Development of a sp 2 -sp 3 Stille Cross-Coupling for Rapid Synthesis of HIV NNRTI Doravirine Analogues.

The development of a C(sp2 )-C(sp3 ) cross-coupling reaction for rapid, parallel synthesis of analogues of two HIV NNRTI clinical candidates is described. This method allowed easy access to the C-ring space using a practical alkylation with commercially available tributyl(iodomethyl)stannane followed by a palladium-catalyzed coupling with a variety of aryl halides (I, Br) in the presence of copper chloride. Optimization and scope of this method are reported.