An Alternate, Efficient Synthetic Process for a Hemolytic Anemia Drug: Mitapivat Sulfate

A new commercial manufacturing process for producing mitapivat sulfate, crucial for treating hemolytic anemia, is described. Starting from 4-nitrobenzoic acid (14) and N-Boc piperazine (6), the process involves sequential reactions to obtain tert-butyl 4-[4-(quinoline-8-sulfonamido)benzoyl]piperazine-1-carboxylate (7). This compound is then deprotected to yield N-[4-(piperazine-1-carbonyl)phenyl]naphthalene-1-sulfonamide (8), which undergoes reductive amination to produce mitapivat-free base (9). Finally, mitapivat sulfate is obtained with high quality and an overall yield of 81%. The synthesis prevents impurity formation and employs cost-effective raw materials, adhering to environmental sustainability and ICH product quality standards.