C6 alkoxy group, trfluoromethyl group, amino group and nitro group; and Z1 and Z2 may represents C2-C6 alkylenedioxy group together.

2. An amide compound according to claim 1, wherein Ar is an aromatic hydrocarbyl 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, 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.

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.