European Journal of Chemistry

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

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Published: Mar 31, 2013
DOI: https://doi.org/10.5155/eurjchem.4.1.1-6.718
Keywords:
Lactams, Cyclization, Heterocycles, Medicinal chemistry, Nitrogen heterocycles, Nucleophilic substitution
Section
Research Article
Issue
Vol. 4 No. 1 (2013): March 2013
Dates
Received 2012-12-19
Accepted 2013-01-08
Published 2013-03-31


Main Article Content

Uros Groselj
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, SI-1000, Slovenia
Georg Dahmann
Medicinal Chemistry, Boehringer-Ingelheim Pharma GmbH & Co. KG, Biberach, D-88397, Germany
Branko Stanovnik
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, SI-1000, Slovenia
Jurij Svete
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, SI-1000, Slovenia

Abstract

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)-5-oxopyrrolidin-3-yl)-2-phenylpyrimidin-4(3H)-one was obtained by hydrogenolytic o-deprotection 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.

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Groselj, U.; Dahmann, G.; Stanovnik, B.; Svete, J. Synthesis of 2-Substituted 6-(5-Oxo-1-Phenylpyrrolidin-3-yl)pyrimidin-4(3H)-Ones. Eur. J. Chem. 2013, 4, 1-6.

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Supporting Agencies

Boehringer-Ingelheim Pharma GmbH & Co. KG (Biberach, Germany) and Slovenian Research Agency (Ljubljana, Slovenia) (Grant No, P1-0179).
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