Pd-Catalyzed Heteroannulation Route to 4-Aminoquinazolines via C-H Amidination

Significance

A concise synthesis of 4-aminoquinazolines is presented, which involves palladium-catalyzed intramolecular aryl C-H amidination by isonitrile insertion. Starting from easily available N-arylamidines and isonitriles, the reaction proceeds under mild conditions to afford substituted 4-aminoquinazolines with a broad substrate scope and good functional group tolerance in moderate to excellent yields. Notably, sterically hindered isonitriles such as tert-butyl and 2,6-dimethylphenylisonitriles worked well for this process. An advantage of the methodology is the ready availability of the starting materials from commercial aniline derivatives.