Claims for Patent: 10,981,924

Summary for Patent: 10,981,924

Title:	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
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):	Jayanth; Jayanthy (Buffalo, NY), Klunder; Ben (Ludwigshafen, DE), Mohamed; Mohamed-Eslam (Gurnee, IL), Othman; Ahmed A. (Waukegan, IL), Marroum; Patrick J. (Springfield, VA), Mayer; Peter T. (Libertyville, IL)
Assignee:	AbbVie Inc. (North Chicago, IL)
Application Number:	16/983,701
Patent Claims:	1. An oral extended-release tablet comprising (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") in an amount sufficient to deliver 15 mg of Compound 1 free base equivalent, wherein the tablet, when added to a test medium comprising 900 mL of 50 mM sodium phosphate buffer, at a pH of 6.8.+-.0.05, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at 75 rpm.+-.4%, releases: (i) not more than about 60% of Compound 1 after passage of about 4 hours; (ii) from about 50% to about 80% of Compound 1 after passage of about 8 hours; (iii) from about 55% to about 90% of Compound 1 after passage of about 10 hours; and (iv) from about 70% to about 100% of Compound 1 after passage of about 20 hours. 2. The tablet of claim 1, wherein Compound 1 is released at a steady rate. 3. The tablet of claim 1, wherein the tablet provides for the release of Compound 1 at a rate substantially independent of the pH of the test medium. 4. An oral extended-release tablet comprising (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") in an amount sufficient to deliver 30 mg of Compound 1 free base equivalent, wherein the tablet, when added to a test medium comprising 900 mL of 50 mM sodium phosphate buffer, at a pH of 6.8.+-.0.05, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at 75 rpm.+-.4%, releases: (i) not more than about 60% of Compound 1 after passage of about 4 hours; (ii) from about 50% to about 80% of Compound 1 after passage of about 8 hours; (iii) from about 55% to about 90% of Compound 1 after passage of about 10 hours; and (iv) from about 70% to about 100% of Compound 1 after passage of about 20 hours. 5. The tablet of claim 4, wherein Compound 1 is released at a steady rate. 6. The tablet of claim 4, wherein the tablet provides for the release of Compound 1 at a rate substantially independent of the pH of the test medium. 7. The tablet of claim 1, wherein when added to a test medium comprising 900 mL of 50 mM sodium phosphate buffer, at a pH of 6.8.+-.0.05, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at 75 rpm.+-.4%, releases between about 40% to about 60% after passage of about 4 hours. 8. The tablet of claim 1, wherein when added to a test medium comprising 900 mL of 50 mM sodium phosphate buffer, at a pH of 6.8.+-.0.05, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at 75 rpm.+-.4%, releases between about 60% to about 80% after passage of about 8 hours. 9. The tablet of claim 1, wherein when added to a test medium comprising 900 mL of 50 mM sodium phosphate buffer, at a pH of 6.8.+-.0.05, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at 75 rpm.+-.4%, releases between about 80% to about 100% after passage of about 20 hours. 10. The tablet of claim 4, wherein when added to a test medium comprising 900 mL of 50 mM sodium phosphate buffer, at a pH of 6.8.+-.0.05, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at 75 rpm.+-.4%, releases between about 40 to about 60% after passage of about 4 hours. 11. The tablet of claim 4, wherein when added to a test medium comprising 900 mL of 50 mM sodium phosphate buffer, at a pH of 6.8.+-.0.05, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at 75 rpm.+-.4%, releases between about 60 to about 80% after passage of about 8 hours. 12. The tablet of claim 4, wherein when added to a test medium comprising 900 mL of 50 mM sodium phosphate buffer, at a pH of 6.8.+-.0.05, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at 75 rpm.+-.4%, releases between about 80 to about 100% after passage of about 20 hours. 13. The tablet of claim 1, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases from about 10% to about 60% of Compound 1 after passage of about 1 to about 4 hours. 14. The tablet of claim 1, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases not less than about 70% of Compound 1 after passage of about 10 hours. 15. The tablet of claim 1, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases from about 60% to about 90% of Compound 1 after passage of about 4 to about 10 hours. 16. The tablet of claim 1, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases not less than about 90% of Compound 1 after passage of about 20 hours. 17. The tablet of claim 1, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases from about 90% to about 100% of Compound 1 after passage of about 10 hours to about 20 hours. 18. The tablet of claim 1, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases: (i) from about 10% to about 60% of Compound 1 after passage of about 1 to about 4 hours; (ii) not less than about 70% of Compound 1 after passage of about 10 hours; and (iii) not less than about 90% of Compound 1 after passage of about 20 hours. 19. The tablet of claim 1, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases: (i) from about 10% to about 60% of Compound 1 after passage of about 1 to about 4 hours; (ii) from about 60% to about 90% of Compound 1 after passage of about 4 to about 10 hours; and (iii) from about 90% to about 100% of Compound 1 after passage of about 10 hours to about 20 hours. 20. The tablet of claim 4, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases from about 10% to about 60% of Compound 1 after passage of about 1 to about 4 hours. 21. The tablet of claim 4, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases not less than about 70% of Compound 1 after passage of about 10 hours. 22. The tablet of claim 4, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases from about 60% to about 90% of Compound 1 after passage of about 4 to about 10 hours. 23. The tablet of claim 4, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases not less than about 90% of Compound 1 after passage of about 20 hours. 24. The tablet of claim 4, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases: (i) from about 10% to about 60% of Compound 1 after passage of about 1 to about 4 hours; (ii) not less than about 70% of Compound 1 after passage of about 10 hours; and (iii) not less than about 90% of Compound 1 after passage of about 20 hours. 25. The tablet of claim 4, wherein when added to a test medium comprising 500 mL of acidic medium at a pH of about 1.2, a temperature of 37.degree. C..+-.0.5.degree. C., in a standard USP rotating paddle apparatus, and when the paddles are rotated at .+-.4%, releases: (i) from about 10% to about 60% of Compound 1 after passage of about 1 to about 4 hours; (ii) from about 60% to about 90% of Compound 1 after passage of about 4 to about 10 hours; and (iii) from about 90% to about 100% of Compound 1 after passage of about 10 hours to about 20 hours.