Piramal Pharma Limited

Piramal Enterprises Limited

Navnath Patil

Milind Moreshwar Gharpure

Ashutosh Jagtap

Changdev Raut

Jaisankar Krishnapillai

Nirmal Kumar Manoharan

Chirag Anilkumar Shah

Navnath Shinde

Dhileepkumar Krishnmurthy

Prashant Ladkat

Nainesh Kansagara

Kumaravel Kandasamy

The present invention provides an improved process for preparation of L-threo-(2S,3R)-3-(3,4-dihydroxyphenyl)serine (I) (Droxidopa) and its salts; comprising (a) reaction of the aldehyde compound (III) (as described herein) with Metal complex (II) (as described herein), and (h) hydrolysis of the compound (IV) obtained from step (a) in presence of acid. The present invention also relates to a novel intermediates metal chiral complex (IV) for the preparation of Droxidopa.

Process for the preparation of droxidopa and its intermediate

The present invention provides an improved process for preparation of the L-threo-(2S,3R)-3-(3 4-dihydroxyphenyl)serine (I) or a salt thereof, which is known as Droxidopa; comprising (a) recovery of the by-product compound (V) (as described herein) from the crude compound (I), and (b) recycling and re-use it for the preparation of droxidopa. Accordingly, the present invention relates to an improved economical process for the preparation of L-threo-(2S,3R)-3-(3.4-dihydroxyphenyl)serine (I) or its pharmaceutically acceptable salts; wherein the process relates to recovery and recycling of the by-product compound (V) and also to re-use it for the preparation of droxidopa.

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).

Process for the preparation of clobazam and its intermediate

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Maharashtra, India

Navnath Patil