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-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.
1. Crystalline (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 (Compound 1) selected from the group consisting of:
a. crystalline freebase Compound 1 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;
b. crystalline freebase Compound 1 having an X-ray powder diffraction pattern characterized by peaks at 3.1±0.2, 9.4±0.2 and 21.1±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation; and
c. crystalline freebase Compound 1 having an X-ray powder diffraction pattern characterized by peaks at 3.1±0.2, 9.3±0.2 and 20.8±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
2. A process for preparing a pharmaceutical composition comprising 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 (Compound 1), the process comprising contacting a crystalline freebase Compound 1 with a pharmaceutically acceptable carrier, wherein the crystalline freebase Compound 1 is selected from the group consisting of:
a. crystalline freebase Compound 1 having an X-ray powder diffraction pattern characterized by peaks at 3.1±0.2, 9.4±0.2 and 21.1±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation; and
b. crystalline freebase Compound 1 having an X-ray powder diffraction pattern characterized by peaks at 3.1±0.2, 9.3±0.2 and 20.8±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation;
wherein the crystalline freebase Compound 1 is converted into amorphous freebase of Compound 1.
3. The crystalline freebase Compound 1 of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 3.1±0.2, 9.4±0.2 and 21.1±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
4. The crystalline freebase Compound 1 of claim 3 , further characterized by at least one additional peak selected from the group consisting of 5.4±0.2, 12.1±0.2 and 19.1±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
5. The crystalline freebase Compound 1 of claim 3 , which is an isopropyl acetate/water solvate.
6. The crystalline freebase Compound 1 of claim 1 , having an X-ray powder diffraction pattern characterized by peaks at 3.1±0.2, 9.3±0.2 and 20.8±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
7. The crystalline freebase Compound 1 of claim 6 , further characterized by at least one additional peak selected from the group consisting of 12.0±0.2 and 25.0±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
8. The crystalline freebase Compound 1 of claim 6 , which is a hydrate.
9. The process of claim 2 , wherein the contacting comprises dispersing the crystalline freebase Compound 1 in the pharmaceutically acceptable carrier.
10. The process of claim 2 , wherein the pharmaceutically acceptable carrier is a hydrophilic polymer.
11. The process of claim 2 , wherein at least about 80% by weight of the crystalline freebase Compound 1 is converted into the amorphous freebase Compound 1.
12. The process of claim 2 , wherein at least about 98% by weight of the crystalline freebase Compound 1 is converted into the amorphous freebase Compound 1.
13. The process of claim 2 , wherein the crystalline freebase Compound 1 has an X-ray powder diffraction pattern characterized by peaks at 3.1±0.2, 9.4±0.2 and 21.1±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
14. The process of claim 13 , wherein the crystalline freebase Compound 1 is further characterized by at least one additional peak selected from the group consisting of 5.4±0.2, 19.1±0.2 and 12.1±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
15. The process of claim 13 , wherein the crystalline freebase Compound 1 is an isopropyl acetate/water solvate.
16. The process of claim 2 , wherein the crystalline freebase Compound 1 has an X-ray powder diffraction pattern characterized by peaks at 3.1±0.2, 9.3±0.2 and 20.8±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
17. The process of claim 16 , wherein the crystalline freebase Compound 1 is further characterized by at least one additional peak selected from the group consisting of 12.0±0.2 and 25.0±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
18. The process of claim 16 , wherein the crystalline freebase Compound 1 is a hydrate.
19. A process for preparing a pharmaceutical composition comprising 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 (Compound 1), the process comprising contacting a crystalline freebase Compound 1 with a pharmaceutically acceptable carrier, wherein the crystalline freebase Compound 1 is selected from the group consisting of:
a. crystalline freebase Compound 1 having an X-ray powder diffraction pattern characterized by peaks at 3.1±0.2, 9.4±0.2 and 21.1±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation; and
b. crystalline freebase Compound 1 having an X-ray powder diffraction pattern characterized by peaks at 3.1±0.2, 9.3±0.2 and 20.8±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
20. The process of claim 19 , wherein the crystalline freebase Compound 1 has an X-ray powder diffraction pattern characterized by peaks at 3.1±0.2, 9.4±0.2 and 21.1±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
21. The process of claim 20 , wherein the crystalline freebase Compound 1 is further characterized by at least one additional peak selected from the group consisting of 5.4±0.2, 12.1±0.2 and 19.1±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
22. The process of claim 20 , wherein the crystalline freebase Compound 1 has an X-ray powder diffraction pattern characterized by peaks at 3.1±0.2, 9.3±0.2 and 20.8±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.
23. The process of claim 22 , wherein the crystalline freebase Compound 1 is further characterized by at least one additional peak selected from the group consisting of 12.0±0.2 and 25.0±0.2 degrees two theta when measured at about 25° C. with monochromatic Kα1 radiation.