Process Development to Synthesize SGD-11275 Utilizing a Pd-Catalyzed Acetamide Arylation and Gallium-Mediated Friedel–Crafts Acylation

An improved synthesis of SGD-11275 was developed to address inefficiencies in cost, time, and safety associated with the previous supply route. The new route features a Buchwald-Hartwig amination with acetamide optimized by high-throughput experimentation as well as a GaCl3-mediated Friedel–Crafts acylation. Subsequent amide hydrolysis was demonstrated from the isolated Friedel–Crafts product and as a through-process with equal effectiveness. The new route reduced the commercial synthesis by three steps and increased the overall yield by 18.6%.