芳基
催化作用
组合化学
烷基化
分子内力
化学
计算机科学
有机化学
烷基
作者
James Kempson,Xiaoping Hou,Jianqing Li,Eric M. Simmons,Wei Meng,Jon J. Hangeland,Pratik Devasthale
标识
DOI:10.1021/acs.oprd.2c00036
摘要
This paper describes the efficient scale-up synthesis of 1 (BMS-963272) which relies upon a highly selective Mannich-type alkylation strategy to stereospecifically install a quaternary carbon center. An intramolecular cyclization reaction is also used to form the aryl dihydropyridone (ADHP) core. The optimized route has been demonstrated to provide more than 100 g of active pharmaceutical ingredient for preclinical toxicology evaluation. A catalyst screening effort is also discussed as part of a complimentary convergent approach which will facilitate a more expedient assessment of back-up molecules bearing aryl diversity at the C4-position of the ADHP core.
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