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Synthesis 2013; 45(5): 639-650
DOI: 10.1055/s-0032-1318107
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© Georg Thieme Verlag Stuttgart · New York

Synthesis of Tetrahydropyrazolo[1,5-c]pyrimidine-2,7(1H,3H)-diones

Uroš Grošelj*
a   Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, P. O. Box 537, 1000 Ljubljana, Slovenia   Fax: +386(1)2419220   Email: jurij.svete@fkkt.uni-lj.si
,
Anja Podlogar
a   Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, P. O. Box 537, 1000 Ljubljana, Slovenia   Fax: +386(1)2419220   Email: jurij.svete@fkkt.uni-lj.si
,
Ana Novak
a   Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, P. O. Box 537, 1000 Ljubljana, Slovenia   Fax: +386(1)2419220   Email: jurij.svete@fkkt.uni-lj.si
,
Georg Dahmann
b   Boehringer Ingelheim Pharma GmbH & Co. KG, Medicinal Chemistry, 88397 Biberach, Germany
,
Amalija Golobič
a   Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, P. O. Box 537, 1000 Ljubljana, Slovenia   Fax: +386(1)2419220   Email: jurij.svete@fkkt.uni-lj.si
,
Branko Stanovnik
a   Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, P. O. Box 537, 1000 Ljubljana, Slovenia   Fax: +386(1)2419220   Email: jurij.svete@fkkt.uni-lj.si
,
Jurij Svete*
a   Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, P. O. Box 537, 1000 Ljubljana, Slovenia   Fax: +386(1)2419220   Email: jurij.svete@fkkt.uni-lj.si
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Further Information

Publication History

Received: 22 November 2012

Accepted after revision: 27 December 2012

Publication Date:
24 January 2013 (online)

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Dedicated to Professor Emeritus Volker Jäger, Institut für Organische Chemie, Universität Stuttgart, on the occasion of his 70th birthday.

Abstract

A series of tetrahydropyrazolo[1,5-c]pyrimidine-2,7(1H,3H)-diones 3a–h as the first representatives of the so far unexplored saturated heterocyclic system have been synthesized, formally in 12 steps from methyl acrylate (4). The synthesis comprises a four-step preparation of methyl N-Cbz-5-alkylamino-3-oxopentanoates 9a–c, their three-step transformation into 5-{2-[(alkyl)(benzyloxycarbonyl)amino]ethyl}pyrazolidin-3-ones 12a–c, three-step selective alkylation of the amidic N-2 to give 2-alkyl-5-{2-[(alkyl)(benzyloxycarbonyl)amino]ethyl}pyrazolidin-3-ones 16b–h, followed by hydrogenolytic Cbz-deprotection and subsequent cyclization of the intermediate 1,4-diamine with CDI to furnish the title compounds 3. Most of the synthetic steps were performed as a one-pot transformation.

Key words

pyrazolo[1,5-c]pyrimidines - cyclization - saturated heterocycles - 3-pyrazolidinones

Supporting Information

    for this article containing copies of 1H and 13C spectra of compounds 3, 8–13, 15, and 16 is available online at http://www.thieme-connect.com/ejournals/toc/synthesis.
  • Supporting Information
 

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