Route Optimization of the Non-covalent Modulator of Hemoglobin PF-07059013 for the Treatment of Sickle Cell Disease, Part I: From Discovery Synthesis to First Kilogram-Scale Manufacture,Organic Process Research & Development

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Route Optimization of the Non-covalent Modulator of Hemoglobin PF-07059013 for the Treatment of Sickle Cell Disease, Part I: From Discovery Synthesis to First Kilogram-Scale Manufacture
Organic Process Research & Development ( IF 3.4 ) Pub Date : 2023-02-22 , DOI: 10.1021/acs.oprd.2c00351
Aaron Baldwin ₁ , Shawn Cabral ₁ , Kris N. Jones ₁ , Jeffrey T. Kohrt ₁ , Chris Limberakis ₁ , Yiyang Liu ₁ , Javier Magano ₁ , Sebastien Monfette ₁ , Asaad Nematalla ₁ , Sami Ovaska ₁ , David W. Piotrowski ₁ , Jared L. Piper ₁ , Jeffrey W. Raggon ₁ , Benjamin A. Thuma ₁ , Liuqing Wei ₁

Affiliation

The scalable route to PF-07059013 (3), a non-covalent modulator of hemoglobin for the treatment of sickle cell disease, is discussed. Optimization of the discovery route is presented, examining bond connections, late-stage Buchwald–Hartwig C–O coupling, and palladium content reduction strategies. The first process chemistry route to deliver 11 kg of the final API is also discussed.

中文翻译：

用于治疗镰状细胞病的血红蛋白非共价调节剂 PF-07059013 的路线优化，第一部分：从发现合成到首次公斤级生产

讨论了 PF-07059013 ( 3 )的可扩展途径，PF-07059013 是一种用于治疗镰状细胞病的非共价血红蛋白调节剂。介绍了发现路线的优化，检查键连接、后期 Buchwald-Hartwig C-O 耦合和钯含量降低策略。还讨论了提供 11 千克最终 API 的第一种工艺化学路线。

更新日期：2023-02-22

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