A Streamlined, Safe and Sustainable Process for Gemlapodect

Abstract The research efforts to attain a suitable process for the timely delivery of Gemlapodect for initial toxicological and phase 1/2 clinical studies are described. The original discovery chemistry route was hampered by considerable safety issues and low overall yield. The safety issues were solved by the introduction of a copper‐catalyzed oxidative cyclization while a novel process for the synthesis of the pyrazole building block as well as the implementation of a palladium‐catalyzed coupling between the pyrazole amide and the bromo‐triazolopyridine scaffolds contributed to improve the route efficiency. Overall, a safe and sustainable process was attained that allowed the production of up to 19.2 kg of drug substance with a reduced number of steps and an increased overall yield.