Patent ES-349061-A1 (ES)
Title: Improvements in or relating to naphthalene derivatives
IPC: C07C49/697
Filed: 1968-01-09
Abstract: The invention comprises naphthylacetic acids of the formul[mu] wherein one of R1 and R2 is H and the other is F 2 CH-, F or Cl or R1 and R2 taken together are alkylidene halomethylene, or ethylene R3 is CF 3 , hydrolysable ester, F 2 CHO-, alkoxymethoxy, 41 - alkoxytetrahydropyran- 41 - yloxy, tetrahydrofuran - 21 - yloxy, tetrahydropyran - 21- yloxy, or thioether R4 is cycloalkyl, HOCH 2 -, alkoxymethyl, CF 3 , vinyl, ethynyl, hydrolysable ester, alkoxymethyloxy, alkylthiomethylthio, F 2 CHO-, alkoxymethylthio, alkylthiomethyloxy, F2- CHSHCO-, HOOC-, alkoxycarbonyl, CH 3 CO-, CN-, or aryl each of R5 (at positions 4, 7 or 8) and R6 (at positions 1, 4, 7 or 8) is alkyl, CF 3 , F, Cl, OH, hydrolysable ester, oxyether, or thioether provided that R5 (when at position 7) is other than alkyl R7 is alkyl, cycloalkyl, HOCH 2 -, alkoxymethyl, CF 3 , vinyl, ethynyl, F, Cl, OH, hydrolysable ester, oxyether, thioether, HCO, -COOH, alkoxycarbonyl, CH 3 CO-, CN, or aryl each of R8 and R9 (at positions 1, 4, 7 or 8) is alkyl, F, Cl, OH, hydrolysable ester, oxyether, or thioether provided that when one of R8 and R9 is OH, oxyether or thioether, the other is the identical group or alkyl, F, Cl, or hydrolysable ester one of R10 and R11 is H, the other being CH 3 , CH 3 CH 2 , F 2 CH-, F or Cl or R10 and R11 taken together are alkylidene, halomethylene, or ethylene provided that when one of R10 or R11 is CH 3 or CH 3 CH 2 -, R6 (when at position 1 or 7) is other than alkyl each of R12 and R15 (at positions 1 or 4) is OH, oxyether or thioether each of R13 (at positions 1 or 4) and R14 is alkoxy or alkylthio provided that when R12 or R15 is alkoxy or alkylthio, R13 or R14, respectively, is a different alkoxy or alkylthio group one of R16 and R17 is H, the other being H, CH 3 , CH 3 CH 2 , F 2 CH-, F or Cl or R16 and R17 taken together are alkylidene, halomethylene, or ethylene R20 (at position 1, 7 or 8) is alkyl, F, Cl, OH, hydrolysable ester, oxyether, or thioether provided that when one of R8 and R20 is OH, oxyether or thioether, the other is the identical group or alkyl, F, Cl, or hydrolysable ester R19 (at position 1, 7 or 8) is alkyl, CF 3 , F, Cl, OH, hydrolysable ester, oxyether, or thioether provided that when R18 and R17 are H or one of R16 and R17 is CH 3 or C 2 H 5 , R19 (when at position 1) is other than OH and R21 is H, alkyl, cycloalkyl, CF 3 , F, Cl, OH, hydrolysable ester, oxyether, thioether, or aryl provided that at least one of R16, R17 and R21 is other than H provided that when one of R18 or R17 is CH 3 or CH 3 CH 2 , R21 is other than H, and the corresponding amides, esters, hydroxamic acids and pharmaceutically acceptable addition