Key Laboratory of Drug-Targeting and Drug-Delivery Systems of the Ministry of Education, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
J Org Chem. 2012 Mar 16;77(6):2649-58. doi: 10.1021/jo2023697. Epub 2012 Feb 24.
An efficient route to N(4)-substituted 2,4-diaminoquinazolines has been developed by employing tandem condensation of cyanoimidate-amine and reductive cyclization in iron-HCl system. This method is tolerant of a following intramolecular N-alkylation and produces two fused heterocycles in a one-pot procedure. This protocol is a facile two-step synthesis of tricyclic quinazolines, which is effected by potent cyanoimidation and tandem reductive cyclization from 2-nitrobenzaldehydes. Moreover, the forming process of tricyclic quinazolines has been investigated from the ring-opening/ring-closing cascade point of view. It is found that the preparation of tricyclic quinazolinones in good yields relies on the selective hydrolysis of tricyclic quinazolines in base or acid system.
通过在铁-HCl 体系中采用氰基亚氨基-胺的串联缩合和还原环化反应，开发了一种高效的 N(4)-取代 2,4-二氨基喹唑啉的方法。该方法耐受后续的分子内 N-烷基化反应，并在一锅法中生成两个稠合杂环。该方案是通过强氰基亚氨化和 2-硝基苯甲醛的串联还原环化作用，从 2-硝基苯甲醛出发，简便地两步合成三环喹唑啉。此外，还从开环/闭环级联的角度研究了三环喹唑啉的形成过程。结果发现，在碱性或酸性体系中，通过选择性水解三环喹唑啉，可以以良好的收率制备三环喹唑啉酮。
