α-Benzyldopamine and some related compounds: Synthesis and pharmacological screening

Abstract

Claisen reaction of 3,4-dimethoxyphenylacetonitrile with ethyl phenylacetate, the following stepwise hydrolysis and decarboxylation afforded the amide V 1-(3,4-dimethoxyphenyl)-3-phenylpropan-2-one (VI). Leuckart reaction resulted in the crude formamide derivative IIIb which was subjected to alkaline hydrolysis to the primary amine Ib on the one hand, and to reduction to the secondary amine IIb on the other. Demethylation with hydrobromic acid gave hydrobromides of 1-(3,4-dihydroxyphenyl)-3-phenyl-2-propylamine (title compound Ia) and its N-methyl derivative IIa. The alcohol VII, obtained by reduction of the ketone VI, was transformed by treatment with thionyl chloride to the chloro compound VIII which afforded by substitution reaction with 1-methylpiperazine the piperazine derivative IX. While the methoxylated amines Ib and IIb have mild stimulating and some antiarrhythmic effects, N-methyl-α-benzyldopamine (IIa) displayed a clear dopaminomimetic character.