School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, P. R. China.
School of Chemistry and Chemical Engineering, Anhui University of Technology, Maanshan, Anhui 243002, P. R. China.
Org Lett. 2021 Apr 2;23(7):2664-2669. doi: 10.1021/acs.orglett.1c00571. Epub 2021 Mar 18.
A new general synthesis of pharmaceutically important azolo[1,5-]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-]pyrimidines and [1,2,4]triazolo[1,5-]pyrimidines. More importantly, this protocol provides a concise synthetic route to prepare the clinically used zaleplon.
从广泛存在的 3(5)-氨基唑、醛和三乙胺出发，开发了一种新的具有重要药用价值的氮杂[1,5-]嘧啶的通用合成方法。关键是要使乙烯基化反应能够进行，从而使难以得到的非环烯胺原位生成，并随后发生环化反应。这种直接实用的策略能够构建一系列 5,6-未取代的吡唑并[1,5-]嘧啶和[1,2,4]三唑并[1,5-]嘧啶。更重要的是，该方案为制备临床使用的扎来普隆提供了一条简洁的合成路线。
