A concise route to MK-4482 (EIDD-2801) from cytidine.
N Vasudevan1, Grace P Ahlqvist, Catherine P McGeough
1Medicines for All Institute, 737 N. 5th St., Box 980100, Richmond, VA 23298-0100, USA. drsnead@vcu.edu.
Chemical Communications (Cambridge, England)
|October 8, 2020
Summary
A new two-step synthesis of MK-4482 (EIDD-2801) improves yield to 75% and reduces steps. This efficient route uses cytidine, offering a significant advancement in antiviral drug manufacturing.
Area of Science:
- Organic Chemistry
- Medicinal Chemistry
- Process Chemistry
Background:
- MK-4482 (EIDD-2801) is an antiviral compound requiring efficient synthesis.
- Previous synthetic routes were lengthy and low-yielding.
Purpose of the Study:
- To develop an improved, shorter, and more efficient synthetic route to MK-4482 (EIDD-2801).
Main Methods:
- A two-step synthesis involving esterification and hydroxamination of cytidine.
- Selective acylation and direct amination were employed.
Main Results:
- Overall yield increased to 75%, a substantial improvement from 17%.
- The synthetic route was reduced from five steps to two.
- Replaced expensive uridine with more accessible cytidine.
Conclusions:
- The developed two-step route offers a significant advancement for MK-4482 (EIDD-2801) production.
- This method is more efficient, cost-effective, and scalable.
