A C–H activation reaction was developed using imidazo[1,2-a]pyridine adducts via an AgOAc-mediated, Pd catalyzed intramolecular cyclization. The reaction was optimized and extensively explored using the Ugi/azide MCR as a tool to rapidly broaden substrate scope. Title compounds were screened against a cancer cell panel, and 6af exhibited selective, antiproliferative activity against the MCF-7 (breast cancer) cell line. This C–H activation methodology can be utilized to rapidly reach new chemical-space for drug discovery.