Process Development\nto Synthesize SGD-11275 Utilizing\na Pd-Catalyzed Acetamide Arylation and Gallium-Mediated Friedel–Crafts\nAcylation

An\nimproved synthesis of SGD-11275 was developed to address inefficiencies\nin cost, time, and safety associated with the previous supply route.\nThe new route features a Buchwald-Hartwig amination with acetamide\noptimized by high-throughput experimentation as well as a GaCl<sub>3</sub>-mediated Friedel–Crafts acylation. Subsequent amide\nhydrolysis was demonstrated from the isolated Friedel–Crafts\nproduct and as a through-process with equal effectiveness. The new\nroute reduced the commercial synthesis by three steps and increased\nthe overall yield by 18.6%.