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

Uroš Grošelj; Anja Podlogar; Ana Novak; Georg Dahmann; Amalija Golobič; Branko Stanovnik; Jurij Svete

doi:10.1055/s-0032-1318107

Synthesis, Table of Contents

Synthesis 2013; 45(5): 639-650
DOI: 10.1055/s-0032-1318107

paper

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

Uroš Grošelj*

^aFaculty 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

^aFaculty 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

^aFaculty 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

^bBoehringer Ingelheim Pharma GmbH & Co. KG, Medicinal Chemistry, 88397 Biberach, Germany

,

Amalija Golobič

^aFaculty 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

^aFaculty 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*

^aFaculty 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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Abstract

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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

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References

References

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15 Structural and other crystallographic data have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 910129, CCDC 910351, and CCDC 910352 for compounds 3h, 3a, and 3c, respectively. A copy of the data can be obtained, free of charge, by applying to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax: +44(0)1223336033 or e-mail: deposit@ccdc.cam.ac.uk).

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