A 1-Pot Synthesis of the SARS-CoV-2 Mpro Inhibitor Nirmatrelvir, the Key Ingredient in Paxlovid

Juan C Caravez; Karthik S Iyer; Rahul D Kavthe; Joseph R A Kincaid; Bruce H Lipshutz

doi:10.1021/acs.orglett.2c03683

A 1-Pot Synthesis of the SARS-CoV-2 M^pro Inhibitor Nirmatrelvir, the Key Ingredient in Paxlovid

Org Lett. 2022 Dec 16;24(49):9049-9053. doi: 10.1021/acs.orglett.2c03683. Epub 2022 Dec 7.

Authors

Juan C Caravez¹, Karthik S Iyer¹, Rahul D Kavthe¹, Joseph R A Kincaid¹, Bruce H Lipshutz¹

Affiliation

¹ Department of Chemistry & Biochemistry, University of California, Santa Barbara, Santa Barbara, California 93106, United States.

Abstract

A newly devised route to the Pfizer drug nirmatrelvir is reported that reduces the overall sequence to a 1-pot process and relies on a commercially available, green coupling reagent, T3P. The overall yield of the targeted material, isolated as its MTBE solvate, is 64%.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / pharmacology
COVID-19*
Drug Combinations
Humans
Lactams
Leucine
Nitriles
Proline
Ritonavir
SARS-CoV-2*

Substances

Leucine
Antiviral Agents
nirmatrelvir and ritonavir drug combination
Drug Combinations
Lactams
Nitriles
Proline
Ritonavir