Synthesis of several 4-hydroxy-3,5-dimethoxybenzamides, their O-substituted derivatives and some related compounds as potential neurotropic agents

Abstract

Reactions of 4-benzyloxy-3,5-dimethoxybenzoyl chloride with pyrrolidine, piperidine, morpholine and 1-methylpiperazine gave the amides IIIa-IIId which were debenzylated by catalytic hydrogenation on palladium. The 4-hydroxy-3,5-dimethoxybenzamides IVa-IVc were then treated with sodium hydride and 2-dimethylaminoethyl chloride to give the O-(2-dimethylaminoethyl)amides Va-Vc. The 3,4,5-trimethoxybenzamide IX was prepared as a homologue of the antiemetic agent "trimethobenzamide" (II) and reduced to the benzylaniline derivative X. The substituted nicotinamide XI was obtained from nicotinoyl chloride and 4-(2-diethylaminoethoxy)aniline. Out of the compounds prepared the amides IIId and Vc had some anticonvulsant activity, the piperazide IVd revealed a significant α-adrenolytic effect and the amino ether X reduced the blood pressure of normotensive rats.