Development of a Process to a 4-Arylated 2-Methylisoquinolin-1(2H)-one for the Treatment of Solid Tumors: Lessons in Ortho-Bromination, Selective Solubility, Pd Deactivation, and Form Control was written by Primer, David N.;Yong, Kelvin;Ramirez, Antonio;Kreilein, Matthew;Ferretti, Antonio C.;Ruda, Antonio M.;Fleary-Roberts, Nadia;Moseley, Jonathan D.;Forsyth, Sian M.;Evans, Graham R.;Traverse, John F.. And the article was included in Organic Process Research & Development in 2022.Category: bromides-buliding-blocks This article mentions the following:
Presented an optimized, scalable synthesis of bromodomain and extra-terminal (BET) inhibitor BMS-986378 (CC-90010). The original route and process 1A was 7 steps with 33.8% yield and featured numerous problematic solvents, process safety concerns, difficult to scale unit operations and challenging to control impurities. Reaction optimization to remove or mitigate these challenges resulted in first scale-up route and process, 2A. Subsequent challenges encountered on scale-up of route and process 2A warranted the creation and implementation of an enhanced process, which eliminated dichloromethane from a phenol bromination, improved catalyst performance in the penultimate cross-coupling and finally developed a concomitant solvent charging process for form control in the final API crystallization The resulting scale-up route and process, 2B, were demonstrated on a >50 kg scale and afforded the final product in 49% yield over 7 steps in >99.9% assay and area purity, meeting all ICH requirements for quality. In the experiment, the researchers used many compounds, for example, 1-Bromopyrrolidine-2,5-dione (cas: 128-08-5Category: bromides-buliding-blocks).
1-Bromopyrrolidine-2,5-dione (cas: 128-08-5) belongs to organobromine compounds. A variety of minor organobromine compounds are found in nature, but none are biosynthesized or required by mammals. Organobromine compounds have fallen under increased scrutiny for their environmental impact. Many of the alkyl bromine derivatives are excellent alkylating agents since bromides are good leaving groups. Tribromides, like tetrabutylammonium tribromide, are used as a solid source of bromine. N-bromosuccimide (NBS) is used for the selective bromination of allylic bonds.Category: bromides-buliding-blocks
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary