过程开发
临界性
流动化学
稳健性(进化)
可扩展性
过程(计算)
工艺工程
计算机科学
工艺优化
过程控制
化学
生化工程
工程类
连续流动
化学工程
基因
操作系统
物理
数据库
生物化学
核物理学
作者
Nastaran Salehi Marzijarani,Adam J. Fine,Stephen M. Dalby,Rekha Gangam,Samiksha Poudyal,Taylor Behre,Anil R. Ekkati,Brittany M. Armstrong,C. Scott Shultz,Zachary E. X. Dance,Kevin Stone
标识
DOI:10.1021/acs.oprd.1c00231
摘要
A scalable and efficient synthesis of hydroxyindanone 3, a key intermediate for belzutifan (MK-6482), is described. Mechanistic studies revealed the sensitivity of the reduction reaction toward the CO2 byproduct. Special effort was required to design a scale-insensitive process for the removal of CO2 with active nitrogen headspace sweeping, supported by process modeling and verification with process analytical technology data. Automated sampling facilitated data-rich experimentation via kinetic profiling, culminating in enhanced understanding and further robustness-based optimization for the reduction reaction. Herein we report the development of a one-pot through-process with direct isolation of 3 in high yield (>90%) and purity (>99 LCAP, >99 ee) at commercial scales. The newly developed process ensures process robustness and improves cycle times and process mass intensity.
科研通智能强力驱动
Strongly Powered by AbleSci AI