European Journal of Chemistry 2013, 4(1), 1-6 | doi: https://doi.org/10.5155/eurjchem.4.1.1-6.718 | Get rights and content






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


Uros Groselj (1) , Georg Dahmann (2) , Branko Stanovnik (3) , Jurij Svete (4,*)

(1) Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, SI-1000, Slovenia
(2) Medicinal Chemistry, Boehringer-Ingelheim Pharma GmbH & Co. KG, Biberach, D-88397, Germany
(3) Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, SI-1000, Slovenia
(4) Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, SI-1000, Slovenia
(*) Corresponding Author

Received: 19 Dec 2012 | Revised: 07 Jan 2013 | Accepted: 08 Jan 2013 | Published: 31 Mar 2013 | Issue Date: March 2013

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.

4_1_1_6

Keywords


Lactams; Cyclization; Heterocycles; Medicinal chemistry; Nitrogen heterocycles; Nucleophilic substitution

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DOI: 10.5155/eurjchem.4.1.1-6.718

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Funding information


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

Citations

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[1]. Zhaohua Wan, Dan Wang, Zixuan Yang, Heng Zhang, Shengchun Wang, Aiwen Lei
Electrochemical oxidative C(sp3)–H azolation of lactams under mild conditions
Green Chemistry  22(12), 3742, 2020
DOI: 10.1039/D0GC00687D
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How to cite


Groselj, U.; Dahmann, G.; Stanovnik, B.; Svete, J. Eur. J. Chem. 2013, 4(1), 1-6. doi:10.5155/eurjchem.4.1.1-6.718
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), 1-6. doi:10.5155/eurjchem.4.1.1-6.718
Groselj, U., Dahmann, G., Stanovnik, B., & Svete, J. (2013). Synthesis of 2-substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidin-4(3H)-ones. European Journal of Chemistry, 4(1), 1-6. doi:10.5155/eurjchem.4.1.1-6.718
Groselj, Uros, Georg Dahmann, Branko Stanovnik, & Jurij Svete. "Synthesis of 2-substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidin-4(3H)-ones." European Journal of Chemistry [Online], 4.1 (2013): 1-6. Web. 5 Dec. 2020
Groselj, Uros, Dahmann, Georg, Stanovnik, Branko, AND Svete, Jurij. "Synthesis of 2-substituted 6-(5-oxo-1-phenylpyrrolidin-3-yl)pyrimidin-4(3H)-ones" European Journal of Chemistry [Online], Volume 4 Number 1 (31 March 2013)

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DOI Link: https://doi.org/10.5155/eurjchem.4.1.1-6.718

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