Crystalline forms of a PI3K inhibitor
The present invention is related to crystalline forms of (S)-7-(1-(9H-purin-6-ylamino) ethyl)-6-(3-fluorophenyl)-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one which is a PI3K inhibitor useful in the treatment of cancer and other diseases.
1. A crystalline form of the compound (S)-7-(1-(9H-purin-6-ylamino)ethyl)-6-(3-fluorophenyl)-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one which is hydrated.
2. The crystalline form of claim 1 which is a hemihydrate.
3. The crystalline form of claim 1 which is Form VI.
4. The crystalline form of claim 1 having an X-ray powder diffraction pattern comprising at least one peak, in terms of 2θ, at 10.7°±0.2°.
5. The crystalline form of claim 1 having an X-ray powder diffraction pattern comprising the following peaks, in terms of 2θ: 10.7°±0.2°; 14.6°±0.2°; 19.1°±0.2°; and 23.9°±0.2°.
6. The crystalline form of claim 1 having an X-ray powder diffraction pattern comprising 4 or more of the following peaks, in terms of 2θ: 10.7°±0.2°; 14.6°±0.2°; 16.0°±0.2°; 19.1°±0.2°; 22.4 ±0.2″; 23.9°±0.2°; 24.5 ±0.2°; 26.7°±0.2°; 29.1°±0.2°; 30.3°±0.2°; and 34.7°±0.2°.
7. The crystalline form of claim 1 having an X-ray powder diffraction pattern substantially as shown in FIG. 16 .
8. The crystalline form of claim 1 having a differential scanning calorimetry thermogram (DSC) substantially as shown in FIG. 17 (upper, Cycle 1).
9. The crystalline form of claim 1 having a thermogravimetric analysis (TGA) substantially as shown in FIG. 18 .
10. The crystalline form of claim 1 which is substantially isolated.
11. A composition comprising the crystalline form of claim 1 .
12. The composition of claim 11 wherein said composition comprises at least one pharmaceutically acceptable carrier.
13. A process for preparing the crystalline form of claim 1 comprising combining the compound (S)-7-(1-(9H-purin-6-ylamino)ethyl)-6-(3-fluorophenyl)-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one with water.
14. The process of claim 13 further comprising heating the mixture resulting from the combining of said compound and water.
15. A crystalline form of the compound (S)-7-(1-(9H-purin-6-ylamino)ethyl)-6-(3-fluorophenyl)-3-methyl-5H-thiazolo[3,2-a]pyrimidin-5-one which is Form X.
16. The crystalline form of claim 15 having an X-ray powder diffraction pattern comprising at least one peak, in terms of 2θ, at 6.8°±0.2°.
17. The crystalline form of claim 15 having an X-ray powder diffraction pattern comprising the following peaks, in terms of 2θ: 6.8°±0.2°; 13.5°±0.2°; 20.2°±0.2°; and 21.7°±0.2°.
18. The crystalline form of claim 15 having an X-ray powder diffraction pattern comprising 4 or more of the following peaks, in terms of 2θ: 6.8°±0.2°; 10.5°±0.2°; 13.5°±0.2°; 14.8°±0.2°; 17.0°±0.2°; 19.6°±0.2°; 20.2°±0.2°; 21.7°±0.2′; 25.0°±0.2′; 26.3°±0.2°; and 29.6°±0.2°.
19. The crystalline form of claim 15 having an X-ray powder diffraction pattern substantially as shown in FIG. 28 .
20. The crystalline form of claim 15 having a differential scanning calorimetry (DSC) thermogram characterized by an endotherm at 258±4° C.
21. The crystalline form of claim 15 having a differential scanning calorimetry thermogram (DSC) substantially as shown in FIG. 29 .
22. The crystalline form of claim 15 having a thermogravimetric analysis (TGA) substantially as shown in FIG. 30 .
23. The crystalline form of claim 15 which is substantially isolated.
24. A composition comprising the crystalline form of claim 15 .
25. The composition of claim 24 wherein said composition comprises at least one pharmaceutically acceptable carrier.
26. A process for preparing the crystalline form of claim 15 comprising combining crystalline Form I of the compound (S)-7-(1-(9H-purin-6-ylamino)ethyl)-6-(fluorophenyl)-3-methyl-5H-thiazolo [3,2-a]pyrimidin-5-one with acetone.
27. The process of claim 26 further comprising heating the mixture resulting from the combining of said crystalline Form I and acetone.