发明公开
EP3274336A1 AN IMPROVED PROCESS FOR THE PREPARATION OF CLOBAZAM AND ITS INTERMEDIATE
审中-公开
一种改进的CLOBAZAM制剂及其中间体工艺
- 专利标题: AN IMPROVED PROCESS FOR THE PREPARATION OF CLOBAZAM AND ITS INTERMEDIATE
- 专利标题(中): 一种改进的CLOBAZAM制剂及其中间体工艺
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申请号: EP16767830.9申请日: 2016-03-21
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公开(公告)号: EP3274336A1公开(公告)日: 2018-01-31
- 发明人: JAGTAP, Ashutosh , GHARPURE, Milind , SHINDE, Navnath , PATIL, Navnath , SHAH, Chirag , RAUT, Changdev , KRISHNMURTHY, Dhileepkumar
- 申请人: Piramal Enterprises Limited
- 申请人地址: Piramal Tower Ganpatrao Kadam Marg Lower Parel Mumbai 400 013 IN
- 专利权人: Piramal Enterprises Limited
- 当前专利权人: Piramal Enterprises Limited
- 当前专利权人地址: Piramal Tower Ganpatrao Kadam Marg Lower Parel Mumbai 400 013 IN
- 代理机构: Richards, Michèle E.
- 优先权: IN966MU2015 20150324
- 国际公布: WO2016151464 20160929
- 主分类号: C07D243/12
- IPC分类号: C07D243/12 ; C07C231/02 ; C07C233/43 ; C07B43/06
摘要:
The present invention provides an improved process for the preparation of 8-chloro-1-phenyl-1H-benzo[b][1,4]diazepine-2,4(3H,5H)-dione (hereafter referred to as the compound (IV)), which is useful as a key intermediate for the synthesis of Clobazam (referred to as the compound (I)) 7-chloro-1-methyl-5-phenyl-1H-benzo[b][1,4]diazepine-2,4(3H,5H)-dione. The process of the present invention further involves transformation of the compound (IV) into Clobazam (I), comprising (a) reacting the compound (II) (as described herein) with monoalkyl malonate in the presence of a coupling agent to obtain the compound (III) (as described herein); followed by the cyclization using a base; (b) reacting the compound-IV (as described herein) obtained from step (a) with methylating agent. The process of the present invention involves formation of novel intermediates methyl 3-((4-chloro-2-(phenylamino)phenyl)amino)-3-oxopropanoate (IIIa) and 3-((4-chloro-2-(phenylamino)phenyl)amino)-3-oxopropanoic acid (V).
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