First Multikilogram Synthesis of the Next-Generation Oral Selective ERα Degrader Camizestrant

Camizestrant is currently being investigated in multiple Phase 3 clinical trials for ER+ breast cancer. This article describes our efforts toward the first manufacture of clinical material. Strategic process development focused on delivering robust processes and control points that could be scaled to deliver kilograms of material of the right quality and meet expedited project timelines. Highlights include optimization of an efficient Buchwald–Hartwig amination, development of a diastereoselective Pictet–Spengler reaction followed by an efficient isolation, and a significant reduction in the number of chromatography stages from five to one. The processes were used to deliver 8.5 kg of material in an overall yield of 44%.