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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References

[1]. Patrick, G. L. An Introduction to Medicinal Chemistry; 3rd edition, Oxford University Press, 2005.

[2]. Kazuta, Y.; Hirano, K.; Natsume, K.; Yamada, S.; Kimura, R.; Matsumoto, S. I.; Furuichi, K.; Matsuda, A.; Shuto, S. J. Med. Chem. 2003, 46, 1980-1989.
http://dx.doi.org/10.1021/jm020415q
PMid:12723960

[3]. Paillet-Loilier, M.; Fabis, F.; Lepailleur, A.; Bureau, R.; Butt-Gueulle, S.; Dauphin, F.; Lesnard, A.; Delarue, C.; Vaudryb, H.; Rault, S. Bioorg. Med. Chem. Lett. 2007, 17, 3018-3022.
http://dx.doi.org/10.1016/j.bmcl.2007.03.054
PMid:17419056

[4]. Pullagurla, M.; Dukat, M.; Roth, B. L.; Setola, V.; Glennon, R. A. Med. Chem. Res. 2005, 14, 1-18.
http://dx.doi.org/10.1007/s00044-004-0121-8

[5]. Dolle, R. E. Solid-phase Synthesis of Heterocyclic Systems (Heterocycles Containing One Heteroatom). In Handbook of Combinatorial Chemistry. Drugs, Catalysts, Materials, Vol. 2, Nicolaou, K. C., Hanko, R., Hartwig, W., Eds., Wiley-VCH Verlag GmbH, 2002, pp. 643-684.

[6]. Pernerstorfer, J. Molecular Design and Combinatorial Compound Libraries. In Handbook of Combinatorial Chemistry. Drugs, Catalysts, Materials, Vol. 2, Nicolaou, K. C.; Hanko, R.; Hartwig, W. Eds., Wiley-VCH Verlag GmbH, 2002, pp. 725-742.

[7]. Dolle, R. E.; Le Bourdonnec, B.; Morales, G. A.; Moriarty, K. J.; Salvino, J. M. J. Comb. Chem. 2008, 10, 753-802.
http://dx.doi.org/10.1021/cc800119z
PMid:18991466

[8]. Dolle, R. E.; Le Bourdonnec, B.; Goodman, A. J.; Morales, G. A.; Thomas, C. J.; Zhang, W. J. Comb. Chem. 2009, 11, 739-790.
http://dx.doi.org/10.1021/cc9000828
PMid:19715292

[9]. Dolle, R. E.; Le Bourdonnec, B.; Worm, K.; Morales, G. A.; Thomas, C. J.; Zhang, W. J. Comb. Chem. 2010, 12, 765-806.
http://dx.doi.org/10.1021/cc100128w
PMid:20923157

[10]. Kralj, D.; Grošelj, U.; Meden, A.; Dahmann, G.; Stanovnik, B.; Svete, J. Tetrahedron 2007, 63, 11213-11222.
http://dx.doi.org/10.1016/j.tet.2007.07.052

[11]. Kralj, D.; Novak, A.; Dahmann, G.; Grošelj, U.; Meden, A.; Svete, J. J. Comb. Chem. 2008, 10, 664-670.
http://dx.doi.org/10.1021/cc8000794
PMid:18630970

[12]. Kralj, D.; Friedrich, M.; Grošelj, U.; Kiraly-Potpara, S.; Meden, A.; Wagger, J.; Dahmann, G.; Stanovnik, B.; Svete, J. Tetrahedron 2009, 65, 7151-7162.
http://dx.doi.org/10.1016/j.tet.2009.06.021

[13]. Grošelj, U.; Kralj, D.; Wagger, J.; Dahmann, G.; Stanovnik, B.; Svete, J. Arkivoc 2012, 3, 49-65.

[14]. Žerovnik, D.; Grošelj, U.; Kralj, D.; Malavašič, Č.; Bezenšek, J.; Dahmann, G.; Stare, K.; Meden, A.; Stanovnik, B.; Svete, J. Synthesis 2010, 3363-3373.

[15]. Janjić, M.; Prebil, R.; Grošelj, U.; Kralj, D.; Malavašič, Č.; Golobič, A.; Stare, K.; Dahmann, G.; Stanovnik, B.; Svete, J. Helv. Chim. Acta 2011, 94, 1703-1717.
http://dx.doi.org/10.1002/hlca.201100055

[16]. Perdih, P.; Baškovč, J.; Dahmann, G.; Grošelj, U.; Kočar, D.; Novak, A.; Stanovnik, B.; Svete, J. Synthesis 2011, 2822-2832.

[17]. Črček, B.; Baškovč, J.; Grošelj, U.; Kočar, D.; Dahmann, G.; Stanovnik, B.; Svete, J. Molecules 2012, 17, 5363-5384.
http://dx.doi.org/10.3390/molecules17055363
PMid:22569416

[18]. Paytash, P. L.; Sparrow, E.; Gathe, J. C. J. Am. Chem. Soc. 1950, 72, 1415-1416.
http://dx.doi.org/10.1021/ja01159a520

[19]. Hu, X. E.; Cassady, J. M. Syn. Commun. 1995, 25, 907-913.
http://dx.doi.org/10.1080/00397919508013428

[20]. Felluga, F.; Pitacco, G.; Prodan, M.; Pricl, S.; Visintin, M.; Valentin, E. Tetrahedron: Asym. 2001, 12, 3241-3249.
http://dx.doi.org/10.1016/S0957-4166(01)00523-7

Supporting Agencies

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