Collect. Czech. Chem. Commun. 1990, 55, 1297-1310

Potential neuroleptics of the orthopramide series; synthesis of heterocyclic 5-amino-2-methoxybenzamides and of some related compounds

Vladimír Valenta, Jiří Holubek, Emil Svátek, Oluše Matoušová, Jiřina Metyšová and Miroslav Protiva

Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3


2-Methoxy-5-nitrobenzoyl chloride was reacted with 2-(aminomethyl)-1-ethylpyrrolidine, 3-amino-1-ethylpiperidine, 4-amino-1-benzylpiperidine, 1-benzylpiperazine, and 1-amino-4-benzylpiperazine and gave the N-substituted 2-methoxy-5-nitrobenzamides VIa-VIe. Their reduction with hydrazine hydrate and Raney nickel in ethanol afforded the corresponding 5-amino-2-methoxybenzamides VIIa-VIIe. The amino amides VIIb and VIIc were transformed to methylamino compounds XIb and XIc via the 4-toluenesulfonamides VIIIb and VIIIc and the N-methyl-4-toluenesulfonamides Xb and Xc. The N-(1-benzyl-4-piperidinyl)amides VIc, VIIc and XIc were found to be mild neuroleptics having antiapomorphine, some cataleptic and some ataxic activity.