Efficient Industrial Synthesis of the MDM2 Antagonist Idasanutlin via a Cu(I)-catalyzed [3+2] Asymmetric Cycloaddition
DOI:
https://doi.org/10.2533/chimia.2018.492Keywords:
Asymmetric synthesis, Catalysis, Cycloaddition, Process chemistryAbstract
A 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.Downloads
Published
2018-08-22
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Scientific Articles
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Copyright (c) 2018 Swiss Chemical Society
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How to Cite
[1]
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.