Crystalline form of (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide, preparation, and uses thereof
The present invention relates to a crystalline form of (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetra-hydropyrazolo[1,5-a]pyrimidine-3-carboxamide for inhibiting Btk, methods of preparation thereof and pharmaceutical compositions, and use of the crystalline form above in the treatment of a disease, or in the manufacturing of a medicament for the treatment of a disease.
1. Crystalline Form A of Compound 1,
made by crystallizing the crystalline Form A of Compound 1 from an amorphous form of Compound 1, wherein the crystalline Form A is characterized by an X-ray powder diffraction pattern comprising diffraction peaks having 2θ angle values at 14.8±0.2°, 16.4±0.2° and 21.4±0.2°.
2. The crystalline Form A of claim 1 , wherein the crystalline Form A has an enantiomeric excess value of at least 45%.
3. The crystalline Form A of claim 1 , wherein the crystalline Form A has a purity of at least 99.5%.
4. The crystalline Form A of claim 1 , wherein the crystalline Form A does not change its crystal form after being stored at about 80° C. for 2 days.
5. The crystalline Form A of claim 1 , wherein the crystalline Form A does not change its crystal form after being stored at about 25° C. under 60% relative humidity for up to 24 months.
6. The crystalline Form A of claim 1 , wherein the crystalline Form A does not change its crystal form after being stored at about 40° C. under 75% relative humidity for up to 6 months.
7. A pharmaceutical composition comprising the crystalline Form A of claim 1 and a pharmaceutically acceptable excipient.
8. A composition comprising the crystalline Form A of claim 1 and an amorphous form of Compound 1.
9. The composition of claim 8 , wherein the amorphous form has:
(i) a mid-point temperature of a glass transition temperature of about 79.7° C.; and/or
(ii) an enantiomeric excess value of at least 97%.
10. The Crystalline Form A of claim 1 , wherein the crystalline Form A is further characterized by an X-ray powder diffraction peak selected from 12.2±0.2°, 12.9±0.2°, and 15.6±0.2°.
11. Crystalline Form A of Compound 1,
wherein:
(i) the crystalline Form A is characterized by an X-ray powder diffraction pattern comprising diffraction peaks having 2θ angle values at 14.8±0.2°, 16.4±0.2° and 21.4±0.2°; and
(ii) the crystalline Form A
(a) does not change its crystal form after being stored at about 80° C. for 2 days;
(b) does not change its crystal form after being stored at about 25° C. under 60% relative humidity for up to 24 months; or
(c) does not change its crystal form after being stored at about 40° C. under 75% relative humidity for up to 6 months.
12. The crystalline Form A of claim 11 , wherein the crystalline Form A has a melting point onset temperature of 139±2° C.
13. The crystalline Form A of claim 11 , wherein the crystalline Form A has an enantiomeric excess value of at least 45%.
14. The crystalline Form A of claim 11 , wherein:
the crystalline Form A does not change its crystal form after being stored at about 80° C. for 2 days;
the crystalline Form A does not change its crystal form after being stored at about 25° C. under 60% relative humidity for up to 24 months; and
the crystalline Form A does not change its crystal form after being stored at about 40° C. under 75% relative humidity for up to 6 months.
15. The crystalline Form A of claim 11 , wherein the crystalline Form A has a purity of at least 99.5%.
16. A pharmaceutical composition comprising the crystalline Form A of claim 12 and a pharmaceutically acceptable excipient.
17. A composition comprising the crystalline Form A of claim 11 and an amorphous form of Compound 1.
18. The composition of claim 17 , wherein the amorphous form has:
(i) a mid-point temperature of a glass transition temperature of about 79.7° C.; and/or
(ii) an enantiomeric excess value of at least 97%.
19. The Crystalline Form A of claim 11 , wherein the crystalline Form A is further characterized by an X-ray powder diffraction peak selected from 12.2±0.2°, 12.9±0.2°, and 15.6±0.2°.
20. A composition comprising:
Crystalline Form A form of Compound 1,
wherein the crystalline form exhibits an X-ray powder diffraction pattern comprising diffraction peaks having 2θ angle values at 14.8±0.2°, 16.4±0.2° and 21.4±0.2°; and
an amorphous form of Compound 1.
21. The composition of claim 20 , wherein the crystalline Form A has a melting point onset temperature of 139±2° C.
22. The composition of claim 20 , wherein the crystalline Form A has an enantiomeric excess value of at least 45%.
23. The composition of claim 20 , wherein the crystalline Form A has a purity of at least 99.5%.
24. The composition of claim 20 , wherein the crystalline Form A does not change its crystal form after being stored at about 80° C. for 2 days.
25. The composition of claim 20 , wherein the crystalline Form A does not change its crystal form after being stored at about 25° C. under 60% relative humidity for up to 24 months.
26. The composition of claim 20 , wherein the crystalline Form A does not change its crystal form after being stored at about 40° C. under 75% relative humidity for up to 6 months.
27. The composition of claim 20 , wherein the amorphous form has a mid-point temperature of a glass transition temperature of about 79.7° C.
28. A pharmaceutical composition comprising the composition of claim 20 and a pharmaceutically acceptable excipient.
29. The composition of claim 20 , wherein the crystalline Form A is further characterized by an X-ray powder diffraction peak selected from 12.2±0.2°, 12.9±0.2°, and 15.6±0.2°.