889858-12-2Relevant articles and documents
Method for synthesizing high-purity tert-butyl 2-fluoro-4-bromobenzoate
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Paragraph 0028-0033, (2021/08/19)
The invention discloses a method for synthesizing high-purity tert-butyl 2-fluoro-4-bromobenzoate, which comprises the following steps: synthesizing a compound 2-fluorine-4-bromobenzoyl chloride from 2-fluorine-4-bromobenzoic acid, then synthesizing the t
Method for synthesizing key intermediate of venetoclax
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Paragraph 0017; 0019; 0021, (2020/11/23)
The invention relates to the technical field of medicine synthesis, in particular to a method for synthesizing a key intermediate of venetoclax. The method comprises the following steps: with 4-bromo-2-fluorobenzoic acid (I) as a raw material, carrying ou
Development of a Convergent Large-Scale Synthesis for Venetoclax, a First-in-Class BCL-2 Selective Inhibitor
Ku, Yi-Yin,Chan, Vincent S.,Christesen, Alan,Grieme, Timothy,Mulhern, Mathew,Pu, Yu-Ming,Wendt, Michael D.
, p. 4814 - 4829 (2019/02/05)
The process development of a new synthetic route leading to an efficient and robust synthetic process for venetoclax (1: the active pharmaceutical ingredient (API) in Venclexta) is described. The redesigned synthesis features a Buchwald-Hartwig amination to construct the core ester 23c in a convergent fashion by connecting two key building blocks (4c and 26), which is then followed by a uniquely effective saponification reaction of 23c using anhydrous hydroxide generated in situ to obtain 2. Finally, the coupling of the penultimate core acid 2 with sulfonamide 3 furnishes drug substance 1 with consistently high quality. The challenges and solutions for the key Pd-catalyzed C-N cross-coupling will also be discussed in detail. The improved synthesis overcomes many of the initial scale-up challenges and was accomplished in 46% overall yield from 3,3-dimethyldicyclohexanone (6), more than doubling the overall yield of the first generation route. The new process was successfully implemented for producing large quantities of 1 with >99% area purity.