Collect. Czech. Chem. Commun. 1994, 59, 1126-1136

Potential Nootropic Agents: Synthesis of Some 1,4-Disubstituted 2-Oxopyrrolidines and Some Related Compounds

Vladimír Valentaa, Jiří Urbanb, Jan Taimra and Zdeněk Polívkaa

a Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3, Czech Republic
b J. Heyrovský Institute of Physical Chemistry, Academy of Sciences of the Czech Republic, 182 23 Prague 8, Czech Republic


4-(Aminomethyl)-1-benzyl-2-oxopyrrolidine (VI) was transformed by treatment with (4-benzhydrylpiperazin-1-yl)carbonyl chlorides IIIb - IIId and with (4-methylpiperazin-1-yl)carbonyl chloride (IIIa) to the carboxamides IVa - IVd. Heating of 1-(ethoxycarbonylmethyl)-2,4-dioxopyrrolidine (XIX) in acetonitrile in the presence of water afforded XVIIIa. Treatment with ammonia led to the diamide XVIIIc, while alkaline hydrolysis of XVIIIa gave the dicarboxylic acid XVIIIb. 4-(Aminomethyl)-1-(4-methylthiobenzyl)-2-oxopyrrolidine (XII) was prepared by the reaction of 4-(methylthio)benzylamine with itaconic acid and the following sequence of reactions starting from the obtained carboxylic acid VII including esterification, reduction and treatment the obtained alcohol IX with thionyl chloride, synthesis of phthalimido derivative XI and hydrazinolysis. Amine XII added to 4-chlorophenyl isocyanate formed XIII. The compounds prepared were tested for nootropic activity.