Improvements in or relating to n-phenethyl-2-phenylcyclopropylamine derivatives

摘要

The invention comprises N-phenethyl-2-phenylcyclopropylamine derivatives of the general formula (wherein R1 and R2 are phenyl, chlorophenyl, fluorophenyl, trifluoromethylphenyl, lower alkoxyphenyl, lower alkylphenyl, dichlorophenyl, di-lower alkylphenyl, di-lower alkoxyphenyl or methylenedioxyphenyl, R3 is hydrogen, lower alkyl or hydroxyethyl, and R4 is lower alkyl) and non-toxic, pharmaceutically acceptable, acid addition salts thereof, and their preparation by the processes of the examples which may be summarized by the following reaction scheme:- (wherein R3 is lower alkyl or hydroxyethyl), optionally followed by salt formation. The "lower alkyl" and "lower alkoxy" groups are defined as those containing from 1 to 4 carbon atoms. These compounds may be the cis- and transisomers and the resolved d-, l-, d1- and l1-isomers prepared by using the appropriate starting material, followed by resolution), or mixtures of cis-trans, dl- and d1l1-isomers. The compounds are anorexigenic agents, anti-depressants, ataractics and monoamine oxidase inhibitors. The cis-, trans- and cis-trans-2-phenylcyclopropylamine starting materials may be prepared by the following process: The acid may be converted to the azide via the acid chloride. Alternatively, the acid may be converted to the amine via the methyl ester, hydrazide, azide and methyl urethane. The separation of the cis- and transisomers may be effected at the ethyl ester or acid stage. The benzyl alkyl ketone starting materials may be prepared by reacting the appropriate phenylacetic acid with an excess of the appropriate acid anhydride in the presence of a basic catalyst. 4-Trifluoromethylphenylacetic acid is prepared from 4-bromobenzotrifluoride via 4- trifluoromethylbenzaldehyde, 4- trifluoromethylbenzyl alcohol, 4-trifluoromethylbenzyl bromide and 4-trifluoromethylbenzyl cyanide. d-cis, l-cis, d-trans- and l-trans-2-Phenylcyclopropylamine are prepared from dl-cis-and dl-trans-2-phenylcyclopropylamine via the tartrates.