Processes of making and crystalline forms of a MDM2 inhibitor

Patent metadata

Field	Value
Publication number	US-9801867-B2
Application number	US-201615175824-A
Country	US
Kind code	B2
Filing date	Jun 7, 2016
Priority date	Jun 10, 2013
Publication date	Oct 31, 2017
Grant date	Oct 31, 2017

Abstract

The present invention provides processes for making 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid as well as intermediates and processes for making the intermediates. Also provided are crystalline forms of the compound and the intermediates.

First claim

What is claimed is:

1. A process of making

the process comprising reacting

to form

2. The process of claim 1 , wherein the process further comprises preparing a mixture of

and toluene.

3. The process of claim 1 , wherein the process further comprises preparing a mixture of

and toluene.

4. The process of claim 3 , wherein

which is used to prepare the mixture, is a crystalline compound.

5. The process of claim 4 , wherein the crystalline compound is characterized by a powder X-ray diffraction pattern comprising peaks at a diffraction angle 2 theta degrees at approximately 8.7, 18.5, 22.6 and 26.6.

6. The process of claim 5 , wherein the X-ray diffraction pattern is obtained using CuKα radiation.

7. The process of claim 6 , wherein the X-ray diffraction pattern is obtained at room temperature.

8. A process of making

the process comprising reacting

with 1,4-diazabicyclo[2.2.2]octane (DABCO) to form

9. The process of claim 8 , wherein the process further comprises reacting

under oxidizing conditions to form

10. The process of claim 9 , wherein the oxidizing conditions comprise a reaction with ozone followed by a Pinnick oxidation.

11. The process of claim 8 , wherein

is a compound characterized by a powder X-ray diffraction pattern comprising at least three peaks at a diffraction angle 2 theta degrees selected from a group consisting of peaks at approximately 11.5, 14.3, 15.8, 17.7, 19.5 and 20.7.

12. The process of claim 11 , wherein

is a compound characterized by a powder X-ray diffraction pattern comprising at least five peaks at diffraction angle 2 theta degrees selected from a group consisting of peaks at approximately 11.5, 14.3, 15.8, 17.7, 19.5 and 20.7.

13. The process of claim 8 , wherein

is a compound characterized by a powder X-ray diffraction pattern comprising peaks at diffraction angle 2 theta degrees at approximately 11.5, 14.3, 15.8, 17.7, 19.5 and 20.7.

14. The compound of claim 11 , wherein the X-ray diffraction pattern is obtained using CuKα radiation.

15. The compound of claim 14 , wherein the X-ray diffraction pattern is obtained at room temperature.

16. The compound of claim 12 , wherein the X-ray diffraction pattern is obtained using CuKα radiation.

17. The compound of claim 16 , wherein the X-ray diffraction pattern is obtained at room temperature.

18. The compound of claim 13 , wherein the X-ray diffraction pattern is obtained using CuKα radiation.

19. The compound of claim 18 , wherein the X-ray diffraction pattern is obtained at room temperature.

20. A process of making

the process comprising reacting

with an acid to form

21. The process of claim 20 , wherein the acid is hydrochloric acid.

22. The process of claim 20 , wherein

is a compound characterized by a powder X-ray diffraction pattern comprising at least three peaks at a diffraction angle 2 theta degrees selected from a group consisting of peaks at approximately 8.4, 11.6, 12.4, 18.6, 19.0, 23.6, and 30.4.

23. The process of claim 22 , wherein

is a compound characterized by a powder X-ray diffraction pattern comprising at least five peaks at diffraction angle 2 theta degrees selected from a group consisting of peaks at approximately 8.4, 11.6, 12.4, 18.6, 19.0, 23.6, and 30.4.

24. The process of claim 20 , wherein

is a compound characterized by a powder X-ray diffraction pattern comprising peaks at diffraction angle 2 theta degrees at approximately 8.4, 11.6, 12.4, 18.6, 19.0, 23.6, and 30.4.

25. The compound of claim 22 , wherein the X-ray diffraction pattern is obtained using CuKα radiation.

26. The compound of claim 25 , wherein the X-ray diffraction pattern is obtained at room temperature.

27. The compound of claim 23 , wherein the X-ray diffraction pattern is obtained using CuKα radiation.

28. The compound of claim 27 , wherein the X-ray diffraction pattern is obtained at room temperature.

29. The compound of claim 24 , wherein the X-ray diffraction pattern is obtained using CuKα radiation.

30. The compound of claim 29 , wherein the X-ray diffraction pattern is obtained at room temperature.

Assignees

• Amgen Inc

Inventors

• Bio Matthew
• Caille Sebastien
• Cochran Brian
• Fang Yuanqing
• Fox Brian M
• Lucas Brian S
• Mcgee Lawrence R
• Vounatsos Filisaty
• Wiedemann Sean H
• Wortman Sarah

Classifications

• C07D498/04

  Ortho-condensed systems · CPC title

• C07C309/25

  having sulfo groups bound to carbon atoms of rings other than six-membered aromatic rings of a carbon skeleton · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C313/02

  Sulfinic acids; Derivatives thereof · CPC title

• C07D491/048

  the oxygen-containing ring being five-membered · CPC title