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 . An extended release tablet for oral administration, comprising:
(a) about 15 mg, about 30 mg or 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;
(b) microcrystalline cellulose;
(c) mannitol;
(d) hydroxypropyl methylcellulose;
(e) an organic acid selected from the group consisting of citric acid, succinic acid, fumaric acid, and tartaric acid;
(f) colloidal silica; and
(g) magnesium stearate.
118 . The extended release tablet of claim 117 , wherein the organic acid is citric acid.
119 . The extended release tablet of claim 117 , wherein the organic acid is succinic acid.
120 . The extended release tablet of claim 117 , wherein the organic acid is fumaric acid.
121 . The extended release tablet of claim 117 , wherein the organic acid is tartaric acid.
122 . An extended release tablet for oral administration, comprising:
(a) about 15 mg, about 30 mg or 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;
(b) microcrystalline cellulose;
(c) about 21 w/w % mannitol;
(d) about 20 w/w % hydroxypropyl methylcellulose;
(e) about 20 w/w % of an organic acid selected from the group consisting of citric acid, succinic acid, fumaric acid, and tartaric acid;
(f) about 0.5 w/w % colloidal silica; and
(g) about 1.5 w/w % magnesium stearate.
123 . The extended release tablet of claim 122 , wherein the organic acid is citric acid.
124 . The extended release tablet of claim 122 , wherein the organic acid is succinic acid.
125 . The extended release tablet of claim 122 , wherein the organic acid is fumaric acid.
126 . The extended release tablet of claim 122 , wherein the organic acid is tartaric acid.
127 . An extended release tablet for oral administration, comprising:
(a) about 15 mg or 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;
(b) about 30.6 w/w % to about 33.8 w/w % microcrystalline cellulose;
(c) about 21 w/w % mannitol;
(d) about 20 w/w % hydroxypropyl methylcellulose;
(e) about 20 w/w % of an organic acid selected from the group consisting of citric acid, succinic acid, fumaric acid, and tartaric acid;
(f) about 0.5 w/w % colloidal silica; and
(g) about 1.5 w/w % magnesium stearate.
128 . The extended release tablet of claim 127 , comprising:
(a) about 15 mg (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;
(b) about 33.8 w/w % microcrystalline cellulose;
(c) about 21 w/w % mannitol;
(d) about 20 w/w % hydroxypropyl methylcellulose;
(e) about 20 w/w % of an organic acid selected from the group consisting of citric acid, succinic acid, fumaric acid, and tartaric acid;
(f) about 0.5 w/w % colloidal silica; and
(g) about 1.5 w/w % magnesium stearate.
129 . The extended release tablet of claim 127 , comprising:
(a) about 30 mg (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;
(b) about 30.6 w/w % microcrystalline cellulose;
(c) about 21 w/w % mannitol;
(d) about 20 w/w % hydroxypropyl methylcellulose;
(e) about 20 w/w % of an organic acid selected from the group consisting of citric acid, succinic acid, fumaric acid, and tartaric acid;
(f) about 0.5 w/w % colloidal silica; and
(g) about 1.5 w/w % magnesium stearate.
130 . The extended release tablet of claim 127 , wherein the organic acid is citric acid.
131 . The extended release tablet of claim 127 , wherein the organic acid is succinic acid.
132 . The extended release tablet of claim 127 , wherein the organic acid is fumaric acid.
133 . The extended release tablet of claim 127 , wherein the organic acid is tartaric acid.
134 . The extended release tablet of claim 128 , wherein the organic acid is citric acid.
135 . The extended release tablet of claim 128 , wherein the organic acid is succinic acid.
136 . The extended release tablet of claim 128 , wherein the organic acid is fumaric acid.
137 . The extended release tablet of claim 128 , wherein the organic acid is tartaric acid.
138 . The extended release tablet of claim 129 , wherein the organic acid is citric acid.
139 . The extended release tablet of claim 129 , wherein the organic acid is succinic acid.
140 . The extended release tablet of claim 129 , wherein the organic acid is fumaric acid.
141 . The extended release tablet of claim 129 , wherein the organic acid is tartaric acid.