Process for the preparation of pure and stable crystalline Raltegravir potassium form 3

Patent metadata

Field	Value
Publication number	US-10752618-B2
Application number	US-201716333613-A
Country	US
Kind code	B2
Filing date	Sep 13, 2017
Priority date	Sep 15, 2016
Publication date	Aug 25, 2020
Grant date	Aug 25, 2020

Abstract

The present invention provides improved, commercially viable and consistently reproducible processes for the preparation of pure and stable crystalline Raltegravir potassium Form 3 and pharmaceutical composition thereof.

First claim

The invention claimed is:

1. A process for the preparation of crystalline Raltegravir potassium Form 3 comprising:
(i) contacting Raltegravir in ketone or ether solvent and/or mixtures thereof, wherein the ketone is selected from acetone, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK), or mixtures thereof, and the ether solvent is selected from dimethyl ether, diethyl ether, methyl tert-butyl ether (MTBE), or mixtures thereof;
(ii) heating the reaction mass of step (i) to obtain clear solution;
(iii) adding aqueous alcoholic potassium base; and
(iv) isolating crystalline Raltegravir potassium Form 3 from the reaction mixture thereof.

2. The process of claim 1 , wherein the solvent in step (i) is selected from a mixture of acetone and methyl ethyl ketone or a mixture of acetone and methyl tert-butyl ether.

3. The process of claim 2 , wherein the solvent in step (i) is a mixture of acetone and methyl ethyl ketone.

4. The process of claim 1 , wherein step (ii) is carried out at a temperature of 30° C. to reflux temperature of solvent.

5. The process of claim 1 , wherein the potassium base employed in step (iii) is selected from potassium hydroxide, potassium ethoxide, potassium methoxide.

6. The process of claim 1 , wherein a molar ratio of the potassium base employed in step (iii) with respect to Raltegravir free acid is 0.2 to 1.2 molar equivalents.

7. The process of claim 1 , wherein the isolation in step (iv) is carried out by filtration, concentration or evaporation.

Assignees

• Lupin Ltd

Inventors

• Ray Purna Chandra
• Shabade Samir Shanteshwar
• Arora Surinder Kumar
• Lalitkumar D Rajput
• Radhakrishna B Shivdavkar
• Shantanu G Varade
• Govind D Ausekar
• Singh Girij Pal
• Deshmukh Shreyas Pandurang
• Patil Gaurav Amrut

Classifications

• C07D498/12

  in which the condensed system contains three hetero rings · CPC title

• A61K31/513

  having oxo groups directly attached to the heterocyclic ring, e.g. cytosine · CPC title

• C07D413/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title