Solid forms of 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-YL)-3,4-dihydropyrazino [2,3-b]pyrazin-2(1H)-one as tor kinase inhibitors

• US 9,975,898 B2
• Filed: 10/26/2016
• Issued: 05/22/2018
• Est. Priority Date: 04/16/2014
• Status: Active Grant

• Current Assignee: Signal Pharmaceuticals, LLC (Bristol-Myers Squibb Company)
• Original Assignee: Signal Pharmaceuticals, LLC (Bristol-Myers Squibb Company)
• Inventors: Eckert, Jeffrey
• Primary Examiner(s): Willis, Douglas M
• Application Number:
  US15/334,553
• Publication Number:
  US 20170044170A1
• Time in Patent Office: 573 Days
• Field of Search: 544350, 5462724, 5482664
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Provided herein are formulations, processes, solid forms and methods of use relating to the compound of formula (I):

• • having the name 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one and tautomers thereof.

Claims

1. A crystal form of the compound of formula (I):

2. The crystal form of claim 1, which has an X-ray powder diffraction pattern further comprising peaks at 13.54°

, 24.26° and

26.10°

±

0.2°

2θ

.

3. The crystal form of claim 1, which has a thermogravimetric analysis thermogram comprising a total mass loss of 5%±

1% of the total mass of the crystal form when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

4. The crystal form of claim 1, which has a single differential thermal analysis thermogram comprising an endotherm between 35°

C.±

5% °

C. and 105°

C.±

5% °

C. with a maximum at 89°

C.±

5% °

C. when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

5. The crystal form of claim 1, which is no less than 95% pure.

9. The crystal form of claim 1, which has a single differential thermal analysis thermogram comprising an endotherm between 35°

C.±

5% °

C. and 135°

C.±

5% °

C. with a maximum at 115°

C.±

5% °

C. when heated from 25°

C.±

5% °

C. to 300°

C. ±

5% °

C.

10. The crystal form of claim 9, wherein the single differential thermal analysis thermogram further comprises an endotherm with a maximum at 177°

C.±

5% °

C.

6. A crystal form of the compound of formula (I):

7. The crystal form of claim 6, which has an X-ray powder diffraction pattern further comprising peaks at 14.02°

, 17.46° and

24.06°

±

0.2°

2θ

.

8. The crystal form of claim 6, which has a thermogravimetric analysis thermogram comprising a total mass loss of 5.1%±

1% of the total mass of the crystal form when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

11. The crystal form of claim 6, which is no less than 95% pure.

12. A crystal form of the compound of formula (I):

13. The crystal form of claim 12, which has an X-ray powder diffraction pattern further comprising peaks at 22.74°

, 24.58° and

26.90°

±

0.2°

2θ

.

14. The crystal form of claim 12, which has a thermogravimetric analysis thermogram comprising a total mass loss of 4.2%±

1% of the total mass of the crystal form when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

15. The crystal form of claim 12, which has a single differential thermal analysis thermogram comprising an endotherm between 35°

C.±

5% °

C. and 105°

C.±

5% °

C. with a maximum at 93°

C.±

5% °

C. when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

16. The crystal form of claim 15, wherein the single differential thermal analysis thermogram further comprises an endotherm with a maximum at 178.1°

C.±

5% °

C.

17. The crystal form of claim 12, which is no less than 95% pure.

18. A crystal form of the compound of formula (I):

19. The crystal form of claim 18, which has an X-ray powder diffraction pattern further comprising peaks at 7.58°

, 12.22° and

24.22°

±

0.2°

2θ

.

20. The crystal form of claim 18, which has a thermogravimetric analysis thermogram comprising a total mass loss of 1.7%±

1% of the total mass of the crystal form when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

21. The crystal form of claim 18, which has a single differential thermal analysis thermogram comprising an endotherm between 110°

C.±

5% °

C. and 150°

C.±

5% °

C. with a maximum at 101.3°

C.±

5% °

C. when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

22. The crystal form of claim 21, wherein the single differential thermal analysis thermogram further comprises an endotherm with a maximum at 141.6°

C.±

5% °

C.

23. The crystal form of claim 18, which is no less than 95% pure.

24. A crystal form of the compound of formula (I):

25. The crystal form of claim 24, which has an X-ray powder diffraction pattern further comprising peaks at 10.82°

, 19.30° and

30.86°

±

0.2°

2θ

.

26. The crystal form of claim 24, which has a thermogravimetric analysis thermogram comprising a total mass loss of 1.6%±

1% of the total mass of the crystal form when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

27. The crystal form of claim 24, which has a single differential thermal analysis thermogram comprising an endotherm between 35°

C.±

5% °

C. and 155°

C.±

5% °

C. with a maximum at 180°

C.±

5% °

C. when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

28. The crystal form of claim 27, wherein the single differential thermal analysis thermogram further comprises an endotherm with a maximum at 236°

C.±

5% °

C.

29. The crystal form of claim 24, which is no less than 95% pure.

30. A crystal form of the compound of formula (I):

31. The crystal form of claim 30, which has an X-ray powder diffraction pattern further comprising peaks at 14.90°

, 24.18° and

26.10°

±

0.2°

2θ

.

32. The crystal form of claim 30, which has a thermogravimetric analysis thermogram comprising a total mass loss of 3.8%±

1% of the total mass of the crystal form when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

33. The crystal form of claim 30, which has a single differential thermal analysis thermogram comprising an endotherm between 35°

C.±

5% °

C. and 145°

C.±

5% °

C. with a maximum at 89°

C.±

5% °

C. when heated from 25°

C. ±

5% °

C. to 300°

C. ±

5% °

C.

34. The crystal form of claim 33, wherein the single differential thermal analysis thermogram further comprises an endotherm with a maximum at 200°

C.±

5% °

C.

35. The crystal form of claim 30, which is no less than 95% pure.

36. A crystal form of the compound of formula (I):

37. The crystal form of claim 36, which has an X-ray powder diffraction pattern further comprising peaks at 13.82°

, 19.34° and

24.26°

±

0.2°

2θ

.

38. The crystal form of claim 36, which has a thermogravimetric analysis thermogram comprising a total mass loss of 3.8%±

1% of the total mass of the crystal form when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

39. The crystal form of claim 36, which has a single differential thermal analysis thermogram comprising an endotherm between 35°

C.±

5% °

C. and 145°

C.±

5% °

C. with a maximum at 108.8°

C.±

5% °

C. when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

40. The crystal form of claim 39, wherein the single differential thermal analysis thermogram further comprises an endotherm with a maximum at 164.3°

C.±

5% °

C.

41. The crystal form of claim 36, which is no less than 95% pure.

42. A crystal form of the compound of formula (I):

43. The crystal form of claim 42, which has an X-ray powder diffraction pattern further comprising peaks at 22.18°

, 26.22° and

26.98°

±

0.2°

2θ

.

44. The crystal form of claim 42, which has a thermogravimetric analysis thermogram comprising a total mass loss of 4.2%±

1% of the total mass of the crystal form when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

45. The crystal form of claim 42, which has a single differential thermal analysis thermogram comprising an endotherm between 35°

C.±

5% °

C. and 145°

C.±

5% °

C. with a maximum at 118.7°

C.±

5% °

C. when heated from 25°

C.±

5% °

C. to 300°

C.±

5% °

C.

46. The crystal form of claim 42, which is no less than 95% pure.