Development of a Convergent Large-Scale Synthesis for Venetoclax, a First-in-Class BCL-2 Selective Inhibitor was written by Ku, Yi-Yin;Chan, Vincent S.;Christesen, Alan;Grieme, Timothy;Mulhern, Mathew;Pu, Yu-Ming;Wendt, Michael D.. And the article was included in Journal of Organic Chemistry in 2019.HPLC of Formula: 179232-29-2 This article mentions the following:
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 (2 tert-Bu ester) 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. In the experiment, the researchers used many compounds, for example, Methyl 4-bromo-2-fluorobenzoate (cas: 179232-29-2HPLC of Formula: 179232-29-2).
Methyl 4-bromo-2-fluorobenzoate (cas: 179232-29-2) belongs to organobromine compounds. Bromo compounds are employed in a variety of metal-catalyzed coupling reactions. They are also ideal candidates for the synthesis of Grignard reagents that have wide-applicability in organic synthesis. alpha-Bromoesters are employed in the Reformatsky reaction for the synthesis of beta-hydroxyesters. Bromine-containing agents predominate because not only are they more efficient than similar chlorine-containing species, but also the high atomic weight of bromine ensures that it is present in a high mass fraction within most organobromine compounds.HPLC of Formula: 179232-29-2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary