Vinylation of α-Aminoazoles with Triethylamine: A General Strategy to Construct Azolo[1,5-<i>a</i>]pyrimidines with a Nonsubstituted Ethylidene Fragment
Qinghe Gao, Zhenhua Sun, Qinfei Xia, Ruonan Li, Wenlong Wang, Siwei Ma, Yixin Chai, Manman Wu, Wei Hu, Péter Ábrányi‐Balogh, György M. Keserű, Xinya Han
Abstract
A new general synthesis of pharmaceutically important azolo[1,5-a]pyrimidines starting from widely available 3(5)-aminoazoles, aldehydes, and triethylamine is developed. The key is to enable the vinylation reaction that allows the in situ generation of elusive acyclic enamines and the subsequent annulation reaction to occur. This direct and practical strategy is capable of constructing a range of 5,6-unsubstituted pyrazolo[1,5-a]pyrimidines and [1,2,4]triazolo[1,5-a]pyrimidines. More importantly, this protocol provides a concise synthetic route to prepare the clinically used zaleplon.
Topics & Concepts
TriethylamineAnnulationChemistryCombinatorial chemistryReaction conditionsStereochemistryOrganic chemistryCatalysisSynthesis and Reactivity of HeterocyclesSynthesis and Biological EvaluationSynthesis and Catalytic Reactions