Crystalline forms of 8-(2-fluorobenzyl)-6-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyrazine as sGC stimulators

1. A crystalline Hydrate 2 of 8-(2-fluorobenzyl)-6-(3-(trifluoromethyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyrazine of the formula:

(i) wherein the crystalline Hydrate 2 is characterized by a powder X-ray diffraction pattern comprising at least three diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 10.4°±0.2 °2θ, 15.50±0.2 °2θ, 18.4°±0.2 °2θ, 18.7°±0.2 °2θ, and 21.9°±0.2 °2θ; or

(ii) wherein the crystalline Hydrate 2 is characterized by a powder X-ray diffraction pattern comprising at least three diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, and 27.6°±0.2 °2θ.

2. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is characterized by a powder X-ray diffraction pattern comprising at least three diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 10.4°±0.2 °2θ, 15.5°±0.2 °2θ, 18.4°±0.2 °2θ, 18.7°±0.2 °2θ, and 21.9°±0.2 °2θ.

3. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least four diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 10.4°±0.2 °2θ, 15.5°±0.2 °2θ, 18.4°±0.2 °2θ, 18.7°±0.2 °2θ, and 21.9°±0.2 °2θ.

4. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising diffraction peaks at diffraction angles (°2θ) of 10.4°±0.2 °2θ, 15.50±0.2 °2θ, 18.40±0.2 °2θ, 18.7°±0.2 °2θ, and 21.9°±0.2 °2θ.

5. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least six diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 10.4°±0.2 °2θ, 15.5°±0.2 °2θ, 18.4°±0.2 °2θ, 18.7°±0.2 °2θ, 20.7°±0.2 °2θ, 21.2°±0.2 °2θ, 21.9°±0.2 °2θ, 22.7°±0.2 °2θ, 24.6°±0.2 °2θ, 25.9°±0.2 °2θ, 26.3°±0.2 °2θ, and 27.4°±0.2 °2θ.

6. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least seven diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 10.4°±0.2 °2θ, 15.5°±0.2 °2θ, 18.4°±0.2 °2θ, 18.7°±0.2 °2θ, 20.7°±0.2 °2θ, 21.2°±0.2 °2θ, 21.9°±0.2 °2θ, 22.7°±0.2 °2θ, 24.6°±0.2 °2θ, 25.9°±0.2 °2θ, 26.3°±0.2 °2θ, and 27.4°±0.2 °2θ.

7. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least eight diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 10.4°±0.2 °2θ, 15.5°±0.2 °2θ, 18.4°±0.2 °2θ, 18.7°±0.2 °2θ, 20.7°±0.2 °2θ, 21.20±0.2 °2θ, 21.9°±0.2 °2θ, 22.7°±0.2 °2θ, 24.6°±0.2 °2θ, 25.9°±0.2 °2θ, 26.3°±0.2 °2θ, and 27.4°±0.2 °2θ.

8. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least nine diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 10.4°±0.2 °2θ, 15.5°±0.2 °2θ, 18.4°±0.2 °2θ, 18.7°±0.2 °2θ, 20.7°±0.2 °2θ, 21.2°±0.2 °2θ, 21.9°±0.2 °2θ, 22.7°±0.2 °2θ, 24.6°±0.2 °2θ, 25.9°±0.2 °2θ, 26.3°±0.2 °2θ, and 27.4°±0.2 °2θ.

9. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least ten diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 10.4°±0.2 °2θ, 15.5°±0.2 °2θ, 18.4°±0.2 °2θ, 18.7°±0.2 °2θ, 20.7°±0.2 °2θ, 21.2°±0.2 °2θ, 21.9°±0.2 °2θ, 22.7°±0.2 °2θ, 24.6°±0.2 °2θ, 25.9°±0.2 °2θ, 26.3°±0.2 °2θ, and 27.4°±0.2 °2θ.

10. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least eleven diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 10.4°±0.2 °2θ, 15.5°±0.2 °2θ, 18.4°±0.2 °2θ, 18.7°±0.2 °2θ, 20.7°±0.2 °2θ, 21.2°±0.2 °2θ, 21.9°±0.2 °2θ, 22.7°±0.2 °2θ, 24.6°±0.2 °2θ, 25.9°±0.2 °2θ, 26.3°±0.2 °2θ, and 27.4°±0.2 °2θ.

11. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising diffraction peaks at diffraction angles (°2θ) of 10.4°±0.2 °2θ, 15.50±0.2 °2θ, 18.4° 0.2 °2θ, 18.70±0.2 °2θ, 20.70±0.2 °2θ, 21.2°±0.2 °2θ, 21.9°±0.2 °2θ, 22.7°±0.2 °2θ, 24.6°±0.2 °2θ, 25.9°±0.2 °2θ, 26.3°±0.2 °2θ, and 27.4°±0.2 °2θ.

12. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is characterized by a powder X-ray diffraction pattern comprising at least three diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, and 27.6°±0.2 °2θ.

13. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least four diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, and 27.6°±0.2 °2θ.

14. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising diffraction peaks at diffraction angles (°2θ) of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, and 27.6°±0.2 °2θ.

15. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least six diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.2°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, 18.1°±0.2 °2θ, 18.70±0.2 °2θ, 19.0°±0.2 °2θ, 23.0°±0.2 °2θ, 24.80±0.2 °2θ, 25.1°±0.2 °2θ, 26.60±0.2 °2θ, 27.60±0.2 °2θ, and 29.80±0.2 °2θ.

16. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least seven diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.2°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, 18.1°±0.2 °2θ, 18.70±0.2 °2θ, 19.0°±0.2 °2θ, 23.0°±0.2 °2θ, 24.80±0.2 °2θ, 25.1°±0.2 °2θ, 26.6°±0.2 °2θ, 27.6°±0.2 °2θ, and 29.8°±0.2 °2θ.

17. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least eight diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.2°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, 18.1°±0.2 °2θ, 18.70±0.2 °2θ, 19.0°±0.2 °2θ, 23.0°±0.2 °2θ, 24.80±0.2 °2θ, 25.1°±0.2 °2θ, 26.6°±0.2 °2θ, 27.6°±0.2 °2θ, and 29.8°±0.2 °2θ.

18. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least nine diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.2°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, 18.1°±0.2 °2θ, 18.70±0.2 °2θ, 19.0°±0.2 °2θ, 23.0°±0.2 °2θ, 24.80±0.2 °2θ, 25.1°±0.2 °2θ, 26.60±0.2 °2θ, 27.6°±0.2 °2θ, and 29.8°±0.2 °2θ.

19. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least ten diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.2°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, 18.1°±0.2 °2θ, 18.70±0.2 °2θ, 19.0°±0.2 °2θ, 23.0°±0.2 °2θ, 24.80±0.2 °2θ, 25.1°±0.2 °2θ, 26.60±0.2 °2θ, 27.60±0.2 °2θ, and 29.80±0.2 °2θ.

20. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least eleven diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.2°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, 18.1°±0.2 °2θ, 18.70±0.2 °2θ, 19.0°±0.2 °2θ, 23.0°±0.2 °2θ, 24.80±0.2 °2θ, 25.1°±0.2 °2θ, 26.6°±0.2 °2θ27.6°±0.2° 2θ and 29.8°±0.2 °2θ.

21. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least twelve diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.2°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, 18.1°±0.2 °2θ, 18.70±0.2 °2θ, 19.0°±0.2 °2θ, 23.0°±0.2 °2θ, 24.80±0.2 °2θ, 25.1°±0.2 °2θ, 26.60±0.2 °2θ, 27.60±0.2 °2θ, and 29.80±0.2 °2θ.

22. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising at least thirteen diffraction peaks at diffraction angles (°2θ) selected from the group consisting of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.2°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, 18.1°±0.2 °2θ, 18.70±0.2 °2θ, 19.0°±0.2 °2θ, 23.0°±0.2 °2θ, 24.80±0.2 °2θ, 25.1°±0.2 °2θ, 26.6°±0.2 °2θ27.6°±0.2° 2θ and 29.8°±0.2 °2θ.

23. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a powder X-ray diffraction pattern comprising diffraction peaks at diffraction angles (°2θ) of 7.3°±0.2 °2θ, 10.6°±0.2 °2θ, 15.2°±0.2 °2θ, 15.8°±0.2 °2θ, 15.9°±0.2 °2θ, 18.1°±0.2 °2θ, 18.7°±0.2 °2θ, 19.0°±0.2 °2θ, 23.0°±0.2 °2θ, 24.8°±0.2 °2θ, 25.1°±0.2 °2θ, 26.6°±0.2 °2θ, 27.6°±0.2 °2θ, and 29.8°±0.2 °2θ.

24. The crystalline Hydrate 2 of claim 1 , wherein the diffraction peaks have a relative intensity of at least 10%.

25. The crystalline Hydrate 2 of claim 1 , wherein the diffraction peaks have a relative intensity of at least 15%.

26. The crystalline Hydrate 2 of claim 1 , wherein the diffraction peaks have a relative intensity of at least 20%.

27. The crystalline Hydrate 2 of claim 1 , wherein the diffraction peaks have a relative intensity of at least 25%.

28. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a differential scanning calorimetry (DSC) pattern as shown in FIG. 12 .

29. The crystalline Hydrate 2 of claim 1 , wherein the crystalline Hydrate 2 is further characterized by a thermal gravimetric analysis (TGA) pattern as shown in FIG. 13 .

30. A pharmaceutical composition comprising the crystalline Hydrate 2 of claim 1 and a pharmaceutically acceptable carrier or diluent.

31. A method for treating a central nervous system disorder in a patient in need thereof, wherein the method comprises the step of administering to the patient a therapeutically effective amount of the crystalline Hydrate 2 of claim 1 .