期刊
ORGANIC PROCESS RESEARCH & DEVELOPMENT
卷 23, 期 5, 页码 858-869出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.oprd.8b00441
关键词
merestinib; continuous processing; small volume continuous; continuous crystallization; flow chemistry
Development of a small volume continuous process that used a combination of batch and flow unit operations to manufacture the small molecule oncolytic candidate merestinib is described. Continuous processing was enabled following the identification and development of suitable chemical transformations and unit operations. Aspects of the nascent process control strategy were evaluated in the context of a 20 kg laboratory demonstration campaign, executed in walk-in fume hoods at a throughput of 5-10 kg of active pharmaceutical ingredient per day. The process comprised an automated Suzuki-Miyaura cross-coupling reaction, a nitro-group hydrogenolysis, a continuous amide bond formation, and a continuous deprotection. Three of the four steps were purified using mixed-suspension, mixed-product removal crystallizations. Process analytical technology enabled real-time or nearly real-time process diagnostics. Findings from the demonstration campaign informed a second process development cycle as well as decision making for what steps to implement using continuous processing in a proximate manufacturing campaign, which will be described in part 2 of this series.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据