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
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. 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.