Patent GB-1202747-A (GB)
Title: 0,3-disubstituted pyrrolidines
Inventor: LUNSFORD CARL DALTON
IPC: C07D207/12
Filed: 1967-11-06
Abstract: 1,202,747. Substituted pyrrolidines. A. H. ROBINS CO. Inc. 6 Nov., 1967 [7 Nov., 1966], No. 50259/67. Heading C2C. Novel compounds I in which R is H, 1-8C alkyl, 1-8C alkoxy, CF 3  or halo; R<SP>1</SP> is CH 3  or H (at least one being H); n is 2, 3 or 4; A is O, NR<SP>7</SP> (in which R<SP>7</SP> is H, 1-8C alkyl, propionyl, 1-8C alkoxy, or carboalkoxy) or a single bond and Z is (a) an R<SP>4</SP>-substituted phenyl (in which R<SP>4</SP> 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)-CR<SP>2</SP>(R<SP>8</SP>)OH (in which R<SP>2</SP> and R<SP>3</SP> are H, 1-8C alkyl, phenyl-1-8C alkyl-, cycloalkyl, phenyl or substituted phenyl); (c) -OCONR<SP>5</SP>(R<SP>6</SP>) (in which R<SP>5</SP> and R<SP>6</SP> 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 - α - ethyl - α - phenyl - 3 - pyrrolidine - methanol; 1 - benzyl - 4 - methyl - α - ethyl - α - phenyl - 3 - pyrrolidine - methanol; 1 - benzyl - α - methyl - α - phenyl - 3 - pyrrolidine - methanol; 1 - benzyl - α - methyl - α - (p - trifluoromethylphenyl) - 3 - pyrrolidine - methanol; α - ethyl - α - phenyl - 3 - pyrrolidine - methanol ; α - methyl - α - phenyl - 3 - pyrrolidine - methanol: α - methyl - α - (p - trifluoromethylphenyl) - 3 - pyrrolidine - methanol; α - benzyl - α - ethyl - 3 - pyrrolidine - methanol; α - phenyl - 3 - pyrrolidine - methanol; α - cyclohexyl - α - phenyl - 3 - pyrrolidine - methanol; 1 - benzyl - 2 - oxo - α,α - diphenyl - 3 - pyrrolidine - methanol ; 1 - benzyl - α,α - 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.