Synthesis of 2-substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidin-4(3H)-ones

Abstract

KEYWORDS 2-Substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidin-4(3H)-ones were synthesized in three steps from itaconic acid derivatives via cyclization with primary amines followed by Masamune-Claisen condensation, and cyclization of the newly formed β-keto esters with amidines. Preparation and/or isolation of β-keto esters with polar N-substituents failed, but the corresponding final products were obtained in a different way. 6-(1-(3-Hydroxypropyl)-5oxopyrrolidin-3-yl)-2-phenylpyrimidin-4(3H)-one was obtained by hydrogenolytic odeprotection of its o-benzyl derivative. Depending on reaction conditions, further mesylation of 6-(1-(3-(benzyloxy)propyl)-5-oxopyrrolidin-3-yl)-2-phenylpyrimidin-4(3H)-one followed by treatment with pyrrolidine gave either the monoaminated-or the diaminated product. The structures of novel compounds were determined by NMR. Lactams Cyclization HeterocyclesMedicinal chemistry Nitrogen heterocycles Nucleophilic substitution