公开(公告)号：EP3436426A1

公开(公告)日：2019-02-06

申请号：EP17773401.9

申请日：2017-03-28

申请人： Piramal Enterprises Limited

发明人： GHARPURE, Milind ,  JAGTAP, Ashutosh ,  RAUT, Changdev ,  KANSAGARA, Nainesh ,  KRISHNAPILLAI, Jaisankar ,  MANOHARAN, Nirmal Kumar ,  PATIL, Navnath

IPC分类号： C07C227/32 ,  C07C229/36 ,  C07B53/00 ,  C07F15/04 ,  C07D317/54 ,  C07C227/40

公开(公告)号：EP3274336A1

公开(公告)日：2018-01-31

申请号：EP16767830.9

申请日：2016-03-21

申请人： Piramal Enterprises Limited

发明人： JAGTAP, Ashutosh ,  GHARPURE, Milind ,  SHINDE, Navnath ,  PATIL, Navnath ,  SHAH, Chirag ,  RAUT, Changdev ,  KRISHNMURTHY, Dhileepkumar

IPC分类号： C07D243/12 ,  C07C231/02 ,  C07C233/43 ,  C07B43/06

CPC分类号： C07D243/12 ,  C07B37/10 ,  C07B2200/13 ,  C07C231/02 ,  C07C233/43

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).

公开(公告)号：EP3735403A1

公开(公告)日：2020-11-11

申请号：EP19736121.5

申请日：2019-01-03

申请人： Piramal Enterprises Limited

发明人： GHARPURE, Milind ,  JAGTAP, Ashutosh ,  RAUT, Changdev ,  PATIL, Navnath ,  LADKAT, Prashant ,  KRISHNAPILLAI, Jaisankar ,  MANOHARAN, Nirmal Kumar ,  KANDASAMY, Kumaravel

IPC分类号： C07C227/40 ,  C07C229/36 ,  C07D207/16

公开(公告)号：EP3322691A1

公开(公告)日：2018-05-23

申请号：EP16823958.0

申请日：2016-07-08

申请人： Piramal Enterprises Limited

发明人： JAGTAP, Ashutosh ,  GHARPURE, Milind ,  SHINDE, Navnath ,  PATIL, Navnath ,  RAUT, Changdev ,  KRISHNAMURTHY, Dhileepkumar

IPC分类号： C07C253/30 ,  C07C227/06 ,  C07C255/41

CPC分类号： C07C227/06 ,  C07C229/20 ,  C07C253/30 ,  C07C255/41 ,  C07C229/34

摘要： The present invention provides an improved process for the preparation of 3-(4-chlorophenyl)-3-cyanopropanoic acid (compound (A)) and further its transformation to Baclofen (I). The process comprises reaction of compound (II) with Glyoxylic acid to obtain 3-(4-chlorophenyl)-3-cyanoacrylic acid (III); followed by the ‘in-situ’ reduction of (III) in the presence of a reducing agent to provide the compound (A). Alternatively, the compound (A) is obtained by the process comprising reacting 2-(4-chlorophenyl)acetonitrile (II) with haloacetic acid (IV) in the presence of a base. The compound 3-(4-chlorophenyl)-3-cyanopropanoic acid (A) undergoes hydrogenation in the presence of a metal catalyst and ammonia solution to provide Baclofen (I).