Heterocyclic compounds, preparation methods and uses thereof
Provided herein are compounds, crystalline forms, and pharmaceutical compositions of Compound 1 and/or Compound 2. Also provided are methods of treating a disease or disorder such as a cancer or infectious disease that comprises administering to a subject in need thereof one or more of the compounds or compositions of the present disclosure.
1. A crystalline form of Compound 2:
wherein the crystalline form is Form B, characterized by an X-ray powder diffraction (XRPD) pattern (i) having all of the following peaks 6.2, 12.6, 14.8, 19.0, and 19.8 degrees 2 theta, ±0.2°; and (ii) having at least one of the following peaks: 14.5, 17.8, 21.4, 26.3, 31.9 and 38.6 degrees 2 theta, ±0.2°.
2. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern (i) having all of the following peaks 6.2, 12.6, 14.8, 19.0, and 19.8 degrees 2 theta, ±0.2°; and (ii) having all of the following peaks: 14.5, 17.8, 21.4, 26.3, 31.9 and 38.6 degrees 2 theta, ±0.2°.
3. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern (i) having all of the following peaks: 6.2, 12.6, 14.8, 19.0, and 19.8 degrees 2 theta, ±0.2°; (i) having two or more of the following peaks: 14.5, 15.6, 20.2, and 38.6 degrees 2 theta, ±0.2°; and (iii) not having one or both peaks at 7.3 and 14.2 degrees 2 theta, ±0.2°.
4. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern (i) having all of the following peaks: 6.2, 12.6, 13.6, 14.5, 14.8, 15.6, 17.8, 19.0, 19.8, 20.2, 21.4, 26.3, 31.9 and 38.6 degrees 2 theta, ±0.2°; and (ii) not having one or both peaks at 7.3 and 14.2 degrees 2 theta, ±0.2°.
5. The crystalline form of claim 1 , further characterized by a Differential Scanning calorimetry (DSC) pattern having an endothermic peak with an onset temperature of about 289.0° C. and/or peak temperature at about 290.1° C.
6. A method of preparing of Compound 2 in crystalline Form B, the method comprising:
1) dissolving Compound 2 in a first solvent to form a solution; and
2) adding an anti-solvent to the solution to precipitate Compound 2 in crystalline Form B,
wherein Compound 2 has a structure of:
wherein the crystalline Form B is characterized by an X-ray powder diffraction (XRPD) pattern (i) having all of the following peaks 6.2, 12.6, 14.8, 19.0, and 19.8 degrees 2 theta, ±0.2°; and (ii) having at least one of the following peaks: 14.5, 17.8, 21.4, 26.3, 31.9 and 38.6 degrees 2 theta, ±0.2°.
7. The method of claim 6 , wherein the first solvent is methanol.
8. The method of claim 7 , wherein the anti-solvent is water.
9. The method of claim 8 , further comprising (3) stirring the mixture of Compound 2 in the first solvent and the anti-solvent to form a suspension; and (4) optionally filtering and drying the precipitated Compound 2 in crystalline Form B.
10. The method of claim 6 , wherein the crystalline Form B is characterized by an X-ray powder diffraction (XRPD) pattern having the following peaks: 6.2, 12.6, 13.6, 14.5, 14.8, 15.6, 17.8, 19.0, 19.8, 20.2, 21.4, 26.3, 31.9 and 38.6 degrees 2 theta, ±0.2°.
11. The method of claim 10 , wherein the crystalline Form B is characterized by an X-ray powder diffraction (XRPD) pattern that does not have one or both peaks at 7.3 and 14.2 degrees 2 theta, ±0.2°.
12. The method of claim 6 , wherein the crystalline Form B is characterized by a Differential Scanning calorimetry (DSC) pattern having an endothermic peak with an onset temperature of about 289.0° C. and/or peak temperature at about 290.1° C.
13. The Compound 2 in crystalline Form B produced by the method of claim 9 .
14. A method of preparing Compound 2 in crystalline Form B, the method comprising:
1) suspending Compound 2 in a crystalline form other than crystalline Form B in a solvent to form a suspension; and
2) stirring the suspension at room temperature or under heat to form Compound 2 in crystalline Form B,
wherein Compound 2 has a structure of:
wherein:
the crystalline Form B is characterized by an X-ray powder diffraction (XRPD) pattern (i) having all of the following peaks 6.2, 12.6, 14.8, 19.0, and 19.8 degrees 2 theta, ±0.2°; and (ii) having at least one of the following peaks: 14.5, 17.8, 21.4, 26.3, 31.9 and 38.6 degrees 2 theta, ±0.2°.
15. The method of claim 14 , wherein the Compound 2 in a crystalline form other than crystalline Form B is in crystalline Form A, which is characterized by an X-ray powder diffraction (XRPD) pattern (i) having the following peaks: 6.2, 12.6, 14.8, and 19.9 degrees 2 theta, ±0.2°; (ii) not having two or more of the following peaks: 7.3, 14.2, 15.7, and 16.3 degrees 2 theta, ±0.2°; and (iii) not having two or more of the following peaks: 14.5, 15.6, 20.2, and 38.6 degrees 2 theta, ±0.2°.
16. The method of claim 14 , wherein the solvent is methanol.
17. The method of claim 16 , wherein the concentration of the Compound 2 in the suspension ranges from 15-100 mg/ml.
18. The method of claim 15 , wherein the solvent is methanol.
19. The method of claim 18 , wherein the concentration of the Compound 2 in the suspension ranges from 15-100 mg/ml.
20. The Compound 2 in crystalline Form B produced by the method of claim 19 .