Processes of making and crystalline forms of a MDM2 inhibitor

Patent metadata

Field	Value
Publication number	US-9623018-B2
Application number	US-201615175805-A
Country	US
Kind code	B2
Filing date	Jun 7, 2016
Priority date	Jun 10, 2013
Publication date	Apr 18, 2017
Grant date	Apr 18, 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 compound, wherein the compound is

2. A compound, wherein the compound is

3. A compound, wherein the compound is crystalline

4. The compound of claim 3 , wherein the compound is characterized by a powder X-ray diffraction pattern comprising at least three peaks at diffraction angle 2 theta degrees selected from a group consisting of peaks at approximately 8.7, 18.5, 22.6 and 26.6.

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

6. The compound of claim 3 , wherein the compound is characterized by the representative X-ray diffraction pattern shown in FIG. 3 .

7. The compound of claim 6 , wherein the compound is characterized by the X-ray diffraction pattern shown in FIG. 3 .

8. The compound of claim 4 , wherein the X-ray diffraction pattern is obtained using CuKα radiation.

9. The compound of claim 8 , wherein the X-ray diffraction pattern is obtained at room temperature.

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

11. The compound of claim 10 , wherein the X-ray diffraction pattern is obtained at room temperature.

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

13. The compound of claim 12 , wherein the X-ray diffraction pattern is obtained at room temperature.

14. The compound of claim 7 , 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 3 , wherein the compound is characterized by having a melting point of approximately 208° C.

17. The compound of claim 3 , wherein the compound is characterized by the representative differential scanning calorimetry curve shown in FIG. 10 .

18. The compound of claim 17 , wherein the compound is characterized by the differential scanning calorimetry curve shown in FIG. 10 .

19. The compound of claim 11 , wherein the compound is characterized by having a melting point of approximately 208° C.

20. The compound of claim 11 , wherein the compound is characterized by the representative differential scanning calorimetry curve shown in FIG. 10 .

21. The compound of claim 20 , wherein the compound is characterized by the differential scanning calorimetry curve shown in FIG. 10 .

22. A process of making

wherein the process comprises:
reacting

 with toluene to form

23. The process of claim 22 , wherein the process further comprises reacting

with

to form

wherein X − is CF 3 SO 3 − or

24. The process of claim 23 , wherein X is

25. The process of claim 22 , wherein the process further comprises reacting

with L-valinol followed by dehydrating conditions, and subsequently with

to form

26. The process of claim 25 , wherein the dehydrating conditions comprise reacting with triflic anhydride or p-toluenesulfonic acid anhydride in the presence of a base.

27. The process of claim 26 , wherein the base is 2,6-lutidine.

28. The process of claim 22 , wherein

is the compound of claim 3 or 11 .

Assignees

• Amgen Inc

Inventors

• Bio Matthew
• Caille Sebastien
• Fang Yuanqing
• Fox Brian M
• Lucas Brian S
• Mcgee Lawrence R
• Wiedemann Sean H

Classifications

• C07C313/02

  Sulfinic acids; Derivatives thereof · CPC title

• C07D498/04

  Ortho-condensed systems · CPC title

• A61K31/451 Primary

  having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C309/35 Primary

  Naphthalene sulfonic acids · CPC title