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. 2023 Mar 29;9(5):849-857.
doi: 10.1021/acscentsci.3c00145. eCollection 2023 May 24.

Development of the Commercial Manufacturing Process for Nirmatrelvir in 17 Months

Christophe Allais  1 , Christina G Connor  1 , Nga M Do  1 , Samir Kulkarni  1 , Johnny W Lee  1 , Taegyo Lee  1 , Emma McInturff  1 , Jared Piper  1 , Dave W Place  1 , John A Ragan  1 , R Matt Weekly  1
Affiliations

Development of the Commercial Manufacturing Process for Nirmatrelvir in 17 Months

Christophe Allais et al. ACS Cent Sci. .

Abstract

The advancement of nirmatrelvir, the active ingredient in Paxlovid, from discovery to emergency use authorization was achieved in just 17 months, requiring an unprecedented rate of chemical process development.

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Conflict of interest statement

The authors declare the following competing financial interest(s): The authors are employees of Pfizer, Inc. and have been engaged in the development and manufacture of nirmatrelvir.

Figures

Figure 1
Figure 1
Overview of project challenges.
Figure 2
Figure 2
Development timeline comparisons.
Figure 3
Figure 3
Final bond forming sequence to nirmatrelvir (1).
Figure 4
Figure 4
Synthesis of dipeptide 4.
Figure 5
Figure 5
PF-07321332 building blocks.
Figure 6
Figure 6
Synthetic routes to bicyclic pyrrolidine building block 6.
Figure 7
Figure 7
Synthesis of trifluoroacetamide 11.
Figure 8
Figure 8
Protease inhibitors containing the chiral lactam moiety.
Figure 9
Figure 9
(a) Lithium dianion alkylation to control lactam stereochemistry. (b) Synthesis of carboxamide 3.
Figure 10
Figure 10
Supply chain for starting materials 3, 6, and 11.
Figure 11
Figure 11
Current synthesis of nirmatrelvir.
See this image and copyright information in PMC

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