Synlett 2021; 32(03): 326-328
DOI: 10.1055/a-1275-2848
letter

A Concise Route to MK-4482 (EIDD-2801) from Cytidine: Part 2

Vijayagopal Gopalsamuthiram
a   Medicines for All Institute, Virginia Commonwealth University, 737 N. 5th St., Box 980100, Richmond, VA, 23298-0100, USA   Email: drsnead@vcu.edu
,
Corshai Williams
b   Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA, 02139, USA
,
Jeffrey Noble
a   Medicines for All Institute, Virginia Commonwealth University, 737 N. 5th St., Box 980100, Richmond, VA, 23298-0100, USA   Email: drsnead@vcu.edu
,
b   Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA, 02139, USA
,
B. Frank Gupton
a   Medicines for All Institute, Virginia Commonwealth University, 737 N. 5th St., Box 980100, Richmond, VA, 23298-0100, USA   Email: drsnead@vcu.edu
,
a   Medicines for All Institute, Virginia Commonwealth University, 737 N. 5th St., Box 980100, Richmond, VA, 23298-0100, USA   Email: drsnead@vcu.edu
› Author Affiliations
We thank the Bill and Melinda Gates Foundation (OPP1176590) for their longstanding support of our research.


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Abstract

A new route to MK-4482 was developed. The route replaces uridine with the more available and less expensive cytidine. Low-cost, simple reagents are used for the chemical transformations, and the yield is improved from 17% to 44%. A step is removed from the longest linear sequence, and these advancements are expected to expand access to MK-4482 should it become a viable drug substance.

Supporting Information



Publication History

Received: 10 September 2020

Accepted after revision: 30 September 2020

Accepted Manuscript online:
30 September 2020

Article published online:
30 October 2020

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