Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-alpha]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof

Patent metadata

Field	Value
Publication number	US-9951080-B2
Application number	US-201715803538-A
Country	US
Kind code	B2
Filing date	Nov 3, 2017
Priority date	Oct 16, 2015
Publication date	Apr 24, 2018
Grant date	Apr 24, 2018

Abstract

The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis), kits, methods of synthesis, and products-by-process.

First claim

I claim:

1. A crystalline hemihydrate of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

2. The crystalline hemihydrate of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 13.4±0.2, 15.1±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.

3. The crystalline hemihydrate of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 13.4±0.2, 15.1±0.2, 17.0±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.

4. The crystalline hemihydrate of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 13.4±0.2, 15.1±0.2, 20.9±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.

5. The crystalline hemihydrate of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 13.4±0.2, 15.1±0.2, 15.5±0.2, 17.0±0.2, 20.9±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.

6. The crystalline hemihydrate of claim 1 , wherein the crystalline hemihydrate is Freebase Hydrate Form C of (3 S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

7. The crystalline hemihydrate of claim 1 , having an X-ray powder diffraction pattern substantially as shown in FIG. 3C .

8. The crystalline hemihydrate of claim 1 , having a thermogravimetric analysis profile substantially as shown in FIG. 4E .

9. The crystalline hemihydrate of claim 1 , having a differential scanning calorimetry profile substantially as shown in FIG. 5C .

10. The crystalline hemihydrate of claim 1 , having a differential scanning calorimetry profile comprising an endotherm between about 120° C. and about 170° C. when heated at a rate of 10° C./minute.

11. The crystalline hemihydrate of claim 1 , having a moisture sorption isotherm profile substantially as shown in FIG. 6B .

12. The crystalline hemihydrate of claim 1 , having an orthorhombic lattice type that has a P2 1 2 1 2 1 space group, a unit cell a value of about 12.7 Å, a unit cell b value of about 13.1 Å, and a unit cell c value of about 22.6 Å.

13. A composition comprising a solid state form, wherein the solid state form is Freebase Hydrate Form C of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

14. The composition of claim 13 , comprising at least about 75% by weight of the Freebase Hydrate Form C of (3 S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrroline-1-carboxamide.

15. The composition of claim 13 , comprising at least about 95% by weight of the Freebase Hydrate Form C of (3 S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

16. A pharmaceutical composition comprising Freebase Hydrate Form C of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and a pharmaceutically acceptable carrier.

17. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises the Freebase Hydrate Form C in an amount sufficient to deliver about 7.5 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

18. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises the Freebase Hydrate Form C in an amount sufficient to deliver about 15 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

19. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises the Freebase Hydrate Form C in an amount sufficient to deliver about 30 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

20. The pharmaceutical composition of claim 16 , wherein the pharmaceutical composition comprises the Freebase Hydrate Form C in an amount sufficient to deliver about 45 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

21. A composition comprising a solid state form, wherein the solid state form is the crystalline hemihydrate of claim 2 .

22. The composition of claim 21 , comprising at least about 75% by weight of the crystalline hemihydrate.

23. The composition of claim 21 , comprising at least about 95% by weight of the crystalline hemihydrate.

24. A pharmaceutical composition comprising the crystalline hemihydrate of claim 2 and a pharmaceutically acceptable carrier.

25. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the crystalline hemihydrate in an amount sufficient to deliver about 7.5 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

26. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the crystalline hemihydrate in an amount sufficient to deliver about 15 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

27. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the crystalline hemihydrate in an amount sufficient to deliver about 30 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

28. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the crystalline hemihydrate in an amount sufficient to deliver about 45 mg of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide.

29. A process for preparing the pharmaceutical composition according to claim 16 , the process comprising combining the Freebase Hydrate Form C of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and the pharmaceutically acceptable carrier.

30. A process for preparing the pharmaceutical composition of claim 24 , comprising combining the crystalline hemihydrate and the pharmaceutically acceptable carrier.

Assignees

• Abbvie Inc

Inventors

• Allian Ayman

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title