Stepwise synthesis of 2,6-difunctionalized ethyl pyrazolo[1,5-a]pyrimidine-3-carboxylate via site-selective
Chaima Messaoudi1,2, Badr Jismy1, Johan Jacquemin3
1Laboratoire de Physico-Chimie des Matériaux et des Electrolytes pour l'Energie (PCM2E), EA 6299. Université de Tours, Faculté des Sciences et Techniques, Avenue Monge Faculté des Sciences, Parc de Grandmont, 37200 Tours, France. badr.jismy@hotmail.com.
Abstract:
A variety of novel disubstituted 2-(alknyl, aryl and arylamine)-6-alkynylpyrazolo[1,5-a]pyrimidine derivatives was prepared via sequential site-selective cross-coupling reactions from 2,6-dibromopyrazolo[1,5-a]pyrimidine 3. The regio-controlled Sonogashira-type coupling of 3 with a wide range of terminal alkynes proceeded smoothly with excellent selectivity in favor of the C6-position through careful adjustment of the coupling conditions, followed by the subsequent introduction of alkynyl, aryl or arylamine groups at the C2-position via the Sonogashira, Suzuki-Miyaura and Buchwald-Hartwig coupling reactions, respectively. These promising results allow for further use and diversification of the chemically and biologically interesting pyrazolo[1,5-a]pyrimidine scaffold. In addition, computational studies were conducted to provide explanations for the origin of regioselectivity.
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