Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-α]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-9879019-B2
Application number	US-201715682457-A
Country	US
Kind code	B2
Filing date	Aug 21, 2017
Priority date	Oct 16, 2015
Publication date	Jan 30, 2018
Grant date	Jan 30, 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

We claim:

1. A crystalline anhydrate 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 anhydrate of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 4.0±0.2, 14.5±0.2, and 19.0±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.

3. The crystalline anhydrate of claim 2 , having an X-ray powder diffraction pattern characterized by an additional peak at 14.2±0.2.

4. The crystalline anhydrate of claim 3 , having an X-ray powder diffraction pattern characterized by an additional peak at 9.7±0.2.

5. The crystalline anhydrate of claim 4 , having an X-ray powder diffraction pattern characterized by an additional peak at 20.3±0.2.

6. The crystalline anhydrate of claim 1 , wherein the crystalline anhydrate is Freebase Anhydrate Form D 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.

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

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

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

10. The crystalline anhydrate of claim 1 , having a differential scanning calorimetry profile comprising an endotherm between about 180° C. and about 220° C. when heated at a rate of 10° C./minute.

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

12. The crystalline anhydrate of claim 1 , having an orthorhombic lattice type that has a P2 1 2 1 2 space group, a unit cell a value of about 43.8 Å, a unit cell b value of about 8.6 Å, and a unit cell c value of about 9.2 Å.

13. A composition comprising a solid state form, wherein the solid state form is Freebase Anhydrate Form D 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 Anhydrate Form D 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.

15. The composition of claim 13 , comprising at least about 95% by weight of the Freebase Anhydrate Form D 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.

16. A pharmaceutical composition comprising Freebase Anhydrate Form D 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 Anhydrate Form D 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 Anhydrate Form D 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 Anhydrate Form D 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 Anhydrate Form D 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 anhydrate of claim 2 .

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

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

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

25. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the crystalline anhydrate 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 anhydrate 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 anhydrate 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 anhydrate 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 of claim 16 , the process comprising combining the Freebase Anhydrate Form D 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 anhydrate and the pharmaceutically acceptable carrier.

Assignees

• Abbvie Inc

Inventors

• Nordstroem Lars Frederick
• Sheikh Ahmad Y

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P37/08

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

• A61P7/00

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

• A61P43/00

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

• A61P35/00

  Antineoplastic agents · CPC title