Related Experiment Video
Updated: Aug 25, 2026

Synthesis and Bioconjugation of Thiol-Reactive Reagents for the Creation of Site-Selectively Modified Immunoconjugates
Published on: March 6, 2019
A Highly Atroposelective Negishi Coupling Enables the Commercial Manufacturing Process of Divarasib
Stephan Bachmann1, Raphael Bigler1, Danis Kaldre1
1Synthetic Molecules Technical Development, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland.
None:
In this publication, we highlight our development efforts that resulted in the commercial manufacturing route of divarasib (1), a highly potent KRAS G12C inhibitor currently undergoing phase III clinical trials. Most prominently, our process landmarks, the first example of a highly atroposelective Negishi coupling at scale, allowing isolation of the step product (Ra)-4 as a single isomer without chromatography. The implementation of a continuous process for the metalation steps of the atroposelective Negishi coupling allowed for the elimination of the cryogenic reaction conditions from the manufacturing process. Furthermore, we detail improvements for the other chemical steps resulting in an impressive yield increase (factor of 6) and process mass intensity (PMI) reduction (factor of 39) for this sequence.
More Related Videos
Related Concept Videos
Production of Pharmaceuticals
Aryldiazonium Salts to Azo Dyes: Diazo Coupling
Drug Biotransformation: Overview
Drug Biotransformation: Overview
Clinically Relevant Drug Product Specifications: Methods of Establishment
Site-Targeted Drug Delivery Systems: Polymeric Carriers

