From vials to reactors: Catalyzing innovation in process development

Abstract: Process development for Repotrectinib (BMS-986472) exemplifies how innovative strategies can advance sustainable pharmaceutical manufacturing. By integrating green chemistry principles, the team transformed the synthetic route to this API, achieving a fourfold increase in overall yield (11% to 45%), reducing isolations from 10 to 6, and eliminating dioxane and all halogenated solvents and reagents. The second generation process underscores the importance of deep process understanding of the reaction conditions, workup, and isolation, combined with modeling and optimization to ensure robust scalability, reflecting a commitment to delivering scalable, sustainable solutions for complex drug synthesis.