A Regioselective Approach to Trisubstituted 2 (or 6)-Arylaminopyrimidine-5-carbaldehydes and Their Application in the Synthesis of Structurally and Electronically Unique G∧C Base Precursors

An efficient regioselective synthesis of trisubstituted 2(or 6)-arylaminopyrimidine-5-carbaldehydes has
been developed via an SNAr reaction of 2,4,6-trichloropyrimidine-5-carbaldehyde with aniline, methylamine, and alkoxide nucleophiles using a combination of phase-transfer catalysis and more traditional
SNAr reaction conditions. We demonstrate that in a few synthetic steps, highly functionalized fused-bicyclic pyrimidine substrates can be accessed from the trisubstituted 2-arylaminopyrimidine-5-carbaldehydes. Furthermore, these fused-bicyclic compounds are readily derivatized using the Suzuki
cross-coupling reaction to generate electronically and structurally unique G∧C base precursors.

本研究开发出一种高效的区域选择性合成三取代2（或6）-芳氨基嘧啶-5-甲醛的方法：以2,4,6-三氯嘧啶-5-甲醛与苯胺、甲胺及醇盐亲核试剂为反应底物，结合相转移催化与经典亲核芳香取代（SNAr）反应条件完成转化。我们证实，仅需数步合成反应，即可由该三取代2-芳氨基嘧啶-5-甲醛制备得到高官能化的稠合双环嘧啶类底物。此外，此类稠合双环化合物可借助铃木交叉偶联（Suzuki cross-coupling）反应轻松实现衍生化，进而得到电子特性与结构均独具特色的G∧C碱基前体。