Chemistry Seminar Series: Dan FishlockExport this event to calendar

Wednesday, October 10, 2018 — 10:00 AM EDT

Development of the Cu(I)-catalyzed [3+2] Asymmetric Cycloaddition Process for the Manufacture of Idasanutlin

Dr. Dan Fishlock
F. Hoffmann-La Roche
Switzerland

Wednesday, October 10, 2018
10:00 a.m.
C2-361 (Reading Room)

Abstract:  A concise asymmetric synthesis has been developed to prepare idasanutlin (1), a small molecule MDM2 antagonist 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)/BINAP catalyzed [3+2]-cycloaddition reaction. This optimized copper(I) catalyzed process has been used to produce more than 1500 kg of idasanutlin.

line drawing of idasanutlin molecule

The evolution of this synthetic route from the laboratory to commercial-scale manufacturing 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.


 

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