Process for preparing atazanavir sulphate

Patent metadata

Field	Value
Publication number	US-9890121-B2
Application number	US-201414767054-A
Country	US
Kind code	B2
Filing date	Feb 12, 2014
Priority date	Feb 12, 2013
Publication date	Feb 13, 2018
Grant date	Feb 13, 2018

Abstract

The present invention relates to a process for the preparation of Compound (A):

wherein the process comprises contacting atazanavir base (Compound (II))

with sulphuric acid in a combination of two or more solvents and isolating compound (A). The present invention also relates to substantially pure Compound (A), and to Compound (A) devoid of mesityl oxide impurity. Mesityl oxide has the following formula:

First claim

The invention claimed is:

1. A process for the preparation of Compound (A):

wherein the process comprises i) suspending atazanavir base (Compound (II))

in a combination of two or more solvents, ii) contacting the suspension of Compound (II) and two or more solvents with sulphuric acid, and iii) isolating Compound (A) wherein the combination of two or more solvents comprises a first solvent which comprises a water immiscible, or moderately soluble in water, solvent that is selected from the group consisting of: ethyl acetate, isopropyl acetate, and isobutyl acetate, and a second solvent which comprises a water miscible solvent that is selected from the group consisting of: alcohol, dimethylsulfoxide, and dimethylformamide and wherein the ratio of first solvent to second solvent is in the range of 10:3 to 10:1.

2. The process according to claim 1 , wherein to second solvent is 10:1.

3. The process according to claim 1 , wherein the combination of two or more solvents comprises more than two solvents.

4. The process according to claim 1 , wherein the combination of solvents is selected from the following group:
a) ethyl acetate-methanol;
b) ethyl acetate-dimethylsulfoxide;
c) ethyl acetate-dimethylformamide;
d) isopropyl acetate-methanol;
e) isopropyl acetate-dimethylsulfoxide; and
f) isopropyl acetate-dimethylformamide.

5. The process according to claim 4 , wherein the combination of solvents is ethyl acetate-methanol.

6. The process according to claim 1 , wherein the sulphuric acid is added at a temperature ranging from 35° C. to 60° C.

7. The process according to claim 1 , wherein the sulphuric acid is added at a temperature of 43±2° C.

8. The process according to claim 1 , wherein the Compound (A) is isolated by filtration.

9. The process according to claim 8 , wherein prior to isolation by filtration, Compound (A) precipitates and the precipitated solid is mixed with a water immiscible solvent.

10. The process according to claim 9 , wherein the solid is mixed with ethyl acetate.

11. The process according to claim 1 , wherein Compound (A) isolated in step iii has 0.2% by weight of total impurities or less.

12. The process according to claim 11 , wherein Compound (A) has 0.1% by weight of total impurities or less.

13. The process according to claim 11 , wherein Compound (A) is devoid of mesityl oxide impurity:

14. The process according to claim 11 further comprising combining Compound (A), together with one or more pharmaceutically acceptable excipients to produce a pharmaceutical composition.

15. The process according to claim 14 , wherein the Compound (A) is present in the pharmaceutical composition in combination with another active pharmaceutical ingredient.

16. The process according to claim 9 wherein after filtration the solid is washed with ethyl acetate.

17. The process according to claim 16 , wherein after washing the solid is dried under vacuum at 27±2° C. for 2 hours.

18. The process according to claim 17 , wherein after drying the solid is powdered and dried again under vacuum at 53±2° C. for 4 hours.

Assignees

• Cipla Ltd

Inventors

• Kankan Rajendra Narayanrao
• Pathi Srinivas Laxminarayan
• Chinimilli Venugopalarao

Classifications

• C07D213/42

  having hetero atoms attached to the substituent nitrogen atom (nitro radicals C07D213/26) · CPC title

• C07D213/58 Primary

  Amidines · CPC title