Synthesis of pyrimidine-fused skeletons through copper-catalyzed consecutive Sonogashira coupling and aminocyclization.

A copper-catalyzed sequence involving a Sonogashira coupling reaction and 5- exo-dig aminocyclization between a terminal alkyne and a 2-(2-bromophenyl)pyrimidine analog based on six-membered rings is presented. This protocol provides a controlled and modular approach to access a variety of synthetically useful pyrimidine-fused skeletons with high efficiency, broad substrate scope, and excellent functional group compatibility. Under acidic conditions, the ( Z )-configuration of products spontaneously converts into ( E )-9-benzylidene-1,9-dihydro-11 H -pyrazolo[4',3':4,5]pyrimido[2,1- a ]isoindol-11-ones.