A concise and practical route to Gedatolisib via a continuous-flow Kumada coupling reaction.

A practical three-step route to Gedatolisib, a dual PI3K/mTOR inhibitor for breast cancer, has been developed, featuring a key continuous-flow iron-catalyzed Kumada coupling. This continuous-flow setup enhances heat and mass transfer, eliminates the need for noble metal catalysts and associated removal steps. This approach avoids hazardous reagents as well as high-boiling solvents, thereby improving both safety and scalability. The 100 gram scale synthesis affords Gedatolisib in 66% overall yield (98.9% purity), featuring mild conditions and crystallization-based purification, offering lower costs and better scalability for industrial production.