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“Improved Process For The Preparation Of 1 Methyl 2 (2,6 Xylyloxy) Ethylamine Hydrochloride (Mexiletine Hydrochloride)”

Abstract: The present invention relates to an improved process for the preparation of substantially pure Mexiletine hydrochloride (1) with purity greater than 99.0 %.

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Patent Information

Application #
Filing Date
28 June 2019
Publication Number
01/2021
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
radha@biophore.com
Parent Application
Patent Number
Legal Status
Grant Date
2025-02-17
Renewal Date

Applicants

Biophore India pharmaceuticals Pvt. Ltd
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.

Inventors

1. Manik Reddy Pullagurla
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.
2. Bhaskar Reddy Pitta
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.
3. Jagadeesh Babu Rangisetty
Plot#92; 1-98/2/92, Kavuri Hills – Phase II, Jubilee Hills, Hyderabad, Telangana India-500033.

Specification

We claim:
1. A process for the preparation of Mexiletine hydrochloride (1) having purity
greater than 99.0 % by HPLC comprising:
a) acylating 2,6-dimethylphenol (5) with chloroacetone in the presence of an aprotic solvent and a base to obtain l-(2,6-dimethylphenoxy) propan-2-one (4);
b) reacting l-(2,6-dimethylphenoxy)propan-2-one (4) with hydroxylamine hydrochloride in the presence of a protic solvent to obtain l-(2',6'-dimethylphenoxy)-2-propane oxime (3);
c) reducing l-(2',6'-dimethylphenoxy)-2-propane oxime with hydrogen gas in the presence of a metal reducing agent in alcohol to obtain l-(2',6'-dimethylphenoxy)-2-amino-propane (2) (Mexiletine base); and
d) treating Mexiletine base (2) with isopropyl alcoholic hydrochloric acid in an aprotic solvent to obtain Mexiletine hydrochloride (1).

2. The process according to claim 1, wherein the aprotic solvent used in step a) can be selected from tetrahydrofuran, dichloromethane, ethyl acetate, acetone, dichloromethane.
3. The process according to claim 1, wherein the base used in step a) can be selected from sodium hydride, triethylamine, N,N-diisopropylethyl amine, 4-dimethylamino pyridine, sodium carbonate, potassium carbonate.
4. The process according to claim 1, wherein the protic solvent used in step b) can be selected from methanol, ethanol, isopropanol, water.
5. The process according to claim 1, wherein the metal reducing agent used in step c) can be selected from palladium on carbon, Raney nickel, platinum.

6. The process according to claim 1, wherein the aprotic solvent used in step d) can be selected from tetrahydrofuran, dichloromethane, ethyl acetate, acetone, dichloromethane.
7. A process for the purification of Mexiletine hydrochloride (1), comprising:

f) providing a solution of Mexiletine hydrochloride (1) in a protic solvent;
g) stirring the reaction mixture and filtering;

h) distilling off the solvent under vacuum and adding an aprotic solvent; i) filtering the reaction mixture and washing with an aprotic solvent; and j) isolating pure Mexiletine hydrochloride (1).
8. The process according to claim 7, wherein the protic solvents used can be selected from methanol, ethanol, isopropanol, water and the aprotic solvents used can be selected from ethyl acetate, methyl tertiary butyl ether, acetone, dichloromethane.
9. The process according to claim 7, wherein the Mexiletine hydrochloride (1) is having purity greater than 99.0 % and one or more of the following:

a) less than 0.15 % of impurity A;
b) less than 0.15% of impurity C; and
c) less than 0.15% of impurity D.

Documents

Application Documents

# Name Date
1 201941025908-IntimationOfGrant17-02-2025.pdf 2025-02-17
1 201941025908-PROVISIONAL SPECIFICATION [28-06-2019(online)].pdf 2019-06-28
2 201941025908-FORM 1 [28-06-2019(online)].pdf 2019-06-28
2 201941025908-PatentCertificate17-02-2025.pdf 2025-02-17
3 201941025908-DRAWINGS [28-06-2019(online)].pdf 2019-06-28
3 201941025908-ABSTRACT [12-02-2025(online)].pdf 2025-02-12
4 Form 1_After Filing_15-07-2019.pdf 2019-07-15
4 201941025908-CLAIMS [12-02-2025(online)].pdf 2025-02-12
5 Correspondence by Applicant_Form 1_15-07-2019.pdf 2019-07-15
5 201941025908-FER_SER_REPLY [12-02-2025(online)].pdf 2025-02-12
6 201941025908-FORM 3 [27-06-2020(online)].pdf 2020-06-27
6 201941025908-FER.pdf 2024-08-12
7 201941025908-FORM 18 [08-06-2023(online)].pdf 2023-06-08
7 201941025908-ENDORSEMENT BY INVENTORS [27-06-2020(online)].pdf 2020-06-27
8 201941025908-Correspondence_Form2-Form3-Form5 and Specification_03-09-2020.pdf 2020-09-03
8 201941025908-DRAWING [27-06-2020(online)].pdf 2020-06-27
9 201941025908-COMPLETE SPECIFICATION [27-06-2020(online)].pdf 2020-06-27
10 201941025908-DRAWING [27-06-2020(online)].pdf 2020-06-27
10 201941025908-Correspondence_Form2-Form3-Form5 and Specification_03-09-2020.pdf 2020-09-03
11 201941025908-FORM 18 [08-06-2023(online)].pdf 2023-06-08
11 201941025908-ENDORSEMENT BY INVENTORS [27-06-2020(online)].pdf 2020-06-27
12 201941025908-FORM 3 [27-06-2020(online)].pdf 2020-06-27
12 201941025908-FER.pdf 2024-08-12
13 Correspondence by Applicant_Form 1_15-07-2019.pdf 2019-07-15
13 201941025908-FER_SER_REPLY [12-02-2025(online)].pdf 2025-02-12
14 Form 1_After Filing_15-07-2019.pdf 2019-07-15
14 201941025908-CLAIMS [12-02-2025(online)].pdf 2025-02-12
15 201941025908-DRAWINGS [28-06-2019(online)].pdf 2019-06-28
15 201941025908-ABSTRACT [12-02-2025(online)].pdf 2025-02-12
16 201941025908-PatentCertificate17-02-2025.pdf 2025-02-17
16 201941025908-FORM 1 [28-06-2019(online)].pdf 2019-06-28
17 201941025908-PROVISIONAL SPECIFICATION [28-06-2019(online)].pdf 2019-06-28
17 201941025908-IntimationOfGrant17-02-2025.pdf 2025-02-17

Search Strategy

1 201941025908_SearchE_03-07-2024.pdf

ERegister / Renewals

3rd: 19 May 2025

From 28/06/2021 - To 28/06/2022

4th: 19 May 2025

From 28/06/2022 - To 28/06/2023

5th: 19 May 2025

From 28/06/2023 - To 28/06/2024

6th: 19 May 2025

From 28/06/2024 - To 28/06/2025