Development of the Commercial Manufacturing Process for Ipatasertib

Authors

  • Stephan Bachmann Department of Process Chemistry & Catalysis, Pharma Synthetic Molecules Technical Development, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • Hans Iding Department of Process Chemistry & Catalysis, Pharma Synthetic Molecules Technical Development, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • Christian Lautz Department of Process Chemistry & Catalysis, Pharma Synthetic Molecules Technical Development, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • Isabelle Thomé-Pfeiffer Department of Process Chemistry & Catalysis, Pharma Synthetic Molecules Technical Development, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • Caroline Maierhofer Department of Process Chemistry & Catalysis, Pharma Synthetic Molecules Technical Development, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • Régis Mondière Department of Process Chemistry & Catalysis, Pharma Synthetic Molecules Technical Development, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • Philipp Schmidt Department of Process Chemistry & Catalysis, Pharma Synthetic Molecules Technical Development, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070 Basel, Switzerland
  • Christoph Strasser Dottikon Exclusive Synthesis AG, Hembrunnstrasse 17, CH-5605 Dottikon, Switzerland
  • Thomas Bär Dottikon Exclusive Synthesis AG, Hembrunnstrasse 17, CH-5605 Dottikon, Switzerland
  • André Aebi Dottikon Exclusive Synthesis AG, Hembrunnstrasse 17, CH-5605 Dottikon, Switzerland
  • Andreas Schuster F. Hoffmann-La Roche

DOI:

https://doi.org/10.2533/chimia.2021.605

PMID:

34523401

Keywords:

Biocatalysis, Catalysis, Drug development, Enzyme, Green chemistry, Metal catalysis

Abstract

Ipatasertib is a potent small molecule Akt kinase inhibitor currently tested in Phase III clinical trials for the treatment of metastatic castration-resistant prostate cancer and triple negative metastatic breast cancer. In this paper an overview of the development achievements towards the commercial manufacturing process is given. The convergent synthesis consists of ten steps with eight isolated intermediates and utilizes a wide range of chemical techniques and technologies to build-up this complex drug. All three stereocenters are introduced using enzyme or metal catalysis.

CHIMIA Vol. 75 No. 7-8 (2021): SCS Major Awards / SCS Fall Meeting 2021

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Published

2021-08-17

Issue

Vol. 75 No. 7-8 (2021): SCS Major Awards / SCS Fall Meeting 2021

Section

Scientific Articles

License

Copyright (c) 2021 Andreas Schuster

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

How to Cite

[1]
S. Bachmann, H. Iding, C. Lautz, I. Thomé-Pfeiffer, C. Maierhofer, R. Mondière, P. Schmidt, C. Strasser, T. Bär, A. Aebi, A. Schuster, Chimia 2021, 75, 605, DOI: 10.2533/chimia.2021.605.