A regioselective approach to trisubstituted 2 (or 6)-arylaminopyrimidine-5-carbaldehydes and their application in the synthesis of structurally and electronically unique GlambdaC base precursors.

An efficient regioselective synthesis of trisubstituted 2(or 6)-arylaminopyrimidine-5-carbaldehydes has been developed via an S(N)Ar 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 GlambdaC base precursors.