Scheme 1. Synthesis of Clinical Candidate CMX990: A) Synthesis of the Novel Trifluoromethoxymethyl Ketone Warhead Bearing P1 Unit (19) and B) Core Synthetic Route for CMX990.

The novel warhead-containing P1 fragment (19) can be manufactured at multi-kilogram scales at >98% purity and stored long-term. The CMX990 manufactured using this process is a white crystalline solid, readily amenable for suspension formulation development as well as solid dosage form development.