胺化
亲核芳香族取代
亲核取代
化学
流动化学
替代(逻辑)
取代反应
还原胺化
组合化学
药物化学
有机化学
计算化学
计算机科学
催化作用
程序设计语言
作者
Junu Kim,Yusuke Hayashi,Sara Badr,Kazuya Okamoto,Toshikazu Hakogi,Haruo Furukawa,Satoshi Yoshikawa,Hayao Nakanishi,Hirokazu Sugiyama
标识
DOI:10.1021/acs.oprd.3c00380
摘要
A kinetic study and model-based design space determination for drug substance flow synthesis using an amination reaction are presented. A flow experiment was conducted to synthesize 3-fluoro-4-morpholinobenzonitrile from 3,4-difluorobenzonitrile, morpholine, and diazabicycloundecene. Concentrations, residence time, temperature, and reactor inner diameter were varied to gather the kinetic data. A set of equations was defined to describe the mass and energy balances, and the developed model could reproduce the experimental profiles with high accuracy. By incorporating the Reynolds number into the pre-exponential factor, the developed one-dimensional model could account for performance variations in different inner diameter conditions. The model was then used to identify the design space, considering yield, temperature, productivity, and environment. The study also evaluated the process robustness given pulse disturbances, which could help identify the required sensor monitoring. Finally, a method for facilitating regulatory processes was proposed. The presented model-based approach can aid in producing high-quality pharmaceuticals in an efficient, sustainable, and cost-effective way by utilizing digital power.
科研通智能强力驱动
Strongly Powered by AbleSci AI