Academia / Industry Collaborations towards the Functionalization of Aryl Azoles

Authors

  • Simon Wagschal Lonza
  • Diego Broggini Chemical Process Research and Development, Janssen Pharmaceutica, Hochstrasse 201, Schaffhausen CH-8200, Switzerland

DOI:

https://doi.org/10.2533/chimia.2024.104

PMID:

38547010

Keywords:

Aryl azoles, Metalation, Milvexian, Triazoles

Abstract

Aryl azoles can be found in numerous active pharmaceutical ingredients (APIs). Milvexian is a Factor Xia inhibitor currently in phase III for the treatment of thrombotic events containing an ortho-substituted 1-aryl-1H-1,2,3-triazole moiety. During the process development of Milvexian, we assessed multiple approaches for the preparation of 4-chloro-1,2,3-triazole, intermediate 1. In this review article, we will detail how we initiated several academic collaborations to speed up the selection of the best synthesis for commercial manufacturing. Ultimately, those results not only helped us to achieve our goal but yielded general methodologies for the functionalization of azoles that extended even beyond our initial scope.

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Published

2024-03-27