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. A solid form 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 (Compound 1) comprising amorphous freebase or Freebase Hydrate Form C.
2. The solid form of claim 1 , wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises between about 0.8% and about 3.7% by weight water.
3. The solid form of claim 1 , wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises about 3.7% by weight water.
4. The solid form of claim 1 , wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises about 0.8% by weight water.
5. The solid form of claim 1 , wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises less than about 4% by weight water.
6. The solid form of claim 1 , wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises less than about 7% by weight water.
7. The solid form of claim 1 , wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises less than about 10% by weight water.
8. The solid form of claim 1 , wherein the solid form is the amorphous freebase, and wherein the amorphous freebase comprises less than 12% by weight water.
9. The solid form of claim 1 , wherein the amorphous freebase has glass transition temperature onset at about 119° C.
10. The solid form of claim 1 , wherein the amorphous freebase has glass transition temperature midpoint at about 122° C.
11. The solid form of claim 1 , wherein the solid form is the amorphous freebase, and wherein the amorphous freebase reversibly sorbs up to 13% water at 90% relative humidity at 25° C.
12. A process for preparing a pharmaceutical tablet, comprising contacting an amorphous freebase solid form 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 (Compound 1) with a pharmaceutically acceptable carrier, wherein the amorphous freebase comprises less than about 13% by weight water.
13. The process of claim 12 , wherein the amorphous freebase comprises less than about 10% by weight water.
14. The process of claim 13 , wherein the amorphous freebase comprises less than about 7% by weight water.
15. The process of claim 14 , wherein the amorphous freebase comprises less than about 4% by weight water.
16. The process of claim 15 , wherein the amorphous freebase comprises about 3.7% by weight water.
17. The process of claim 15 , wherein the amorphous freebase comprises about 0.8% by weight water.
18. The process of claim 15 , wherein the amorphous freebase comprises between about 0.8% and about 3.7% by weight water.
19. The process of claim 12 , wherein the amorphous freebase has a glass transition temperature midpoint at about 119° C.
20. The process of claim 12 , wherein the amorphous freebase has a glass transition temperature midpoint at about 122° C.
21. The process of claim 12 , wherein the amorphous freebase reversibly sorbs up to 13% water at 90% relative humidity at 25° C.
22. The solid form of claim 1 , wherein the amorphous freebase is characterized by having an X-ray powder diffraction pattern substantially as shown in FIG. 2 A .
23. The solid form of claim 1 , wherein the amorphous freebase is characterized by having an X-ray powder diffraction pattern substantially as shown in FIG. 2 B .
24. The solid form of claim 2 , wherein the amorphous freebase is characterized by having an X-ray powder diffraction pattern substantially as shown in FIG. 2 A .
25. The solid form of claim 2 , wherein the amorphous freebase is characterized by having an X-ray powder diffraction pattern substantially as shown in FIG. 2 B .
26. A pharmaceutical tablet comprising the solid form of claim 1 and a pharmaceutically acceptable carrier.
27. A pharmaceutical tablet comprising the solid form of claim 2 and a pharmaceutically acceptable carrier.
28. A pharmaceutical tablet comprising the solid form of claim 22 and a pharmaceutically acceptable carrier.
29. A pharmaceutical tablet comprising the solid form of claim 23 and a pharmaceutically acceptable carrier.
30. A pharmaceutical tablet comprising the solid form of claim 24 and a pharmaceutically acceptable carrier.
31. A pharmaceutical tablet comprising the solid form of claim 25 and a pharmaceutically acceptable carrier.