Parallel Synthesis of 2-Substituted 6-(5-Oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxamides

Abstract

Abstract:A library of 24 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxamides 10{1,2; 1-12} was prepared by a parallel solution-phase approach. The synthesis comprises a five-step transformation of itaconic acid (11) into 1-methyl and 1-phenyl substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxylic acids 17{1,2} followed by parallel amidation of 17{1,2} with a series of 12 aliphatic amines 18{1-12} to afford the corresponding carboxamides 10 in good overall yields and in 80-100% purity.

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

“…Their identities were confirmed by 13 C NMR and HRMS. Spectral data for compounds novel compounds 9b, 10b, 6a-g, and 12-16 were in agreement with the data for closely related known compounds [16,17]. Structural assignment of 1-(3-hydroxypropyl)-4-(2-phenyl-6-(pyrrolidin-1-yl)pyrimidin-4-yl)pyrrolidin-2-one (15) was based on 1 H NMR data.…”

“…In the last decade, the synthesis of aminoethyl functionalized heterocycles has represented an important part of our research studies. Within this context, we have been so far focused on the synthesis of two types of 2-(heteroaryl) ethylamines: a) the open-chain analogues of histamine, 1, [10][11][12][13] and bicyclic conformationally constrained analogues of histamine, 2-4, [14][15][16] and b) 2-substituted 6-(5-oxo-1phenylpyrrolidin-3-yl)pyrimidine-5-carboxamides, 5, as 2aminoethyl-functionalized pyrimidines [17]. In continuation, we have focused our attention on 2-substituted 6-(5-oxo-1phenylpyrrolidin-3-yl)pyrimidin-4(3H)-ones, 6, as novel type of 2-aminoethyl-functionalized pyrimidines (Scheme 1).…”