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 and solid state forms thereof

Patent metadata

Field	Value
Publication number	US-9879018-B2
Application number	US-201715682451-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. Amorphous freebase (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 amorphous freebase of claim 1 , having an X-ray powder diffraction pattern substantially as shown in FIG. 2A .

3. The amorphous freebase of claim 1 , having an X-ray powder diffraction pattern substantially as shown in FIG. 2B .

4. The amorphous freebase of claim 1 , having a thermogravimetric analysis profile substantially as shown in FIG. 4A .

5. The amorphous freebase of claim 1 , having a thermogravimetric analysis profile substantially as shown in FIG. 4B .

6. The amorphous freebase of claim 1 , having a differential scanning calorimetry profile substantially as shown in FIG. 5A .

7. The amorphous freebase of claim 1 , having a glass transition temperature onset at about 119° C.

8. The amorphous freebase of claim 1 , having a glass transition temperature midpoint at about 122° C.

9. The amorphous freebase of claim 1 , having a moisture sorption isotherm profile substantially as shown in FIG. 6A .

10. The amorphous freebase of claim 1 , comprising less than 13% by weight water.

11. A composition comprising a solid state form, wherein the solid state form is amorphous freebase 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.

12. The composition of claim 11 , comprising at least about 75% by weight of the amorphous freebase 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.

13. The composition of claim 11 , comprising at least about 95% by weight of the amorphous freebase 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. A pharmaceutical composition comprising amorphous freebase 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 and a pharmaceutically acceptable carrier.

15. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition comprises the amorphous freebase in an amount sufficient to deliver about 7.5 mg 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. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition comprises the amorphous freebase in an amount sufficient to deliver about 15 mg 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.

17. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition comprises the amorphous freebase in an amount sufficient to deliver about 30 mg 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.

18. The pharmaceutical composition of claim 14 , wherein the pharmaceutical composition comprises the amorphous freebase in an amount sufficient to deliver about 45 mg 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.

19. A pharmaceutical composition comprising the amorphous freebase of claim 2 and a pharmaceutically acceptable carrier.

20. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition comprises the amorphous freebase in an amount sufficient to deliver about 7.5 mg 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.

21. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition comprises the amorphous freebase in an amount sufficient to deliver about 15 mg 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.

22. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition comprises the amorphous freebase in an amount sufficient to deliver about 30 mg 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.

23. The pharmaceutical composition of claim 19 , wherein the pharmaceutical composition comprises the amorphous freebase in an amount sufficient to deliver about 45 mg 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.

24. A pharmaceutical composition comprising the amorphous freebase of claim 3 and a pharmaceutically acceptable carrier.

25. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the amorphous freebase in an amount sufficient to deliver about 7.5 mg 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.

26. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the amorphous freebase in an amount sufficient to deliver about 15 mg 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.

27. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the amorphous freebase in an amount sufficient to deliver about 30 mg 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.

28. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises the amorphous freebase in an amount sufficient to deliver about 45 mg 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.

29. A process for preparing the pharmaceutical composition of claim 14 , the process comprising combining the amorphous freebase 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 and the pharmaceutically acceptable carrier.

30. A process for preparing the pharmaceutical composition of claim 19 , comprising combining the amorphous freebase 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.

Assignees

• Abbvie Inc

Inventors

• Mulhern Mathew M
• Nordstroem Lars Fredrick
• Sheikh Ahmad Y

Classifications

• A61P7/00

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/02

  Immunomodulators · 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