Combinatorial synthesis of substituted pyrazolo-fused quinazolines by the Rh(III)-catalyzed [5 + 1] annulation of phenyl-1 H -pyrazol-5-amine with alkynoates and alkynamides

A Rh(III)-catalyzed C-H activation/cyclization cascade was developed for the first divergent synthesis of pyrazolo[1,5- ]quinazolines through a [5 + 1] annulation reaction exclusively. The one-pot procedure is recognized for its broad substrate scope, functional group tolerance, and high atom economy. Mechanistic studies reveal the reaction pathway, addressing current limitations. Notably, this catalytic transition metal-assisted tandem annulation smoothly proceeds through the reaction of substituted phenyl-1 -pyrazol-5-amine with an alkyne ester or amide, where a one ring carbon is provided by the alkynoate building block. This transformation highlights the potential of transition metal-catalyzed methods for synthesizing diverse pyrazolo[1,5- ]quinazoline frameworks.