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 - 116 . (canceled)
117 . A safe and effective method of treating a human patient suffering from an inflammatory disease, comprising once daily oral administration to the patient of 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 (Compound 1), wherein the method safely achieves a clinically significant reduction in inflammation in the patient.
118 . The method of claim 117 , wherein the inflammatory disease is selected from the group consisting of inflammatory bowel disease, rheumatoid arthritis, juvenile idiopathic arthritis, a spondyloarthropathy, a skin condition, and vasculitis.
119 . The method of claim 117 , wherein the inflammatory disease has symptoms comprising skin inflammation, bowel inflammation, joint inflammation, or vascular inflammation.
120 . The method of claim 117 , wherein the inflammatory disease has symptoms comprising skin inflammation.
121 . The method of claim 120 , wherein the inflammatory disease is selected from the group consisting of atopic dermatitis, vitiligo, hidradenitis suppurativa, and alopecia areata.
122 . The method of claim 117 , wherein the inflammatory disease has symptoms comprising bowel inflammation.
123 . The method of claim 122 , wherein the inflammatory disease is selected from the group consisting of ulcerative colitis and Crohn's disease.
124 . The method of claim 117 , wherein the inflammatory disease has symptoms comprising joint inflammation.
125 . The method of claim 124 , wherein the inflammatory disease is selected from the group consisting of rheumatoid arthritis, juvenile idiopathic arthritis, a spondyloarthropathy, and systemic lupus erythematosus.
126 . The method of claim 117 , wherein the inflammatory disease has symptoms comprising vascular inflammation.
127 . The method of claim 126 , wherein the inflammatory disease is vasculitis.
128 . The method of claim 117 , wherein the inflammatory disease is selected from the group consisting of rheumatoid arthritis, juvenile idiopathic arthritis, a spondyloarthopathy, vasculitis, systemic lupus erythematosus, atopic dermatitis, vitiligo, hidradenitis suppurativa, alopecia areata, ulcerative colitis and Crohn's disease.
129 . The method of claim 117 , wherein the method results in a C-reactive protein (CRP) plasma concentration in the patient of less than the upper limit of normal (>5 mg/L).
130 . The method of claim 117 , wherein the patient has had an inadequate response or intolerance to one or more systemic disease-modifying antirheumatic drugs (DMARDS).
131 . The method of claim 130 , wherein the DMARD is an anti-TNF biologic.
132 . The method of claim 117 , wherein the 15 mg of Compound 1 is administered to the patient as 15.4 mg of crystalline hemihydrate Freebase Hydrate Form C.
133 . A safe and effective method of treating a human patient suffering from an inflammatory disease, comprising once daily oral administration to the patient of 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 (Compound 1), wherein the method safely achieves a clinically significant reduction in inflammation in the patient.
134 . The method of claim 133 , wherein the inflammatory disease is selected from the group consisting of inflammatory bowel disease, rheumatoid arthritis, juvenile idiopathic arthritis, a spondyloarthropathy, a skin condition, and vasculitis.
135 . The method of claim 133 , wherein the inflammatory disease has symptoms comprising skin inflammation, bowel inflammation, joint inflammation, or vascular inflammation.
136 . The method of claim 133 , wherein the inflammatory disease has symptoms comprising skin inflammation.
137 . The method of claim 136 , wherein the inflammatory disease is selected from the group consisting of atopic dermatitis, vitiligo, hidradenitis suppurativa, and alopecia areata.
138 . The method of claim 133 , wherein the inflammatory disease has symptoms comprising bowel inflammation.
139 . The method of claim 138 , wherein the inflammatory disease is selected from the group consisting of ulcerative colitis and Crohn's disease.
140 . The method of claim 133 , wherein the inflammatory disease has symptoms comprising joint inflammation.
141 . The method of claim 140 , wherein the inflammatory disease is selected from the group consisting of rheumatoid arthritis, juvenile idiopathic arthritis, a spondyloarthropathy, and systemic lupus erythematosus.
142 . The method of claim 133 , wherein the inflammatory disease is selected from the group consisting of rheumatoid arthritis, juvenile idiopathic arthritis, a spondyloarthopathy, vasculitis, systemic lupus erythematosus, atopic dermatitis, vitiligo, hidradenitis suppurativa, alopecia areata, ulcerative colitis and Crohn's disease.
143 . The method of claim 133 , wherein the method results in a C-reactive protein (CRP) plasma concentration in the patient of less than the upper limit of normal (>5 mg/L).
144 . The method of claim 133 , wherein the patient has had an inadequate response or intolerance to one or more systemic disease-modifying antirheumatic drugs (DMARDS).
145 . The method of claim 144 , wherein the DMARD is an anti-TNF biologic.
146 . The method of claim 133 , wherein the 30 mg of Compound 1 is administered to the patient as 30.7 mg of crystalline hemihydrate Freebase Hydrate Form C.