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.

中文翻译：

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溶血性贫血药物的替代高效合成工艺：硫酸米他匹瓦


描述了一种用于生产硫酸 mitapivat 的新商业制造工艺，对治疗溶血性贫血至关重要。从 4-硝基苯甲酸 （14） 和 N-Boc 哌嗪 （6） 开始，该过程涉及连续反应以获得叔丁基 4-[4-（喹啉-8-磺酰胺基）苯甲酰基]哌嗪-1-羧酸盐 （7）。然后，该化合物被脱保护，得到 N-[4-（哌嗪-1-羰基）苯基]萘-1-磺酰胺 （8），其经过还原胺化作用，产生不含 mitapivat 的碱 （9）。最后，获得高质量的硫酸 mitapivat，总产率为 81%。合成可防止杂质形成，并采用具有成本效益的原材料，遵守环境可持续性和 ICH 产品质量标准。