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A Potential Practical Process for Remdesivir

preprint
submitted on 01.06.2021, 08:04 and posted on 08.06.2021, 08:20 by Chen Liujuan, Guowei Zhang, Jinguang Liu, Jianye Jiao, Han Lin, Miao Wu, Xin Zhang
A four-step synthesis of Remdesivir (1) is presented. This work focuses on the yield improvement of step 1, flow chemistry development of step 2 and 3, process optimization of step 4. The literatures reported (https://dx.doi.org/10.1021/acs.oprd.0c00310 and https://dx.doi.org/10.1021/acs.oprd.0c00172: SI part) step 1 was repeated, but failed in the crystallization, eventually step 1 product was obtained by column chromatography with >98% HPLC purity and 40% IY. The flow chemistry development of step 2(IY: 84%) and 3 (IY: 63%) was achieved and the release of toxic HCN was avoided, the process robustness was improved by flow chemistry. Step 4 was simplified to apply primary alcohol 6 directly (without protection) to react with chiral SM 8. Lewis acid catalysts were screened by HTS and MgI2 gave 50% AY. Cheap and commercially available MgCl2 and NaI were used to replace MgI2, finally Remdesivir (1) was obtained in >99% purity with 40.3% IY.

Funding

To enable a lower cost process for production of Remdesivir API

Bill & Melinda Gates Foundation

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History

Email Address of Submitting Author

chenliujuan@asymchem.com.cn

Institution

Asymchem Life Science (Tianjin) Co., Ltd.

Country

China

ORCID For Submitting Author

0000-0003-2611-5650

Declaration of Conflict of Interest

No conflict of interest

Version Notes

version 1.0

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