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

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 (R 1 ) 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 (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.

Synthesis and preliminary biological evaluations of (+)-isocampholenic acid-derived amides

“…Following our previous successful applications of BPC as an activating agent for acids, i.e. for the formation of activated pentafluorophenyl esters for the peptide bond formation [18][19][20], 1 was treated with BPC in the presence of Et 3 N in anhydrous MeCN. The in situ formed reactive ester 11 was coupled with a variety of aliphatic amines 12a-k, thus furnishing the corresponding amides 13a-k in 59-91 % isolated yields.…”