Processes of making and crystalline forms of a MDM2 inhibitor

Patent metadata

Field	Value
Publication number	US-9376386-B2
Application number	US-201414301087-A
Country	US
Kind code	B2
Filing date	Jun 10, 2014
Priority date	Jun 10, 2013
Publication date	Jun 28, 2016
Grant date	Jun 28, 2016

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 crystalline anhydrous

characterized by a powder X-ray diffraction pattern comprising peaks at diffraction angle 2 theta degrees at approximately 11.6, 12.4, 18.6, 19.0, 21.6 and 23.6.

2. The compound of claim 1 , wherein the compound is characterized by the representative X-ray diffraction pattern shown in FIG. 1 .

3. The compound of claim 1 , wherein the compound is characterized by the X-ray diffraction pattern shown in FIG. 1 .

4. The compound of claim 1 , wherein the X-ray diffraction pattern is obtained using CuKα radiation.

5. The compound of claim 4 , wherein the X-ray diffraction pattern is obtained at room temperature.

6. The compound of claim 1 , wherein the compound is characterized by having a melting point of approximately 161° C.

7. The compound of claim 1 , wherein the compound is characterized by the representative differential scanning calorimetry curve shown in FIG. 8 .

8. The compound of claim 1 , wherein the compound is characterized by the differential scanning calorimetry curve shown in FIG. 8 .

9. A pharmaceutical composition comprising the compound of any one of claims 1 - 8 and a pharmaceutically acceptable excipient.

10. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is a solid dosage form.

11. The pharmaceutical composition of claim 10 , wherein the solid dosage form is a capsule, tablet, powder, or granule.

12. The pharmaceutical composition of claim 11 , wherein the solid dosage form is a tablet.

13. The pharmaceutical composition of any one of claims 10 - 12 , wherein the solid dosage form is for oral administration.

14. A compound, wherein the compound is crystalline

ethanolate
characterized by a powder X-ray diffraction pattern comprising peaks at diffraction angle 2 theta degrees at approximately 10.5, 18.2, 20.3, 21, 21.9 and 24.2.

15. The compound of claim 14 , wherein the compound is characterized by the representative X-ray diffraction pattern shown in FIG. 6 .

16. The compound of claim 14 , wherein the compound is characterized by the X-ray diffraction pattern shown in FIG. 6 .

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

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

19. The compound of claim 14 , wherein the compound is characterized by having a melting point of approximately 90° C.

20. The compound of claim 14 , wherein the compound is characterized by the representative differential scanning calorimetry curve shown in FIG. 11 .

21. The compound of claim 14 , wherein the compound is characterized by the differential scanning calorimetry curve shown in FIG. 11 .

22. A compound, wherein the compound is crystalline

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.

23. The compound of claim 22 , wherein the compound is characterized by the representative X-ray diffraction pattern shown in FIG. 12 .

24. The compound of claim 22 , wherein the compound is characterized by the X-ray diffraction pattern shown in FIG. 12 .

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 22 , wherein the compound is characterized by having a melting point of approximately 96° C.

28. The compound of claim 22 , wherein the compound is characterized by the representative differential scanning calorimetry curve shown in FIG. 13 .

29. The compound of claim 22 , wherein the compound is characterized by the differential scanning calorimetry curve shown in FIG. 13 .

30. A compound, wherein the compound is crystalline

of Form 1
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 10.7, 11.2, 19.0, 21.5 and 23.0.

31. The compound of claim 30 , wherein the compound is characterized by a powder X-ray diffraction pattern comprising at least four peaks at diffraction angle 2 theta degrees selected from the group.

32. The compound of claim 30 , wherein the compound is characterized by a powder X-ray diffraction pattern comprising peaks at diffraction angle 2 theta degrees at approximately 10.7, 11.2, 19.0, 21.5 and 23.0.

33. The compound of claim 30 , wherein the compound is characterized by the representative X-ray diffraction pattern shown in FIG. 4 .

34. The compound of claim 30 , wherein the compound is characterized by the X-ray diffraction pattern shown in FIG. 4 .

35. The compound of claim 30 , wherein the X-ray diffraction pattern is obtained using CuKα radiation.

36. The compound of claim 35 , wherein the X-ray diffraction pattern is obtained at room temperature.

37. A compound, wherein the compound is crystalline

of Form 2
characterized by a powder X-ray diffraction pattern comprising peaks at diffraction angle 2 theta degrees at approximately 12.9, 20.2 and 28.7.

38. The compound of claim 37 , wherein the compound is characterized by the representative X-ray diffraction pattern shown in FIG. 5 .

39. The compound of claim 37 , wherein the compound is characterized by the X-ray diffraction pattern shown in FIG. 5 .

40. The compound of claim 37 , wherein the X-ray diffraction pattern is obtained using CuKα radiation.

41. The compound of claim 40 , wherein the X-ray diffraction pattern is obtained at room temperature.

42. A compound, wherein the compound is crystalline

propanol solvate
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 9.0, 10.3, 12.7, 15.7, 17.9, 20.1 and 20.8.

43. The compound of claim 42 , wherein the compound is characterized by a powder X-ray diffraction pattern comprising at least five peaks at diffraction angle 2 theta degrees selected from the group.

44. The compound of claim 42 , wherein the compound is characterized by a powder X-ray diffraction pattern comprising peaks at diffraction angle 2 theta degrees at approximately 9.0, 10.3, 12.7, 15.7, 17.9, 20.1 and 20.8.

4

Assignees

• Amgen Inc
• Amgen Inc

Inventors

• Bio Matthew
• Caille Sebastien
• Cochran Brian
• Fang Yuanqing
• Vounatsos Filisaty
• Wortman Sarah

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C309/04

  containing only one sulfo group · CPC title

• C07D211/76 Primary

  attached in position 2 or 6 · CPC title

• C07D211/94 Primary

  Oxygen atom, e.g. piperidine N-oxide · CPC title

• C07D491/048

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