Potential nootropic agents: Synthesis of some (2-oxo-1-pyrrolidinyl)acetamides and some related compounds

Abstract

Ethyl (2-oxo-1-pyrrolidinyl)acetate was transformed by ester exchange to the 2-dimethylaminoethyl ester VI which was converted to the choline iodide ester VII. The mixed anhydride of (2-oxo-1-pyrrolidinyl)acetic acid and monoethyl carbonate was reacted with ethyl aminoacetate to give the ester VIII which was transformed on the one hand to the amide IX, and to the 2-dimethylaminoethyl ester X on the other. Reaction of the latter with methyl iodide afforded a further choline iodide ester XI. Reactions of (2-oxo-1-pyrrolidinyl)acetyl chloride with 4-chloroaniline and 3-aminopyridine gave the amides XII and XIV. The anilide XIII was obtained from 2-(2-oxo-1-pyrrolidinyl)butyric acid and 4-chloroaniline by means of dicyclohexylcarbodiimide. The benzo analogue (XV) of piracetam (I) was synthesized from oxindole via the ester XVI. The anilide XII (V⁄FB-16 536) was found to potentiate significantly the anticonvulsant effect of diazepam in mice, to prolong the survival time of mice under conditions of nitrogen anoxia, and to prolong significantly the duration of the "gasping reflex" in mice.