A Scalable Synthesis of Roxadustat (FG-4592)
Organic Process Research & Development(2022)
摘要
A scalable five-step protocol for synthesis of roxadustat, an orally administered hypoxia-inducible factor-propyl hydroxylase inhibitor (HIF-PHI), was developed with an emphasis placed on aspects of medicinal chemistry. The isoquinoline core of the molecule was prepared using a purposefully designed cyclocondensation in which both the cyclocondensation and demasking of the groups being condensed is promoted by a common acid agent in one step. Roxadustat was obtained pure in a very competitive overall yield across all reaction steps and in compliance with permissible residual Pd level in API.
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关键词
roxadustat,isoquinoline synthesis,HIF inhibitors,scalable protocol,API synthesis,pharmaceutical quality
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