Crystalline forms and salt forms of a kinase inhibitor
The present invention relates to crystalline forms of the free base of the c-Met inhibitor, Compound 1. The invention also relates to crystalline forms of salts of Compound 1. The invention also relates to pharmaceutical compositions comprising the solid polymorphs of the free base and salts of Compound 1. The invention further relates to methods of treating a disease, disorder, or syndrome mediated at least in part by modulating in vivo activity of a protein kinase.
1 . A crystalline hemifumarate Form B of Compound 1 having the structure
2 . The crystalline hemifumarate Form B of Compound 1 according to claim 1 , characterized by an X-ray powder diffraction pattern comprising peaks at 16.95, 19.16, and 26.34 degrees 2θ (±0.20 degrees).
3 . The crystalline hemifumarate Form B of Compound 1 according to claim 2 , characterized by an X-ray powder diffraction pattern further comprising peaks at 9.08, 24.37, and 27.05 degrees 2θ (±0.20 degrees).
4 . The crystalline hemifumarate Form B of Compound 1 according to claim 1 , characterized by an endotherm with an onset temperature of about 226° C. in a differential scanning calorimetry thermogram.
5 . The crystalline hemifumarate salt Form B of Compound 1 according to claim 1 , characterized by negligible weight loss under a temperature of about 220° C. in a thermogravimetric analysis thermogram.
6 . The crystalline hemifumarate Form B of Compound 1 according to claim 1 , characterized by an increase in weight of about 0.2 wt %, as measured by dynamic vapor sorption, in an environment that is taken from 5% relative humidity to 95% relative humidity.
7 . A Compound 1 hemifumarate having the structure
wherein said Compound 1 hemifumarate is in crystalline Form B and said Form B is characterized by an X-ray powder diffraction pattern comprising peaks at 9.08, 16.95, 19.16, and 26.34 degrees 2θ (±0.20 degrees).
8 . A Compound 1 hemifumarate having the structure
wherein said Compound 1 hemifumarate is in crystalline Form B and said Form B is characterized by an X-ray powder diffraction pattern substantially as depicted in FIG. 29 .
9 . The Compound 1 hemifumarate in crystalline Form B according to claim 7 , characterized by an endotherm with an onset temperature of about 226° C. in a differential scanning calorimetry thermogram.
10 . The Compound 1 hemifumarate in crystalline Form B according to claim 7 , characterized by negligible weight loss under a temperature of about 220° C. in a thermogravimetric analysis thermogram.
11 . The Compound 1 hemifumarate in crystalline Form B according to claim 7 , characterized by an increase in weight of about 0.2 wt %, as measured by dynamic vapor sorption, in an environment that is taken from 5% relative humidity to 95% relative humidity.