op3c00249_si_001.pdf (919.51 kB)
Synthesis of Nirmatrelvir: Development of an Efficient, Scalable Process to Generate the Western Fragment
journal contribution
posted on 2023-11-25, 13:03 authored by Russell
F. Algera, Christophe Allais, Aaron F. Baldwin, Husein Becirovic, Paul Bowles, Adam R. Brown, Jamie M. Buske, Hugh J. Clarke, Nga M. Do, Kevin Doyle, Jonathan Fifer, Kaitlyn Gray, Alan Happe, Mark Hardink, Aran K. Hubbell, Chintelle James, Hrushikesh P. Khadamkar, Javier Magano, Emma L. McInturff, Jason Mustakis, Gizem Ozbuyukkaya, Jared L. Piper, David W. Place, John A. Ragan, Blake Rauschenberger, Giselle Reyes, Rawan Shehadeh, Corey Stanchina, Michael Stanley, R. Matthew Weekly, Ethan Weinstein, Gerald A. Weisenburger, Ethan Wood, Hatice G. Yayla, Shu YuNirmatrelvir (1), a novel and specific inhibitor
of
the SARS-CoV-2 3C-like protease, was developed by Pfizer scientists
in mid 2020. Efforts to develop a scalable process to manufacture
nirmatrelvir were undertaken with a great sense of urgency, as there
were no effective treatments available for the worldwide patient population
at that time. We used a convergent approach to generate this molecule.
The first two steps used to generate the western fragment of nirmatrelvir
from l-tert-leucine, ethyl trifluoroacetate,
and a [3.1.0] bicyclic proline derivative are described here. This
is the first of a series of four papers describing the commercial
process of the development of nirmatrelvir.
