Crystalline form of (S)-(2-(6-chloro-7-methyl-1H-benzo[D]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone and its use as orexin receptor antagonists

1. A crystalline form of the compound (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone comprising:

the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 8.6°, 11.5°, 13.4°, 14.6°, 15.2°, 15.5°, 19.3°, 21.3°, 22.4°, and 26.4°; or

the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 10.9°, 13.4°, 14.3°, 14.9°, 18.3°, 20.9°, 21.1°, 21.8°, 24.0°, and 30.1°.

2. A crystalline form of the compound (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone according to claim 1 , comprising peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: θ: 8.6°, 11.5°, 13.4°, 14.6°, 15.2°, 15.5°, 19.3°, 21.3°, 22.4°, and 26.4°; wherein said X-ray powder diffraction diagram is obtained by using combined Cu Kα1 and Kα2 radiation, without Kα2 stripping; and the accuracy of the 2θ values is in the range of 2θ+/−0.2°.

3. A crystalline form of the compound (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone according to claim 2 , which shows the X-ray powder diffraction pattern as depicted in FIG. 2 .

4. A crystalline form of the compound (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone according to claim 2 , obtainable by:

a) mixing 2 g of COMPOUND as amorphous material with 8 mL of an ethanol/water mixture with volume/volume ratio of 1/4;

b) adding about 0.05 g seed crystals of COMPOUND in crystalline form 1;

c) shaking at 300 rpm for about 16 hours at room temperature;

d) filtering and washing the cake with 2 mL ethanol/water 1/4 (v/v) and drying the product at room temperature and reduced pressure of about 10 mbar for 4 hours; and

e) open equilibration at room temperature and about 60% relative humidity for 2 hours.

5. A crystalline form of the compound (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone according to claim 1 , comprising peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 10.9°, 13.4°, 14.3°, 14.9°, 18.3°, 20.9°, 21.1°, 21.8°, 24.0°, and 30.1°; wherein said X-ray powder diffraction diagram is obtained by using combined Cu Kα1 and Kα2 radiation, without Kα2 stripping; and the accuracy of the 20 values is in the range of 20+/−0.2°.

6. A crystalline form of the compound (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone according to claim 5 , which shows the X-ray powder diffraction pattern as depicted in FIG. 3 .

7. A crystalline form of the compound (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone according to claim 5 , obtainable by:

a) mixing 10 mg of COMPOUND in crystalline form 1 in 0.05 mL acetonitrile;

b) stirring in a closed 4 mL vial for up to three days;

c) isolating; and drying at reduced pressure and room temperature for 2 hours.

8. A pharmaceutical composition comprising as active ingredient a crystalline form of the compound (S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone according to claim 1 , and at least one pharmaceutically acceptable carrier.

9. A method of treatment of sleep disorders or anxiety disorders; comprising administering to a patient an effective amount of a crystalline form of the compound(S)-(2-(6-chloro-7-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5-methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone according to claim 1 .

10. The method of claim 9 , wherein the sleep disorders are selected from the group consisting of dyssomnias, parasomnias, sleep disorders associated with a general medical condition and substance-induced sleep disorders.

11. A method of treatment of sleep disorders or anxiety disorders; comprising administering to a patient an effective amount of a pharmaceutical composition according to claim 8 .

12. The method of claim 11 , wherein the sleep disorders are selected from the group consisting of dyssomnias, parasomnias, sleep disorders associated with a general medical condition and substance-induced sleep disorders.