Forms of a multicyclic compound
The present invention provides alternative forms of Compound I, processes to reproducibly make them and methods of treating patients using them.
1. A crystalline form of Compound I that is Form A 0 or Form B 0 , or a mixture thereof.
2. The crystalline form of claim 1 , wherein the crystalline form is Form A 0 .
3. The crystalline form of claim 1 , wherein the crystalline form is Form B 0 .
4. The crystalline form of claim 2 , characterized by an X-ray powder diffraction pattern comprising one or more of the following peaks: 4.32, 6.07, 8.55, 12.07 and 15.37±0.2 degrees 2-theta.
5. The crystalline form of claim 2 , having an X-ray powder diffraction pattern substantially as depicted in FIG. 1 .
6. The crystalline form of claim 3 , characterized by an X-ray powder diffraction pattern comprising one or more of the following peaks: 7.16, 7.89, 10.77, 16.54, and 21.20±0.2 degrees 2-theta.
7. The crystalline form of claim 3 , having an X-ray powder diffraction pattern substantially as depicted in FIG. 2 .
8. A crystalline form of Compound I that is Form HA 0 , Form HC 0 or Form HD 0 or a mixture thereof.
9. The crystalline form of claim 8 , wherein the crystalline form is Form HA 0 .
10. The crystalline form of claim 8 , wherein the crystalline form is Form HC 0 .
11. The crystalline form of claim 8 , wherein the crystalline form is Form HD 0 .
12. The crystalline form of claim 9 , characterized by an X-ray powder diffraction pattern comprising one or more of the following peaks: 7.59, 15.12, 16.06, 17.94 and 23.89±0.2 degrees 2-theta.
13. The crystalline form of claim 9 , having an X-ray powder diffraction pattern substantially as depicted in FIG. 3 .
14. The crystalline form of claim 10 , characterized by an X-ray powder diffraction pattern comprising one or more of the following peaks: 8.36, 8.71, 16.69, 17.39 and 24.59±0.2 degrees 2-theta.
15. The crystalline form of claim 10 , having an X-ray powder diffraction pattern substantially as depicted in FIG. 4 .
16. The crystalline form of claim 11 , characterized by an X-ray powder diffraction pattern comprising one or more of the following peaks: 7.60, 8.99 and 15.16±0.2 degrees 2-theta.
17. The crystalline form of claim 11 , having an X-ray powder diffraction pattern substantially as depicted in FIG. 5 .
18. A crystalline form of Compound I that is Form S2 0 , Form S3 0 , Form S4 0 , Form S5 0 , Form S6 0 , Form S7 0 , Form S9 0 , Form S10 0 or Form S12 0 or a mixture thereof.
19. A process for preparing a crystalline form of Compound I that is Form A 0 according to claim 2 , comprising the steps of:
a. Slurrying Compound I in a hydrocarbon(s) (such as heptane or toluene);
b. Cooling the resulting slurry;
c. Filtering the resulting slurry; and
d. Drying the filter-cake.
20. A process for preparing a crystalline form of Compound I that is Form A 0 according to claim 2 , comprising the steps of:
a. dissolving Compound I in a solvent;
b. filtering the resulting solution;
c. partially distilling the solvent while adding an anti-solvent to precipitate Compound I;
d. further distilling the resulting slurry while adding additional anti-solvent to reduce the volume of the solvent used in step (a);
e. heating the slurry to achieve complete conversion to Form A 0 ;
f. cooling;
g. collecting the product via filtration; and
h. drying.
21. A pharmaceutical composition comprising Form A 0 , Form B 0 , Form HA 0 , Form HC 0 , Form HD 0 , or a mixture thereof.
22. A pharmaceutical composition comprising Form A 0 , Form B 0 or a mixture thereof.