Plenary Lecture, Award Lecture
PS-002

Development of the Commercial Manufacturing Process for Ipatasertib

A. Schuster1,2, S. Bachmann1, H. Iding1, C. Lautz1, I. Thomé-Pfeiffer1, C. Maierhofer1, R. Mondière1, P. Schmidt1, C. Strasser1
1Department of Process Chemistry & Catalysis, Pharma Small Molecules Technical Development, F. Hoffmann-La Roche AG, Grenzacherstrasse 124, CH-4070 Basel, Switzerland, 2

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 presentation an overview of the development activities towards the commercial manufacturing process is given. The convergent synthesis comprises ten steps with eight isolated intermediates and utilizes a wide range of chemical techniques and technologies to build this complex drug. All three stereocenters are introduced using enzyme as well as metal catalysis.

[1] Remarchuk, S. Babu, J. Stults, A. Zanotti-Gerosa, S. Roseblade, S. Yang, P. Huang, C. Sha, and Y. Wang, Org. Process Res. Dev. 2014, 18, 1641−1651.
[2] Remarchuk, F. St-Jean, D. Carrera, S. Savage, H. Yajima, B. Wong, S. Babu, A. Deese, J. Stults, M. W. Dong, D. Askin, J. W. Lane, and K. L. Spencer, Org. Process Res. Dev. 2014, 18, 1652−1666.