试剂
立体中心
烷基化
组合化学
对映选择合成
化学
立体化学
有机化学
催化作用
作者
Jeffrey M. Kallemeyn,J. B. Hartung,Timothy Connolly,Andrew R. Ickes,Brian J. Kotecki,Leon van Haandel,Milad Nazari,Onkar N. Manjrekar,Shuang Chen
标识
DOI:10.1021/acs.oprd.2c00245
摘要
Challenges in the synthesis of the cystic fibrosis transmembrane receptor corrector ABBV-3748 were addressed to enable a multikilogram-scale GMP sequence. Implementation of an early-stage telescoped titanium-mediated alkylation and palladium-catalyzed hydrogenation limited the formation of a dimerization impurity and provided consistent yields across reaction scales. Development of late-stage enantioselective hydrogenation installed the stereocenter present in the active pharmaceutical ingredient. Aspects of reagent and catalyst selection, reaction optimization, and crystallization in these two key synthetic steps are described herein.
科研通智能强力驱动
Strongly Powered by AbleSci AI