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Toward Secure Supply of Remdesivir via a 2-Pot Triazine Synthesis: Supply Centered Synthesis

submitted on 01.08.2020, 22:42 and posted on 10.08.2020, 06:40 by Dinesh J. Paymode, Flavio S. P. Cardoso, Joshua D. Sieber, John W. Tomlin, Daniel W. Cook, Justina Burns, Rodger W. Stringham, B. Frank Gupton, David Snead, Toolika Agrawal
Pyrrolotriazine 1 is an important precursor to Remdesivir, and an efficient synthesis is disclosed. This route features atom economy and reduced derivatization of starting materials, by making use of highly abundant, commoditized raw material inputs. The yield of triazine was doubled from 31% to 59%, and the synthetic step count was reduced from 4 to 2. A one-pot cascade sequence was developed for direct cyanation of pyrrole. Amination and cyclization with formamidine acetate complete the synthesis. The problematic nature of typically dilute electrophilic aminations was solved with semi-continuous processing. Moreover, development of a continuous platform afforded access to the ideal yet non-commercial aminating reagent, monochloramine. These efforts help to secure the Remdesivir supply chain.


Bill and Melinda Gates Foundation (BMGF) OPP1176590


Email Address of Submitting Author


Medicines for All Institute, Virginia Commonwealth University


United States of America

ORCID For Submitting Author


Declaration of Conflict of Interest

The authors declare no competing financial interests.

Version Notes

Joshua D. Sieber added to list of authors and email address corrected with figshare.