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

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 (R-1) via addition of a primary alkylamine to methyl acrylate followed by a seven-step transformation into the 6-benzyl-7-oxo4,5,6,7-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-beta-alanine into a 6-unsubstituted benzyl ester as the key intermediate. The 6-alkyl group (R-1) 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.