A High-Yielding Synthesis of EIDD-2801 from Uridine

Alexander Steiner; Desiree Znidar; Sándor B Ötvös; David R Snead; Doris Dallinger; C Oliver Kappe

doi:10.1002/ejoc.202001340

A High-Yielding Synthesis of EIDD-2801 from Uridine

European J Org Chem. 2020 Nov 22;2020(43):6736-6739. doi: 10.1002/ejoc.202001340. Epub 2020 Nov 12.

Authors

Alexander Steiner^{1

2}, Desiree Znidar^{1

2}, Sándor B Ötvös^{1

2}, David R Snead³, Doris Dallinger^{1

2}, C Oliver Kappe^{1

2}

Affiliations

¹ Institute of Chemistry University of Graz, NAWI Graz Heinrichstrasse 28 8010 Graz Austria.
² Center for Continuous Flow Synthesis and Processing (CCFLOW) Research Center Pharmaceutical Engineering GmbH (RCPE) Inffeldgasse 13 8010 Graz Austria.
³ Medicines for All Institute 737 N. 5 23298-0100 Richmond Virginia USA.

Abstract

A simple reordering of the reaction sequence allowed the improved synthesis of EIDD-2801, an antiviral drug with promising activity against the SARS-CoV-2 virus, starting from uridine. Compared to the original route, the yield was enhanced from 17 % to 61 %, and fewer isolation/purification steps were needed. In addition, a continuous flow procedure for the final acetonide deprotection was developed, which proved to be favorable toward selectivity and reproducibility.

Keywords: Acetonide deprotection; COVID‐19; Continuous flow; EIDD‐2801; Triazolation.