Crystalline forms of 2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)-1H-pyrazolo[3,4-D]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile
Crystalline forms of Compound (I): are disclosed. Pharmaceutical compositions comprising the same, methods of treating disorders and conditions mediated by BTK activity using the same, and methods for making Compound (I) and crystalline forms thereof are also disclosed.
1. Crystalline Form A of Compound (I):
wherein C* is a stereochemical center,
wherein crystalline Form A is characterized by an X-ray powder diffractogram having a signal at at least three two-theta values chosen from 5.6±0.2, 12.7±0.2, 16.5±0.2, 17.0±0.2, 17.7±0.2, 18.7±0.2, 19.2±0.2, 20.7±0.2, 22.2±0.2, and 24.4±0.2.
2. Crystalline Form A of Compound (I):
wherein C* is a stereochemical center,
wherein crystalline Form A is characterized by an X-ray powder diffractogram having a signal at at least three two-theta values chosen from 5.6±0.2, 12.7±0.2, 16.5±0.2, 17.0±0.2, 17.7±0.2, 18.7±0.2, 19.2±0.2, 20.7±0.2, 22.2±0.2, and 24.4±0.2; and
wherein crystalline Form A is further characterized by at least one characteristic chosen from:
a DSC thermogram having a peak endotherm (melting temperature) at about 146° C. to about 147° C.;
a DSC thermogram showing onset of melting at about 140.6° C. to about 141.2° C.;
a mass loss of less than 1.0 wt. % between 25° C. and 200° C. by thermogravimetric analysis; and
a water content of less than 1% upon storage at 95% relative humidity (RH).
3. Crystalline Form A of Compound (I):
wherein C* is a stereochemical center,
wherein crystalline Form A is characterized by an X-ray powder diffractogram having a signal at at least three two-theta values chosen from 5.6±0.2, 12.7±0.2, 16.5±0.2, 17.0±0.2, 17.7±0.2, 18.7±0.2, 19.2±0.2, 20.7±0.2, 22.2±0.2, and 24.4±0.2; and
wherein at least 95% of Compound (I) is the (E) isomer.
4. Crystalline Form B of Compound (I):
wherein C* is a stereochemical center,
wherein crystalline Form B is characterized by an X-ray powder diffractogram having a signal at at least three two-theta values chosen from 10.8±0.2, 15.3±0.2, 16.3±0.2, 17.9±0.2, 18.4±0.2, 18.7±0.2, 22.0±0.2, and 22.9±0.2.
5. Crystalline Form B according to claim 4 , wherein at least >99% of Compound (I) is the (E)-isomer.
6. Crystalline Form B according to claim 4 , wherein 95% to 99% of Compound (I) is the (E)-isomer.
7. Crystalline Form B of Compound (I):
wherein C* is a stereochemical center,
wherein crystalline Form B is characterized by an X-ray powder diffractogram having a signal at at least three two-theta values chosen from 10.8±0.2, 15.3±0.2, 16.3±0.2, 17.9±0.2, 18.4±0.2, 18.7±0.2, 22.0±0.2, and 22.9±0.2;
wherein at least >99% of Compound (I) is the (E)-isomer, and
wherein crystalline form B is further characterized by at least one characteristic chosen from:
a DSC thermogram having a peak endotherm (melting temperature) at about 144° C. to about 146° C.;
a DSC thermogram showing onset of melting at about 139.3° C.; and
a water content of less than 1.3% upon storage at 95% relative humidity (RH).
8. Crystalline Form B of Compound (I):
wherein C* is a stereochemical center,
wherein crystalline Form B is characterized by an X-ray powder diffractogram having a signal at at least three two-theta values chosen from 10.8±0.2, 15.3±0.2, 16.3±0.2, 17.9±0.2, 18.4±0.2, 18.7±0.2, 22.0±0.2, and 22.9±0.2;
wherein 95% to 99% of Compound (I) is the (E)-isomer, and
wherein crystalline form B is further characterized by at least one characteristic chosen from:
a DSC thermogram having a peak endotherm (melting temperature) at about 141° C. to about 142° C.;
a DSC thermogram showing onset of melting at about 131.8° C. to about 132.4° C.; and
a water content of less than 1.3% upon storage at 95% relative humidity (RH).
9. Crystalline Form C of Compound (I):
wherein C* is a stereochemical center,
wherein crystalline Form C is characterized by an X-ray powder diffractogram having a signal at at least three two-theta values chosen from 9.8±0.2, 10.2±0.2, 15.6±0.2, 16.6±0.2, 18.6±0.2, 18.9±0.2, 19.6±0.2, and 21.6±0.2.
10. Crystalline Form C of Compound (I):
wherein C* is a stereochemical center,
wherein crystalline Form C is characterized by an X-ray powder diffractogram having a signal at at least three two-theta values chosen from 9.8±0.2, 10.2±0.2, 15.6±0.2, 16.6±0.2, 18.6±0.2, 18.9±0.2, 19.6±0.2, and 21.6±0.2, and
wherein crystalline form C is further characterized by at least one characteristic chosen from:
a DSC thermogram having a peak endotherm (melting temperature) at about 118.5° C. to about 119° C., wherein the DSC scanning rate is 15° C./min;
a DSC thermogram showing onset of melting at about 115.6° C. to about 116° C., wherein the DSC scanning rate is 15° C./min;
a DSC thermogram having a peak endotherm (melting temperature) at about 120.5° C. to about 121° C., wherein the DSC scanning rate is 10° C./min;
a DSC thermogram showing onset of melting at about 118° C. to about 118.5° C., wherein the DSC scanning rate is 10° C./min;
a P-1 space group; and
the following unit cell dimensions at 200(2) K:
a = 10.6741 Å
α = 93.654°
b = 12.7684 Å
β = 104.400°
c = 14.5287 Å
γ = 105.476°.
11. Crystalline Form C according to claim 9 , wherein at least 95% of Compound (I) is the (E) isomer.