Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Nov 22;2020(43):6736-6739.
doi: 10.1002/ejoc.202001340. Epub 2020 Nov 12.

A High-Yielding Synthesis of EIDD-2801 from Uridine

Alexander Steiner  1   2 , Desiree Znidar  1   2 , Sándor B Ötvös  1   2 , David R Snead  3 , Doris Dallinger  1   2 , C Oliver Kappe  1   2
Affiliations

A High-Yielding Synthesis of EIDD-2801 from Uridine

Alexander Steiner et al. European J Org Chem. .

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.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1
Patented route (a) vs. proposed route (b) toward EIDD‐2801.
Scheme 2
Scheme 2
Step 1: Triazolation of uridine.
Scheme 3
Scheme 3
Steps 2 and 3: One‐pot acetonide protection and esterification. See the Supporting Information for more details.
Scheme 4
Scheme 4
Step 4: Hydroxylamine formation.
Figure 1
Figure 1
Steps 4 and 5: Telescoped batch hydroxyamination and continuous flow acetonide deprotection. (A) Schematic representation of the reaction set‐up. (B) Structures of identified side products.
Scheme 5
Scheme 5
Improved protocol for the synthesis of EIDD‐2801.
See this image and copyright information in PMC

References

    1. https://www.who.int/emergencies/diseases/novel‐coronavirus‐2019 (accessed October 7, 2020).
    1. Sheahan T. P., Sims A. C., Zhou S., Graham R. L., Pruijssers A. J., Agostini M. L., Leist S. R., Schäfer A., Dinnon K. H., Stevens L. J., Chappell J. D., Lu X., Hughes T. M., George A. S., Hill C. S., Montgomery S. A., Brown A. J., Bluemling G. R., Natchus M. G., Saindane M., Kolykhalov A. A., Painter G., Harcourt J., Tamin A., Thornburg N. J., Swanstrom R., Denison M. R. and Baric R. S., Sci. Transl. Med, 2020, 12, 5883. - PMC - PubMed
    1. https://www.clinicaltrials.gov/ct2/show/NCT04405570?intr=EIDD‐2801&draw=2 (accessed October 7, 2020).
    1. https://www.trialsitenews.com/merck‐positioning‐to‐take‐the‐lead‐u‐s‐cov... (accessed October 7, 2020).
    1. Painter G. R., Bluemling G. R., Natchus M. G. and Guthrie D., N4‐Hydroxy Cytidine and Derivatives and Anti‐Viral Uses Related Thereto, 2019, WO2019113462A1.

LinkOut - more resources