Process for preparation of darunavir

Patent metadata

Field	Value
Publication number	US-2019144461-A1
Application number	US-201916244900-A
Country	US
Kind code	A1
Filing date	Jan 10, 2019
Priority date	Jul 24, 2012
Publication date	May 16, 2019
Grant date	—

Abstract

The present invention provides a process for the preparation of darunavir or solvates or a pharmaceutically acceptable salt thereof substantially free of bisfuranyl impurities, particularly darunavir propionate solvate. The present invention also provides a process for preparation amorphous darunavir using the darunavir propionate solvate.

First claim

1 - 12 . (canceled)

13 . Darunavir propionate solvate.

14 . The darunavir propionate solvate of claim 13 characterized by an X-Ray diffraction (XRD) pattern substantially in accordance with FIG. 1 .

15 - 49 . (canceled)

50 . The darunavir propionate solvate of claim 14 having a chemical purity of greater than about 99.5% as measured by HPLC.

51 . The darunavir propionate solvate of claim 14 having less than about 0.1% by HPLC of one or more of its diastereomer impurities,

52 . Darunavir propionate solvate of claim 14 substantially free of one or more of the impurities,

53 . The method according to claim 54 , further comprising forming a pharmaceutical composition by combining the precipitated solid darunavir propionate solvate or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

54 . A method for the preparation of darunavir propionate solvate according to claim 14 comprising:
a) mixing an amount of 1-([[(3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yloxy]-carbonyl]oxy)-2,5-pyrrolidinedione of Formula V, ethyl acetate, and water in a mixing vessel,

b) adding to the reaction mass of step a) an amount of the compound of Formula II at 25° C. to 30° C.,

c) adding to the reaction mass of step b) an amount of aqueous potassium carbonate;
d) separating the organic layer thus formed and washing the same with an amount of water;
e) distilling from the organic layer obtained in step d) the ethyl acetate under vacuum to obtain a residue;
f) mixing an amount of propionic acid with the residue obtained from step e) at 25° C. to 30° C. to form the darunavir propionate solvate;
g) precipitating the darunavir propionate solvate from the mixture of step f) and dry the same under reduced pressure to obtain a solid.

Assignees

• Laurus Labs Ltd

Inventors

• Chivukula Kameswar R
• Murthy Venkata R
• Indukuri Venkata S
• Goranta Seeta R

Classifications

• A61P31/18

  for HIV · CPC title

• C07C303/38

  by reaction of ammonia or amines with sulfonic acids, or with esters, anhydrides, or halides thereof · CPC title

• C07D493/04 Primary

  Ortho-condensed systems · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title