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A Process For The Preparation Of Brivaracetam From (S) 3 (2 (Chloroamino) 2 Oxoethyl) Hexanoic Acid”

Abstract: " A Process for Preparing Brivaracetam" A process for the preparation of Brivaracetam, an anti-convulsion drug, is provided comprising Hofmann rearrangement of (S)-3-(2-(chloroamino)-2-oxoethyl) hexanoic acid, followed by cyclization resulting in (R)-4-propyl-pyrrolidin-2-one which on condensation with bromo butyric acid or ester followed by reaction with ammonia results in Brivaracetam.

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Notices, Deadlines & Correspondence

Patent Information

Application #
Filing Date
21 October 2019
Publication Number
44/2019
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
Parent Application
Patent Number
Legal Status
Grant Date
2020-12-28
Renewal Date

Applicants

DIVI'S LABORATORIES LTD
1-71-72/23(P)/DIVIS/303, DIVI TOWERS, CYBER HILLS, GACHIBOWLI, HYDERABAD-500032, TELANGANA, INDIA.

Inventors

1. MURALI KRISHNA PRASAD DIVI
1-71-72/23(P)/DIVIS/303, DIVI TOWERS, CYBER HILLS, GACHIBOWLI, HYDERABAD-500032, TELANGANA, INDIA.
2. MYSORE ASWATHA NARAYANA RAO
1-71-72/23(P)/DIVIS/303, DIVI TOWERS, CYBER HILLS, GACHIBOWLI, HYDERABAD-500032, TELANGANA, INDIA.
3. SHAIK NOWSHUDDIN
1-71-72/23(P)/DIVIS/303, DIVI TOWERS, CYBER HILLS, GACHIBOWLI, HYDERABAD-500032, TELANGANA, INDIA.

Specification

1. A process for the preparation of brivaracetam having the structure:
Di Lvamuemm comprising :
a) reacting (S)-3-(2-amino-2-oxoethyl) hcxanoic acid having the staicture (II):
with a chlorinating agent selected from the group consisting of trichloroisocyanuric acid, sodium dichloroisocyanurate and N-chtorosuccinimide, in a solvent selected from the group consisting of methanol, ethanol, acetonitrile, and dimethyl formamide at a temperature between 20° C and 40°C to produce (S)-3-(2-(chloroamino)-2-oxoethyl) hexanoic acid having the structure (III):

b) reacting (III) with sodium hydroxide in water, initially at a temperature between 15° C and 30°C, and later at a temperature between 85° C and 95° C to produce (R)-4-propyl-pyrrolidin-2-one having the structure (1)
(I) or optionally, the compound (III) is reacted with sodium hydroxide at a temperature between 15° C and 30°C to obtain (R)-3-(aminomethyl) hexanoic acid having the structure (IV)
followed by cyclizing the compound (IV) at a temperature between 85° C and 95° C to form (R)-4-propyl-pyrrolidin-2-one (I)
c) converting the reaction product of step (b) or (c) into brivaracetam.
2. A compound (S)-3-(2-(chloroamino)-2-oxoethyl) hexanoic acid having the structure (III)
3. The process as claimed in claim la, wherein the (S)-3-(2-amino-2-oxoethyl) hexanoic acid (II) is prepared by:
a) reacting 4-propyl piperidine-2,6-dione having the structure (V)

with an aqueous solution of sodium hydroxide at a temperature between 40° C and 60° C to obtain a racemic mixture of 3-(2-amino-2-oxoethyl) hexanoic acid having the structure (VI):
b) reacting racemic (VI) with (S)-(-)-l-PhenyIethylamine in chloroform containing (
2 to 5 % ethanol at a temperature between 40° C and 55° C followed by cooling to
obtain (S)-3-(2-amino-2-oxoethyl) hexanoic acid (II) as a salt of (S)-(-)-l-Phenylethylamine; and
c) hydrolyzing the precipitated salt to obtain (S)-3-(2-amino-2-oxoethyl) hexanoic
acid (II).
4. A process as claimed in claim 1, wherein the isomer, (R)-3-(2-amino-2-oxoethyl) hexanoic acid having the structure (Ha), remaining after obtaining (S)-3-(2-amino-2-oxoethyl) hexanoic acid (II) from the racemic mixture as per the reaction of claim 5 stage (b),

is heated in toluene in the presence of a catalyst selected from the group consisting of boron trioxide, para-toluenesulfonic acid and sulfuric acid at a temperature between 100°C and 110° C to obtain4-propyl piperidine-2,6-dione (V).

Documents

Application Documents

# Name Date
1 Form2 Title Page_Complete_21-10-2019.pdf 2019-10-21
2 Form 1_As Filed_21-10-2019.pdf 2019-10-21
3 Description Complete_As Filed_21-10-2019.pdf 2019-10-21
4 Correspondence by Applicant _As Filed_21-10-2019.pdf 2019-10-21
5 Claims_As Filed_21-10-2019.pdf 2019-10-21
6 Abstract_As Filed_21-10-2019.pdf 2019-10-21
7 Form9_Earlier Publication_28-10-2019.pdf 2019-10-28
8 Form18_Normal Request_28-10-2019.pdf 2019-10-28
9 Form 5_After Provisional_28-10-2019.pdf 2019-10-28
10 Correspondence by Applicant _Form 9_28-10-2019.pdf 2019-10-28
11 Correspondence by Applicant _Form 18_28-10-2019.pdf 2019-10-28
12 Form3_As Filed_21-11-2019.pdf 2019-11-21
13 Correspondence by Applicant_Form-3_21-11-2019.pdf 2019-11-21
14 201941042636-Marked Copy-FER Reply-04-11-2020.pdf 2020-11-04
15 201941042636-Form 3-FER Reply-04-11-2020.pdf 2020-11-04
16 201941042636-Form 2 Title Page_Complete-04-11-2020.pdf 2020-11-04
17 201941042636-Form 1-FER Reply-04-11-2020.pdf 2020-11-04
18 201941042636-Correspondence-FER Reply-04-11-2020.pdf 2020-11-04
19 201941042636-Claims-FER Reply-04-11-2020.pdf 2020-11-04
20 201941042636-Amended Pages Of Specification-FER Reply-04-11-2020.pdf 2020-11-04
21 201941042636-Abstract-FER Reply-04-11-2020.pdf 2020-11-04
22 201941042636-PatentCertificate28-12-2020.pdf 2020-12-28
23 201941042636-IntimationOfGrant28-12-2020.pdf 2020-12-28
24 201941042636-Renewal Fee_26-07-2021.pdf 2021-07-26
25 201941042636-FER.pdf 2021-10-17
26 201941042636-Correspondence_Renewal Fee_08-08-2022.pdf 2022-08-08
27 201941042636-Renewal 7 th Year .pdf 2025-07-18

Search Strategy

1 2020_0029_TranscriptC_29-09-2020.pdf
2 201941042636searchreportE_24-07-2020.pdf

ERegister / Renewals

3rd: 26 Jul 2021

From 21/10/2021 - To 21/10/2022

4th: 08 Aug 2022

From 21/10/2022 - To 21/10/2023

5th: 23 Aug 2023

From 21/10/2023 - To 21/10/2024

6th: 22 Jul 2024

From 21/10/2024 - To 21/10/2025

7th: 17 Jul 2025

From 21/10/2025 - To 21/10/2026