Synthesis of belumosudil

Abstract We developed a novel synthetic route to belumosudil featuring an oxidative cyclization of anthranilamide with meta ‐substituted benzaldehyde as the key step for constructing the quinazolinone scaffold. Alkylation of 3‐hydroxybenzaldehyde with 2‐chloroacetamide furnished a benzaldehyde derivative bearing the desired meta ‐substituent. Subsequent metal‐free aerobic oxidative cyclization of anthranilamide and the aldehyde in DMSO afforded the desired quinazolinone. Treatment with POCl 3 converted the quinazolinone intermediate into the corresponding quinazolinyl chloride, which was then coupled with 5‐aminoindazole to complete the synthesis of belumosudil.