Processes for the preparation 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 solid state forms thereof
The present disclosure relates to processes for preparing (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, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis), kits, methods of synthesis, and products-by-process.
1. Crystalline 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 having an X-ray powder diffraction pattern characterized by peaks at 15.5±0.2, 17.0±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
2. The crystalline freebase of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 15.1 0.2, 15.5±0.2, 17.0±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
3. The crystalline freebase 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, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
4. The crystalline freebase of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 10.3±0.2, 13.4±0.2, 15.1±0.2, 15.5±0.2, 17.0±0.2, and 21.7 ±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
5. The crystalline freebase of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 10.3±0.2, 13.4±0.2, 15.1±0.2, 15.5±0.2, 17.0±0.2, 17.8±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
6. The crystalline freebase of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 7.7±0.2, 7.9±0.2, 10.3±0.2, 13.4±0.2, 15.1±0.2, 15.5±0.2, 17.0±0.2, 17.8±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
7. The crystalline freebase of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 12.4±0.2, 15.5±0.2, 17.0±0.2, 21.7±0.2, and 23.5±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
8. The crystalline freebase of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 12.4±0.2, 15.5±0.2, 17.0±0.2, 17.2±0.2, 20.9±0.2, 21.7 ±0.2, and 23.5±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
9. The crystalline freebase of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 12.4±0.2, 15.5±0.2, 17.0±0.2, 17.2±0.2, 19.3±0.2, 20.9±0.2, 21.7±0.2, 23.5±0.2, and 24.9±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
10. The crystalline freebase of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 12.4±0.2, 15.5±0.2, 17.0±0.2, 17.2±0.2, 18.1±0.2, 19.3±0.2, 20.9±0.2, 21.7±0.2, 22.2±0.2, 23.5±0.2, and 24.9±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
11. The crystalline freebase of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 12.4±0.2, 15.5±0.2, 17.0±0.2, 17.2±0.2, 18.1±0.2, 19.3±0.2, 20.9±0.2, 21.7±0.2, 22.2±0.2, 23.5±0.2, 24.9±0.2, and 29.2±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
12. The crystalline freebase of claim 1 , wherein the crystalline 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 is an anhydrate.
13. The crystalline freebase of claim 1 , wherein the crystalline 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 is a hydrate.
14. The crystalline freebase of claim 13 , wherein the crystalline 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 is a hemihydrate.
15. The crystalline freebase of claim 1 , wherein the crystalline 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 is a solvate.
16. A pharmaceutical composition comprising crystalline 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 having an X-ray powder diffraction pattern characterized by peaks at 15.5±0.2, 17.0±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation, and a pharmaceutically acceptable carrier.
17. The pharmaceutical composition of claim 16 , wherein the crystalline freebase has an X-ray powder diffraction pattern characterized by peaks at 15.1±0.2, 15.5±0.2, 17.0 ±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
18. The pharmaceutical composition of claim 16 , wherein the crystalline freebase has 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, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
19. The pharmaceutical composition of claim 16 , wherein the crystalline freebase has an X-ray powder diffraction pattern characterized by peaks at 10.3±0.2, 13.4±0.2, 15.1 ±0.2, 15.5±0.2, 17.0±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
20. The pharmaceutical composition of claim 16 , wherein the crystalline freebase has an X-ray powder diffraction pattern characterized by peaks at 10.3±0.2, 13.4±0.2, 15.1 ±0.2, 15.5±0.2, 17.0±0.2, 17.8±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
21. The pharmaceutical composition of claim 16 , wherein the crystalline freebase has an X-ray powder diffraction pattern characterized by peaks at 7.7±0.2, 7.9±0.2, 10.3 ±0.2, 13.4±0.2, 15.1±0.2, 15.5±0.2, 17.0±0.2, 17.8±0.2, and 21.7±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
22. The pharmaceutical composition of claim 16 , wherein the crystalline freebase has an X-ray powder diffraction pattern characterized by peaks at 12.4±0.2, 15.5±0.2, 17.0 ±0.2, 21.7±0.2, and 23.5±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
23. The pharmaceutical composition of claim 16 , wherein the crystalline freebase has an X-ray powder diffraction pattern characterized by peaks at 12.4±0.2, 15.5±0.2, 17.0 ±0.2, 17.2±0.2, 20.9±0.2, 21.7±0.2, and 23.5±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
24. The pharmaceutical composition of claim 16 , wherein the crystalline freebase has an X-ray powder diffraction pattern characterized by peaks at 12.4±0.2, 15.5±0.2, 17.0 ±0.2, 17.2±0.2, 19.3±0.2, 20.9±0.2, 21.7±0.2, 23.5±0.2, and 24.9±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
25. The pharmaceutical composition of claim 16 , wherein the crystalline freebase has an X-ray powder diffraction pattern characterized by peaks at 12.4±0.2, 15.5±0.2, 17.0 ±0.2, 17.2±0.2, 18.1±0.2, 19.3±0.2, 20.9±0.2, 21.7±0.2, 22.2±0.2, 23.5±0.2, and 24.9±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
26. The pharmaceutical composition of claim 16 , wherein the crystalline freebase has an X-ray powder diffraction pattern characterized by peaks at 12.4±0.2, 15.5±0.2, 17.0 ±0.2, 17.2±0.2, 18.1±0.2, 19.3±0.2, 20.9±0.2, 21.7±0.2, 22.2±0.2, 23.5±0.2, 24.9 ±0.2, and 29.2±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
27. The pharmaceutical composition of claim 16 , wherein the crystalline 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 is an anhydrate.
28. The pharmaceutical composition of claim 16 , wherein the crystalline 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 is a hydrate.
29. The pharmaceutical composition of claim 16 , wherein the crystalline 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 is a hemihydrate.
30. The pharmaceutical composition of claim 16 , wherein the crystalline 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 is a solvate.