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

Klara Lombar; Uroš Grošelj; Georg Dahmann; Branko Stanovnik; Jurij Svete

doi:10.1055/s-0034-1379547

Synthesis, Table of Contents

Synthesis 2015; 47(04): 497-506
DOI: 10.1055/s-0034-1379547

paper

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

Klara Lombar

^aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia Fax: ??? Email: jurij.svete@fkkt.uni-lj.si

,

Uroš Grošelj

^aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia Fax: ??? Email: jurij.svete@fkkt.uni-lj.si

,

Georg Dahmann

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

,

Branko Stanovnik

^aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia Fax: ??? Email: jurij.svete@fkkt.uni-lj.si

,

Jurij Svete*

^aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia Fax: ??? Email: jurij.svete@fkkt.uni-lj.si

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Abstract

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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.

Key words

histamine analogues - pyrazolo[1,5-c]pyrimidines - parallel synthesis - cyclization - amidation

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References

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Supplementary Material

Supporting Information

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

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