Synthesis 2015; 47(04): 497-506
DOI: 10.1055/s-0034-1379547
paper
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 6-Alkyl-7-oxo-4,5,6,7-tetrahydropyrazolo[1,5-c]pyri­midine-3-carboxamides

Klara Lombar
a   Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia   Fax: ???   Email: jurij.svete@fkkt.uni-lj.si
,
Uroš Grošelj
a   Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia   Fax: ???   Email: jurij.svete@fkkt.uni-lj.si
,
Georg Dahmann
b   Boehringer Ingelheim Pharma GmbH & Co. KG, Medicinal Chemistry, 88397 Biberach, Germany
,
Branko Stanovnik
a   Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia   Fax: ???   Email: jurij.svete@fkkt.uni-lj.si
,
Jurij Svete*
a   Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia   Fax: ???   Email: jurij.svete@fkkt.uni-lj.si
› Author Affiliations
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Publication History

Received: 26 September 2014

Accepted after revision: 29 October 2014

Publication Date:
24 November 2014 (online)


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Abstract

Two variants of the synthesis of 6-alkyl-7-oxo-4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidine-3-carboxamides have been developed. The first pathway comprises nine steps starting with the introduction of the 6-alkyl group (R1) via addition of a primary alkylamine to methyl acrylate followed by a seven-step transformation into the 6-benzyl-7-oxo-4,5,6,7-tetrahydropyrazolo[1,5-c]pyrimidine-3-carboxylic acid, which is then amidated into title compounds. The other variation is based on an analogous four-step transformation of Boc-β-alanine into a 6-unsubstituted benzyl ester as the key intermediate. The 6-alkyl group (R1) is then introduced by N-alkylation with alkyl halides, followed by O-debenzylation to give the carboxylic acids, and amidation. A library of 18 title carboxamides was prepared in very good yields.

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