parallel synthesis of 2-substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxamides平行合成2-substituted 6 -(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidine-5-carboxamides.pdf

Molecules 2012, 17, 5363-5384; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Parallel Synthesis of 2-Substituted 6-(5-Oxo-1-phenylpyrrolidin- 3-yl)pyrimidine-5-carboxamides 1 1 1 1 2 Bojana Črček , Jernej Baškovč , Uroš Grošelj , Drago Kočar , Georg Dahmann , Branko Stanovnik 1 and Jurij Svete 1,* 1 Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, P.O. Box 537, 1000 Ljubljana, Slovenia 2 Boehringer Ingelheim Pharma GmbH Co. KG, Medicinal Chemistry, 88397 Biberach, Germany * Author to whom correspondence should be addressed; E-Mail: jurij.svete@fkkt.uni-lj.si; Tel.: +386-1-2419-254; Fax: +386-1-2419-360. Received: 20 March 2012; in revised form: 24 April 2012 / Accepted: 26 April 2012 / Published: 8 May 2012 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. Keywords: parallel synthesis; pyrimidines; 2-(heteroa