Patent ES-346816-A1 (ES)
Title: 0,3-disubstituted pyrrolidines
IPC: C07D207/08
Filed: 1967-11-06
Abstract: Novel compounds I in which R is H, 1-8C alkyl, 1-8C alkoxy, CF 3 or halo R1 is CH 3 or H (at least one being H) n is 2, 3 or 4 A is O, NR7 (in which R7 is H, 1-8C alkyl, propionyl, 1-8C alkoxy, or carboalkoxy) or a single bond and Z is (a) an R4-substituted phenyl (in which R4 is H, 1-8C alkyl, 1-8C alkoxy, CF 3 , halo or di(1-8C alkyl)amino) or if A is a single bond the following groups (b)-CR2(R8)OH (in which R2 and R3 are H, 1-8C alkyl, phenyl-1-8C alkyl-, cycloalkyl, phenyl or substituted phenyl) (c) -OCONR5(R6) (in which R5 and R6 are H, 1-8C alkyl, or phenyl) (d) or (e) (in which Y is carbonyl or methylene) are prepared by reacting a compound II with a compound III in which X is halo or if n is 2 X may be dialkylamino and in which the oxo group may be ketalized. Intermediates isolated are 1 - benzyl - 3 - phenoxypyrrolidine fumarate 1 - benzyl - 3 - (m - trifluoromethylphenoxy)- pyrrolidine hydrochloride 1 - benzyl - 3 - (o - methoxyphenoxy) - pyrrolidine and its hydrochloride 3 - phenoxy pyrrolidine hydrochloride 3 - (m - trifluoromethylphenoxy)- pyrrolidine hydrochloride 3 - (o - bromophenoxy) - pyrrolidine 1 - benzyl - 3 - (o - hydroxybenzylamino) - pyrrolidine hydrochloride 1 - benzyl - 3 - (2 - hydroxy - 3 - methoxybenzylamino) - pyrrolidine 1 - benzyl - 3 - (2 - hydroxy - 4 - diethylaminobenzylamino) - pyrrolidine 4 - (1 - benzyl - 3 - pyrrolidinyl) - 4,5 - dihydro - 1,4 - benzoxazepin - 3 - (2H) - one hydrochloride 4 - (1 - benzyl - 3 - pyrrolidinyl) - 9 - methoxy - 4,5 - dihydro - 1,4 - benzoxazepin - 3 - (2H) - one 4 - (1 - benzyl - 3 - pyrrolidinyl) - 8 - diethylamino - 4,5 - dihydro - 1,4 - henzoxazepin - 3 - (2H) - one 4 - (3 - pyrrolidinyl) - 4,5 - dihydro - 1,4 - benzoxazepin - 3 - (2H) - one 4 - (3 - pyrrolidinyl) - 9 - methoxy - 4,5 - dihydro - 1,4 - benzoxazepin - 3 - (2H) - one 4 - (3 - pyrrolidinyl) - 8 - diethylamino - 4,5 - dihydro - 1,4 - benzoxazepin - 3 - (2H) - one 1 - benzyl - [alpha] - ethyl - [alpha] - phenyl - 3 - pyrrolidine - methanol 1 - benzyl - 4 - methyl - [alpha] - ethyl - [alpha] - phenyl - 3 - pyrrolidine - methanol 1 - benzyl - [alpha] - methyl - [alpha] - phenyl - 3 - pyrrolidine - methanol 1 - benzyl - [alpha] - methyl - [alpha] - (p - trifluoromethylphenyl) - 3 - pyrrolidine - methanol [alpha] - ethyl - [alpha] - phenyl - 3 - pyrrolidine - methanol [alpha] - methyl - [alpha] - phenyl - 3 - pyrrolidine - methanol: [alpha] - methyl - [alpha] - (p - trifluoromethylphenyl) - 3 - pyrrolidine - methanol [alpha] - benzyl - [alpha] - ethyl - 3 - pyrrolidine - methanol [alpha] - phenyl - 3 - pyrrolidine - methanol [alpha] - cyclohexyl - [alpha] - phenyl - 3 - pyrrolidine - methanol 1 - benzyl - 2 - oxo - [alpha],[alpha] - diphenyl - 3 - pyrrolidine - methanol 1 - benzyl - [alpha],[alpha] - diphenyl - 3 - pyrrolidine - methanol I - benzyl - 3 - (m - trifluoromethylphenyl) - 3 - pyrrolidinol hydrochloride 1 - benzyl - 3 - (p - diethylaminophenyl) - 3 - pyrrolidinol 1 - benzyl - 3 - (o - tolyl) - 3 - pyrrolidinol 3 - (m - trifluoromethylphenyl) - 3 - pyrrolidinol 3 - (p - diethylaminophenyl) - 3 - pyrrolidinol 3 - (o - tolyl - 3 - pyrrolidinol) 3 - (m - trifluoromethyl - phenyl) - pyrrolidino hydrochloride 3 - (p - diethylaminophenyl)- pyrrolidine 3 - (o - tolyl) - pyrrolidine 4,5 - dihydro - 4 - benzyl - 1,4 - benzoxazepin 3 - (2H) - one 4 - benzyl - 9 - methoxy - 4,5 - dihydro - 1,4 - benzoxazepin - 3 - (2H) - one 4 - benzyl - 8 - diethylamino - 4,5 - dihydro - 1,4 - benzoxazepin - 3 - (2H) - one 4 - benzyl - 2,3,4,5 - tetrahydro - 1,4 - benzoxazepine hydrochloride 4 - benzyl - 9 - methoxy - 2,3,4,5 - benzoxazepine 4 - benzyl - 8 - diethylamino - 2,3,4,5 - benzoxazepine 2,3,4,5 - tetrahydro - 1,4 - benzoxazepine hydrochloride 9 - methoxy- 2,3,4,5 - tetrahydro - 1,4 - benzoxazepine 8 - diethylamino - 2,3,4,5 - tetrahydro - 1,4 - benzoxazepine N - (1 - benzyl - 3 - pyrrolidinyl) - phthalimide 4 - trifluoromethyl - N - (1 - benzyl - 3 - pyrrolidinyl) - phthalimide 4,5 - dimethoxy - N - (1 - benzyl - 3 - pyrrolidinyl) - phthalimide 4 - methyl - N - (1 - benzyl - 3 - pyrrolidinyl) - phthalimide N - (1 - benzyl - 3 - pyrrolidinyl) - isoindoline dihydrochloride 4 - trifluoromethyl - N - (1 - benzyl - 3 - pyrrolidinyl) - isoindoline: 4,5 - dimethoxy - N - (1 - benzyl - 3 - pyrrolidinyl) - isoindoline 4 - methyl - N - (1 - henzyl - 3 - pyrrolidinyl) - isoindoline N - (3 - pyrrolidinyl) - isoindoline dihydrochloride N - (3 - pyrrolidinyl) - 4 - trifluoromethyl - isoindoline N - (3 - pyrrolidinyl) - 4,5 - dimethoxy - isoindoline N - (3 - pyrrolidinyl) - 4 - methyl - isoindoline 4 - (1 - benzyl - 3 - pyrrolidinyl) - 2,3,4,5 - tetrahydro - 1,4 - benzoxazepine difumarate 4 - (1 - benzyl - 3 - pyrrolidinyl) - 9 - methoxy - 2,3,4,5 - tetrahydro - 1,4 - benzoxazepine 4 - (1 - benzyl - 3 - pyrrolidinyl) - 8 - diethylamino - 2,3,4,5 - tetrahydro -1,4 - benzoxazepine 4 - (3 - pyrrolidinyl) - 2,3,4,5 - tetrahydro - 1,4 - benzoxazepine difumarate 4 - (3 - pyrrolidinyl) - 9 - methoxy - 2,3,4,5 - tetrahydro - 1,4 - benzoxazepine 4 - (3 - pyrrolidinyl) - 8 - diethylamino - 2,3,4,5 - tetrahydro - 1,4 - benzoxazepine 2 - (1 - benzyl - 3 - pyrrolidinyl) - benzimidazole 2 - (3 - pyrrolidinyl) - benzimidazole dihydrochloride 1 - benzyl - 3 - (2 - methoxyanilino) - pyrrolidine fumarate 3 - (2 - methoxyanilino) - pyrrolidine hexamate 3 - anilino - pyrrolidine 3 - anilino - aspartimide 1 - (3 - benzoylpropyl) - 3 - pyrrolidinol and 1 - [3 - (4 - fluorobenzoylpropyl)]- 3 - pyrrolidinol. Pharmaceutical compositions comprise a compound I in association with a suitable carrier, are administered orally or parenterally and are useful as analgesics and tranquilizers.