salts thereof. The above compounds and naphthylacetic acids, and amides, esters, hydroxamic acids and pharmaceutically acceptable addition salts of the formul[mu] wherein R18 is H, alkyl, cycloalkyl, CF 3 , HOCH 2 -, alkoxymethyl, vinyl, ethynyl, F, Cl, OH, hydrolysable ester, oxyether, thioether, HCO-, HOOC-, alkoxycarbonyl, CH 3 CO, CN or aryl are prepared by standard methods. The following intermediates are prepared: 4 - (31,41 - dimethoxyphenyl) - 4 - oxobutanoic acid, 4 - (31,41 - dimethoxyphenyl) butanoic acid, 4 - (31,41 - dimethoxyphenyl) butanoic acid chloride, 6,7 - dimethoxy - 1 - tetralone, 6,7 - dimethoxytetralin, 2,3 - dimethoxynaphthalene, 5 - fluoro - 7 - methyl - 1 - tetralone, 5 - methyl - 7 - fluoro - 1 - tetralone, 1- methyl - 3 - fluoronaphthalene, 1 - fluoro - 3 - methylnaphthalene, 2 - (11 - hydroxycyclobutyl)naphthalene, 2 - ([alpha] - bromoethyl)- naphthalene, 2 - ([alpha],# - dibromoethyl)naphthalene, 2 - acetylnaphthalene, 2 - ([alpha] - acetoxyethyl)naphthalene, 2 - ([alpha] - hydroxyethyl)- naphthalene, 2 - carboxynaphthalene, 2- hydroxymethylnapht halene, 2 - formylnaphthalene, 2 - cyanonaphthalene, 2 - naphthaldehyde oxime, 2 - methoxy - 4 - (31- carboxy- 11 - oxopropyl)toluene, 2 - methoxy - 5 - (31- carboxy - 11 - oxopropyl)toluene, 6 - methyl- 7 - methoxy - 1 - tetralone, 7 - methyl - 6 - methoxy - 1 - tetralone, 6 - methyl - 7 - methoxy- 1 - hydroxy - 1,2,3,4 - tetrahydronaphthalene, 6 - methoxy - 7 - methyl - 1 - hydroxy - 1,2,3,4- tetrahydronaphthalene, 2 - methyl - 3 - methoxynaphthalene, 5 - ethoxy - 7 - chloro - 1 - tetralone, 5 - chloro - 7 - ethoxy - 1 - tetralone, 1 - ethoxy - 31 - chloronaphthalene, 1 - chloro- 3 - ethoxynaphthalene, 5 - ethoxy - 7 - chlorotetralin, 6 - chloro - 8 - ethoxy - 1 - tetralone, 7 - fluoro - 1 - tetralone, 2- fluoronaphthalene, 7 - methoxy - 1 - tetralone, 7 - isopropyl- 1 - tetralone, 7 - methylthio - 1 - tetralone, 6- chloro - 7 - methylthio - 1 - tetralone, 6 - fluoro- 7 - methyl - 1 - tetralone, 6 - methoxy - 7 - fluoro- 1 - tetralone, 6,8 - dimethyl - 1 - tetralone, 6- methylthio - 8 - cyclopropyl - 1 - tetralone, 6 - methyl - 8 - isopropyl - 1 - tetralone, 2- methylthio - 3 - chloronaphthalene, 2 - methyl- 3 - fluoronaphthalene, 2 - fluoro - 3 - methoxynaphthalene, 1 - methylthio - 3 - cyclopropylnaphthalene, 2 - p - fluorophenyl - 3,4 - dihydronaphthalene, 2 - p - fluorophenylnaphthalene, 2 - p - chlorophenylnaphthalene, 2- acetyl - 6 - methoxy - naphthalene, 6 - methoxy- 2 - naphthylthioacetmorpholide, 6 - methoxy- 2 - ethoxycarbonyl - 1 - tetralone, 6 - methoxy- 2 - ethoxycarbonyl - 2 - (ethoxycarbonylmethyl) - 1 - tetralone, 6 - methoxy - 2 - (carboxymethyl) - 1 - tetralone, 6 - methoxy- 1 - hydroxy - 1,2,3,4 - tetrahydro - 2 - naphthylacetic acid, 6 - methoxy - 1,2,3,4 - tetrahydro - 2 - naphthylacetic acid, methyl- 6 - methoxy - 1,2,3,4 - tetrahydro - 2 - naphthylacetate, methyl 6 - methoxy - 1 - hydroxy- 1,2,3,4 - tetrahydro - 2 - naphthylacetate, methyl 1,6 - dimethoxy - 1,2,3,4 - tetrahydro- 2 - naphthylacetate, 6 - methoxy - 2 - (methoxycarbonylmethylene) - 1 - tetralone, methyl 6 - methoxy - 1 - fluoro - 1,2,3,4 - tetrahydro- 2 - naphthylacetate, methyl 6 - methoxy- 1,2 - dihydro - 2 - naphthylacetate, dimethyl 3 - (p - chlorobenzoyl)glutarate, dimethyl 3- (p - chlorobenzyl)glutarate, 3 - (p - chlorobenzyl)glutaric acid, 7 - chloro - 3 - (carboxymethyl) - 1 - tetralone, 7 - chloro - 3 - (methoxycarbonylmethyl) - 1 - tetralone, 3 - methoxycarbonylmethyl) - 1 - tetralone, 7 - methyl- 3 - (methoxycarbonylmethyl) - 1 - tetralone, 7 - ethyl - 3 - (methoxycarbonylmethyl)- 1 - tetralone, 7 - isopropyl - 3 - (methoxycarbonylmethyl) - 1 - tetralone, 7 - methylthio- 3 - (methoxycarbonylmethyl) - 1 - tetralone, 7 - fluoro - 3 - (methoxycarbonylmethyl)- 1 - tetralone, 7 - methoxy - 3 - (methoxycarbonylmethyl) - 1 - tetralone, 7 - ethoxy - 3 - (methoxycarbonylmethyl) - 1 - tetralone, 7- ethylthio - 3 - (methoxycarbonylmethyl)- 1 - tetralone, methyl 6 - fluoro - 4 - hydroxy- 1,2,3,4 - tetrahydro - 2 - naphthylacetate, methyl 6 - methyl - 4 - hydroxy - 1,2,3,4 - tetrahydro - 2 - naphthylacetate, methyl p - (31- carboxy - 11 - oxopropyl)phenylacetate, methyl p - (31 - carboxypropyl)phenylacetate, methylp - (31 - chlorocarbonylpropyl)phenylacetate, 7 - (methoxycarbonylmethyl) - 1 - tetralone, ethyl 6 - methoxy - 2 - naphthyl - [alpha],[alpha] - hydroxymethyleneacetate, ethyl 6 - methoxy - 2 - naphthyl - [alpha] - formyl - [alpha] - chloroacetate, ethyl 6 - methoxy - 2 - naphthyl - [alpha] - carboxy- [alpha] - chloroacetate, methyl 6 - methyl - 2 - naphthyl - [alpha] - hydroxyacetate, methyl 6 - methyl- 2 - naphthyl - [alpha] - oxoacetate, difluoromethylene triphenyl phosphorane, chlorofluoromethylene triphenyl phosphorane, methyl 6-fluoro-2-naphthyl - [alpha] - hydroxymethylacetate, diethyl 6- methoxy - 2 - naphthylmalonate, diethyl 6- methoxy - 2 - naphthyl - [alpha] - difluoromethylmalonate, 6 - methoxy - 2 - naphthyl - [alpha] - difluoromalonic acid, diethyl 6 - methoxy- 2 - naphthyl - [alpha] - methylmalonate, methyl 6 - trichloromethyl - 2 - naphthyl - [alpha] - methyl acetate, methyl 6 - ([alpha] - bromoethyl) - 2 - naphthyl - [alpha] - methylacetate, methyl 6 - ([alpha] - acetoxyethyl) - 2 - naphthyl - [alpha] - methylacetate, methyl 6 - ([alpha] - hydroxyethyl) - 2 - naphthyl- [alpha] - methylacetate, the oxime of 6 - formyl- 2 - naphthyl - [alpha] - methylacetic, 1 - ethoxycarbonylethylidene triphenyl phosphorane, 2,2 - (11 - carbethoxyeth - 11,11 - ylidene)- 6 - methoxytetralin, and methyl 6 - mercapto- 2-naphthyl-[alpha]-methylacetate.