Claims for Patent: 9,951,080

Summary for Patent: 9,951,080

Title:	Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-alpha]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2- ,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof
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.
Inventor(s):	Allian; Ayman (Gurnee, IL)
Assignee:	AbbVie Inc. (North Chicago, IL)
Application Number:	15/803,538
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,951,080
Patent Claims:	1. A crystalline hemihydrate 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. 2. The crystalline hemihydrate of claim 1, having an X-ray powder diffraction pattern characterized by peaks at 13.4.+-.0.2, 15.1.+-.0.2, and 21.7.+-.0.2 degrees two theta when measured at about 25.degree. C. with monochromatic K.alpha.1 radiation. 3. The crystalline hemihydrate of claim 1, having an X-ray powder diffraction pattern characterized by peaks at 13.4.+-.0.2, 15.1.+-.0.2, 17.0.+-.0.2, and 21.7.+-.0.2 degrees two theta when measured at about 25.degree. C. with monochromatic K.alpha.1 radiation. 4. The crystalline hemihydrate of claim 1, having an X-ray powder diffraction pattern characterized by peaks at 13.4.+-.0.2, 15.1.+-.0.2, 20.9.+-.0.2, and 21.7.+-.0.2 degrees two theta when measured at about 25.degree. C. with monochromatic K.alpha.1 radiation. 5. The crystalline hemihydrate 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, 20.9.+-.0.2, and 21.7.+-.0.2 degrees two theta when measured at about 25.degree. C. with monochromatic K.alpha.1 radiation. 6. The crystalline hemihydrate of claim 1, wherein the crystalline hemihydrate is Freebase Hydrate Form C of (3 S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-tr- ifluoroethyl)pyrrolidine-1-carboxamide. 7. The crystalline hemihydrate of claim 1, having an X-ray powder diffraction pattern substantially as shown in FIG. 3C. 8. The crystalline hemihydrate of claim 1, having a thermogravimetric analysis profile substantially as shown in FIG. 4E. 9. The crystalline hemihydrate of claim 1, having a differential scanning calorimetry profile substantially as shown in FIG. 5C. 10. The crystalline hemihydrate of claim 1, having a differential scanning calorimetry profile comprising an endotherm between about 120.degree. C. and about 170.degree. C. when heated at a rate of 10.degree. C./minute. 11. The crystalline hemihydrate of claim 1, having a moisture sorption isotherm profile substantially as shown in FIG. 6B. 12. The crystalline hemihydrate of claim 1, having an orthorhombic lattice type that has a P2.sub.12.sub.12.sub.1 space group, a unit cell a value of about 12.7 .ANG., a unit cell b value of about 13.1 .ANG., and a unit cell c value of about 22.6 .ANG.. 13. A composition comprising a solid state form, wherein the solid state form is Freebase Hydrate Form C 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. The composition of claim 13, comprising at least about 75% by weight of the Freebase Hydrate Form C of (3 S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-tr- ifluoroethyl)pyrroline-1-carboxamide. 15. The composition of claim 13, comprising at least about 95% by weight of the Freebase Hydrate Form C of (3 S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-tr- ifluoroethyl)pyrrolidine-1-carboxamide. 16. A pharmaceutical composition comprising Freebase Hydrate Form C 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 a pharmaceutically acceptable carrier. 17. The pharmaceutical composition of claim 16, wherein the pharmaceutical composition comprises the Freebase Hydrate Form C in an amount sufficient to deliver about 7.5 mg 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. 18. The pharmaceutical composition of claim 16, wherein the pharmaceutical composition comprises the Freebase Hydrate Form C in an amount sufficient to deliver about 15 mg 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. 19. The pharmaceutical composition of claim 16, wherein the pharmaceutical composition comprises the Freebase Hydrate Form C in an amount sufficient to deliver about 30 mg 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. 20. The pharmaceutical composition of claim 16, wherein the pharmaceutical composition comprises the Freebase Hydrate Form C in an amount sufficient to deliver about 45 mg 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. 21. A composition comprising a solid state form, wherein the solid state form is the crystalline hemihydrate of claim 2. 22. The composition of claim 21, comprising at least about 75% by weight of the crystalline hemihydrate. 23. The composition of claim 21, comprising at least about 95% by weight of the crystalline hemihydrate. 24. A pharmaceutical composition comprising the crystalline hemihydrate of claim 2 and a pharmaceutically acceptable carrier. 25. The pharmaceutical composition of claim 24, wherein the pharmaceutical composition comprises the crystalline hemihydrate in an amount sufficient to deliver about 7.5 mg 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. 26. The pharmaceutical composition of claim 24, wherein the pharmaceutical composition comprises the crystalline hemihydrate in an amount sufficient to deliver about 15 mg 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. 27. The pharmaceutical composition of claim 24, wherein the pharmaceutical composition comprises the crystalline hemihydrate in an amount sufficient to deliver about 30 mg 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. 28. The pharmaceutical composition of claim 24, wherein the pharmaceutical composition comprises the crystalline hemihydrate in an amount sufficient to deliver about 45 mg 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. 29. A process for preparing the pharmaceutical composition according to claim 16, the process comprising combining the Freebase Hydrate Form C 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. 30. A process for preparing the pharmaceutical composition of claim 24, comprising combining the crystalline hemihydrate and the pharmaceutically acceptable carrier.