Solid state forms of (S)-N-(3-(2-(((R)-1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and salts thereof
The present disclosure relates to solid state forms of (S)—N-(3-(2-(((R)-1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and salts thereof. Such solid state forms are useful in preparation of pharmaceutical compositions and dosage forms for the treatment of disease.
1 . A solid form of(S)—N-(3-(2-(((R)-1-hydroxypropan-2-yl)amino)-6-morpholinopyridin-4-yl)-4-methylphenyl)-3-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide hydrochloride, depicted below as Compound 2,
wherein the solid form is crystalline.
2 . The solid form of claim 1 , wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 19.7°±0.3.
3 . The solid form of claim 2 , wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 11.1°±0.3 and 21.2°±0.3.
4 . The solid form of claim 2 , wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 15.8°±0.3 and 22.0°=0.3.
5 . The solid form of claim 2 , wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 13.9°±0.3, 18.5° 0.3, 21.7°±0.3, and 22.5°±0.3.
6 . The solid form of claim 2 , wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of 9.7°±0.3, 23.3°±0.3, and 23.8°±0.3.
7 . The solid form of claim 1 , wherein the solid form exhibits at least one X-ray powder diffraction reflection selected from 9.7°±0.3, 11.1°±0.3, 13.9°±0.3, 15.8°±0.3, 18.5°±0.3, 19.7°±0.3, 21.2°±0.3, 21.7°±0.3, 22.0°±0.3, 22.5°±0.3, 23.3°±0.3, and 23.8°=0.3.
8 . The solid form of claim 7 , wherein the solid form exhibits at least two X-ray powder diffraction reflections selected from 9.7°±0.3, 11.1°±0.3, 13.9°±0.3, 15.8°±0.3, 18.5°±0.3, 19.7°±0.3, 21.2°±0.3, 21.7°±0.3, 22.0°±0.3, 22.5°±0.3, 23.3°±0.3, and 23.8°±0.3.
9 . The solid form of claim 8 , wherein the solid form exhibits at least three X-ray powder diffraction reflections selected from 9.7°±0.3, 11.1°±0.3, 13.9°±0.3, 15.8°±0.3, 18.5°±0.3, 19.7°±0.3, 21.2°±0.3, 21.7°±0.3, 22.0°±0.3, 22.5°±0.3, 23.3°±0.3, and 23.8°=0.3.
10 . The solid form of claim 9 , wherein the solid form exhibits at least four X-ray powder diffraction reflections selected from 9.7°±0.3, 11.1°±0.3, 13.9°±0.3, 15.8°±0.3, 18.5°±0.3, 19.7°±0.3, 21.2°±0.3, 21.7°±0.3, 22.0°±0.3, 22.5°±0.3, 23.3°±0.3, and 23.8°±0.3.
11 . The solid form of claim 10 , wherein the solid form exhibits at least five X-ray powder diffraction reflections selected from 9.7°±0.3, 11.1°±0.3, 13.9°±0.3, 15.8°±0.3, 18.5°±0.3, 19.7°±0.3, 21.2°±0.3, 21.7°±0.3, 22.0°±0.3, 22.5°±0.3, 23.3°±0.3, and 23.8°±0.3.
12 . The solid form of claim 11 , wherein the solid form exhibits at least six X-ray powder diffraction reflections selected from 9.7°±0.3, 11.1°±0.3, 13.9°±0.3, 15.8°±0.3, 18.5°±0.3, 19.7°±0.3, 21.2°=0.3, 21.7°±0.3, 22.0°±0.3, 22.5°±0.3, 23.3°±0.3, and 23.8°±0.3.
13 . The solid form of claim 1 , wherein the solid form exhibits an X-ray powder diffraction reflection at a 2-theta value of the crystalline solid state form of Compound 2 exhibits at least one X-ray powder diffraction reflection selected from 20.3°±0.2, 23.4°±0.2, and 24.0°±0.2.
14 . The solid form of claim 1 , wherein the solid form exhibits the X-ray powder diffraction pattern as shown in FIG. 3 .
15 . The solid form of claim 1 , wherein the solid form exhibits a differential scanning calorimetry thermogram comprising an endothermic peak at 229.9° C.±5.0.
16 . The solid form of claim 1 , wherein the solid form exhibits the differential scanning calorimetry thermogram as shown in FIG. 4 .
17 . The solid form of claim 1 , wherein the solid form exhibits less than 1.0%±0.5 weight loss up to 160° C.±10.0 as determined by thermogravimetric analysis.
18 . The solid form of claim 1 , wherein the solid form exhibits the thermogravimetric analysis thermogram as shown in FIG. 4 .
19 . A pharmaceutical composition comprising the solid form of claim 1 and a pharmaceutically acceptable excipient.
20 . The pharmaceutical composition of claim 19 , further comprising a disintegrating agent.
21 . The pharmaceutical composition of claim 20 , wherein the disintegrating agent is croscarmellose sodium.
22 . A method of inhibiting receptor tyrosine kinase effector RAF comprising administering to the subject with a condition in need thereof, the solid form of claim 1 .
23 . The method of claim 22 , wherein the condition is cancer or neoplastic disease.