Hydrochloride salts of 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy)-methyl]-8-phenyl-1,7-diaza-spiro[4.5]decan-2-one and preparation process therefor

1. A crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I):

wherein the crystalline Form I monohydrate hydrochloride salt form is characterized by an x-ray powder diffraction pattern including at least a strong peak having a diffraction angle (in 2Θ) of 21.6±0.2 and lattice spacing (in Å) of 4.11±0.04.

2. The crystalline Form I monohydrate hydrochloride salt form of claim 1 characterized by an x-ray powder diffraction pattern having at least one additional peak selected from

Diffraction

Lattice Spacing

angle (2Θ ± 0.2)

RI

(Å ± 0.04)

16.1

Medium

5.49 

18.4

Medium

4.83 

23.5

Medium

3.78.

3. The crystalline Form I monohydrate hydrochloride salt form of claim 1 characterized by an x-ray powder diffraction pattern having at least two additional peaks selected from

Diffraction angle

Lattice Spacing

(2Θ ± 0.2)

RI

(Å ± 0.04)

16.1

Medium

5.49

18.4

Medium

4.83

23.5

Medium

 3.78.

4. The crystalline Form I monohydrate hydrochloride salt form of claim 1 characterized by an x-ray powder diffraction pattern which includes the following peaks:

Diffraction angle

Lattice Spacing

(2Θ ± 0.2)

RI

(Å ± 0.04)

16.1

Medium

5.49

18.4

Medium

4.83

21.6

Strong

4.11

23.5

Medium

 3.78.

5. A crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I):

characterized by an x-ray powder diffraction pattern as shown in FIG. 1 .

6. A crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy)-methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I):

wherein the crystalline Form I monohydrate hydrochloride salt form is characterized by an infrared spectrum including at least a strong peak at 1167 cm −1 .

7. The crystalline Form I monohydrate hydrochloride salt form of claim 6 characterized by an infrared spectrum including at least one additional peak selected from 1693 cm −1 , 1277 cm −1 , 1141 cm −1 , 1130 cm −1 , 1094 cm −1 , 703 cm −1 and 682 cm −1 .

8. The crystalline Form I monohydrate hydrochloride salt form of claim 7 characterized by an infrared spectrum including at least two additional peaks selected from 1693 cm −1 , 1277 cm −1 , 1141 cm −1 , 1130 cm −1 , 1094 cm −1 , 703 cm −1 and 682 cm −1 .

9. The crystalline Form I monohydrate hydrochloride salt form of claim 7 characterized by an infrared spectrum including at least three additional peaks selected from 1693 cm −1 , 1277 cm −1 , 1141 cm −1 , 1130 cm −1 , 1094 cm −1 , 703 cm −1 and 682 cm −1 .

10. The crystalline Form I monohydrate hydrochloride salt form of claim 7 characterized by an infrared spectrum which includes the following peaks: 1693 cm −1 , 1277 cm −1 , 1167 cm −1 and 682 cm −1 .

11. A crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I):

characterized by an infrared spectrum as shown in FIG. 2 .

12. A crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy)-methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I):

wherein the crystalline Form I monohydrate hydrochloride salt form is characterized by a Raman spectrum including at least a weak peak at 3695 cm −1 .

13. The crystalline Form I monohydrate hydrochloride salt form of claim 12 characterized by a Raman spectrum including at least one additional peak selected from 3690 cm −1 , 3625 cm −1 , 1604 cm −1 , 1032 cm −1 , 997 cm −1 , 724 cm −1 and 616 cm −1 .

14. The crystalline Form I monohydrate hydrochloride salt form of claim 13 characterized by a Raman spectrum including at least two additional peaks selected from 3690 cm −1 , 3625 cm −1 , 1604 cm −1 , 1032 cm −1 , 997 cm −1 , 724 cm −1 and 616 cm −1 .

15. The crystalline Form I monohydrate hydrochloride salt form of claim 13 characterized by a Raman spectrum including at least three additional peaks selected from 3690 cm −1 , 3625 cm −1 , 1604 cm −1 , 1032 cm −1 , 997 cm −1 , 724 cm −1 and 616 cm −1 .

16. The crystalline Form I monohydrate hydrochloride salt form of claim 13 characterized by a Raman spectrum which includes the following peaks: 3695 cm −1 , 1032 cm −1 , 997 cm −1 and 724 cm −1 .

17. A crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I):

characterized by a Raman spectrum substantially as shown in FIG. 3 .

18. A crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy)-methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I):

wherein the crystalline Form I monohydrate hydrochloride salt form is characterized by a differential scanning calorimetric thermogram including at least an endotherm centered at approximately 101° C.

19. A crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I):

characterized by an differential scanning calorimetry thermogram substantially as shown in FIG. 4 .

20. A pharmaceutical composition comprising a crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy)-methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I):

according to claim 1 .

21. A pharmaceutical composition comprising a crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy)-methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I):

according to claim 6 .

22. A pharmaceutical composition comprising a crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy)-methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I):

according to claim 12 .

23. A pharmaceutical composition comprising a crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy)-methyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I):

according to claim 18 .