Efficient Industrial Synthesis of the MDM2 Antagonist Idasanutlin via a Cu(I)-catalyzed [3+2] Asymmetric Cycloaddition
Keywords:Asymmetric synthesis, Catalysis, Cycloaddition, Process chemistry
AbstractA concise asymmetric synthesis has been developed to prepare idasanutlin, a small molecule MDM2 antagonist. Idasanutlin is currently being investigated as a potential treatment for various solid tumors and hematologic malignancies. The highly congested pyrrolidine core, containing four contiguous stereocenters, was constructed via a Cu(I)/(R)-BINAP catalyzed [3+2]-cycloaddition reaction. This optimized copper(I)-catalyzed process has been used to produce more than 1500 kg of idasanutlin. The manufacturing process will be described, highlighting the exceptionally selective and consistent cycloaddition/isomerization/hydrolysis sequence. The excellent yields, short cycle times and reduction in waste streams result in a sustainable production process with low environmental impact.
How to Cite
D. Fishlock, R. Diodone, S. Hildbrand, B. Kuhn, C. Mössner, C. Peters, P. D. Rege, G. Rimmler, M. Schantz., Chimia 2018, 72, 492, DOI: 10.2533/chimia.2018.492.
Copyright (c) 2018 Swiss Chemical Society
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.