Collect. Czech. Chem. Commun. 1987, 52, 2095-2106

Potential neuroleptics of the orthopramide series; Synthesis of N-substituted 5-(aminosulfonyl)-2-methoxybenzamides

Vladimír Valenta and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


The mixed anhydride of 5-(aminosulfonyl)-2-methoxybenzoic acid (VII) and monoethyl carbonate reacted with benzylamine, 1-methylpiperazine, and 1-benzylpiperazine to give the 5-(aminosulfonyl)-2-methoxybenzamides II, IV, and V. Heating the ethyl ester X with 4-amino-1-methyl-piperidine resulted in the amide III. Reaction of 5-(chlorosulfonyl)-2-methoxybenzoyl chloride (XI) with 1-benzylpiperazine afforded 5-(4-benzylpiperazinosulfonyl)-2-methoxybenzoic acid 4-benzylpiperazide (VI). Compounds II-VI are analogues of the antidopaminergic and antiemetic agent sulpiride (I) but only benzylpiperazides V and VI showed indications of psychotropic activity of the neuroleptic type.