Journal
ORGANIC PROCESS RESEARCH & DEVELOPMENT
Volume 20, Issue 12, Pages 2028-2042Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.oprd.6b00374
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Synthetic routes and final forms for three recently approved oncology drugs are reviewed: carfilzomib (Kyprolis), osimertinib (Tagrisso), and venetoclax (Vendexta). Several patent applications have been filed for the major synthetic challenge for carfilzomib, installation of the chiral epoxide. The apparent manufacturing route to osimertinib involves seven steps and a longest linear sequence of six steps with a yield of 56%. The apparent manufacturing route to venetoclax is a ten-step convergent synthesis with a seven-step longest linear sequence that proceeds in 52%-yield.
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