Industry-Oriented Route Evaluation and Process Optimization for the Preparation of Brexpiprazole | |
Chen, WM (Chen, Weiming)[ 1,2 ]; Suo, J (Suo, Jin)[ 3 ]; Liu, YJ (Liu, Yongjian)[ 4 ]; Xie, YC (Xie, Yuanchao)[ 3 ]; Wu, MJ (Wu, Mingjun)[ 4 ]; Zhu, FQ (Zhu, Fuqiang)[ 4 ]; Nian, YF (Nian, Yifeng)[ 4 ]; Aisa, HA (Aisa, Haji A.)[ 1 ]; Shen, JS (Shen, Jingshan)[ 3 ] | |
刊名 | ORGANIC PROCESS RESEARCH & DEVELOPMENT |
2019 | |
卷号 | 23期号:5页码:852-857 |
关键词 | brexpiprazole route evaluation process optimization impurity control strategy |
ISSN号 | 1083-6160 |
DOI | 10.1021/acs.oprd.8b00438 |
英文摘要 | Efforts toward route evaluation and process optimization for the preparation of brexpiprazole (1) are described. Starting from commercially available dihydroquinolinone 11, a three-step synthesis route composed of O-alkylation, oxidation, and N-alkylation was selected for industry-oriented process development aiming to reduce side reactions and achieve better impurity profiles. The reaction conditions of the three steps were investigated, and the control strategy for the process-related impurities was established. The optimized process was validated on the kilogram scale and now is viable for commercialization, with the results of not less than 99.90% purity of 1 (by HPLC) and not more than 0.05% of persistent impurities 15 and 16. |
WOS记录号 | WOS:000468697300017 |
内容类型 | 期刊论文 |
源URL | [http://ir.xjipc.cas.cn/handle/365002/7272] |
专题 | 新疆理化技术研究所_资源化学研究室 |
通讯作者 | Aisa, HA (Aisa, Haji A.)[ 1 ] |
作者单位 | 1.Topharman Shanghai Co Ltd, Bldg 1,388 Jialilue Rd,Zhangjiang Hitech Pk, Shanghai 201209, Peoples R China 2.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 4.Chinese Acad Sci, Key Lab Plant Resources & Chem Arid Reg, Xinjiang Tech Inst Phys & Chem, South Beijing Rd 40-1, Urumqi 830011, Xinjiang, Peoples R China |
推荐引用方式 GB/T 7714 | Chen, WM ,Suo, J ,Liu, YJ ,et al. Industry-Oriented Route Evaluation and Process Optimization for the Preparation of Brexpiprazole[J]. ORGANIC PROCESS RESEARCH & DEVELOPMENT,2019,23(5):852-857. |
APA | Chen, WM .,Suo, J .,Liu, YJ .,Xie, YC .,Wu, MJ .,...&Shen, JS .(2019).Industry-Oriented Route Evaluation and Process Optimization for the Preparation of Brexpiprazole.ORGANIC PROCESS RESEARCH & DEVELOPMENT,23(5),852-857. |
MLA | Chen, WM ,et al."Industry-Oriented Route Evaluation and Process Optimization for the Preparation of Brexpiprazole".ORGANIC PROCESS RESEARCH & DEVELOPMENT 23.5(2019):852-857. |
个性服务 |
查看访问统计 |
相关权益政策 |
暂无数据 |
收藏/分享 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论