Claims for Patent: 8,178,550

Summary for Patent: 8,178,550

Title:	Hydrochloride salts of 8-[{1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy)-methyl]-8-phenyl-1,7-diaz- a-spiro[4.5]decan-2-one and preparation process therefor
Abstract:	Disclosed are hydrochloride and tosylate crystalline salt forms of (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-methyl]-8-ph- enyl-1,7-diazaspiro[4.5]decan-2-one, represented by Formula I and methods of preparing the same.
Inventor(s):	Hu; Mengwei (Washington, NJ), Paliwal; Sunil (Monroe Township, NJ), Shih; Neng-Yang (Warren, NJ), Guenter; Frank Bruno (Schachen, CH), Mergelsberg; Ingrid (Mahwah, NJ)
Assignee:	OPKO Health, Inc. (Miami, FL)
Application Number:	11/732,548
Patent Claims:	1. A crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-met- hyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I): ##STR00006## 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 2.THETA.) of 21.6.+-.0.2 and lattice spacing (in .ANG.) 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 TABLE-US-00028 Diffraction Lattice Spacing angle (2.THETA. .+-. 0.2) RI (.ANG. .+-. 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 TABLE-US-00029 Diffraction angle Lattice Spacing (2.THETA. .+-. 0.2) RI (.ANG. .+-. 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: TABLE-US-00030 Diffraction angle Lattice Spacing (2.THETA. .+-. 0.2) RI (.ANG. .+-. 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}-met- hyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I): ##STR00007## 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)-met- hyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I): ##STR00008## wherein the crystalline Form I monohydrate hydrochloride salt form is characterized by an infrared spectrum including at least a strong peak at 1167 cm.sup.-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.sup.-1, 1277 cm.sup.-1, 1141 cm.sup.-1, 1130 cm.sup.-1, 1094 cm.sup.-1, 703 cm.sup.-1 and 682 cm.sup.-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.sup.-1, 1277 cm.sup.-1, 1141 cm.sup.-1, 1130 cm.sup.-1, 1094 cm.sup.-1, 703 cm.sup.-1 and 682 cm.sup.-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.sup.-1, 1277 cm.sup.-1, 1141 cm.sup.-1, 1130 cm.sup.-1, 1094 cm.sup.-1, 703 cm.sup.-1 and 682 cm.sup.-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.sup.-1, 1277 cm.sup.-1, 1167 cm.sup.-1 and 682 cm.sup.-1. 11. A crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-met- hyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I): ##STR00009## 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)-met- hyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I): ##STR00010## wherein the crystalline Form I monohydrate hydrochloride salt form is characterized by a Raman spectrum including at least a weak peak at 3695 cm.sup.-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.sup.-1, 3625 cm.sup.-1, 1604 cm.sup.-1, 1032 cm.sup.-1, 997 cm.sup.-1, 724 cm.sup.-1 and 616 cm.sup.-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.sup.-1, 3625 cm.sup.-1, 1604 cm.sup.-1, 1032 cm.sup.-1, 997 cm.sup.-1, 724 cm.sup.-1 and 616 cm.sup.-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.sup.-1, 3625 cm.sup.-1, 1604 cm.sup.-1, 1032 cm.sup.-1, 997 cm.sup.-1, 724 cm.sup.-1 and 616 cm.sup.-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.sup.-1, 1032 cm.sup.-1, 997 cm.sup.-1 and 724 cm.sup.-1. 17. A crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-met- hyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I): ##STR00011## 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)-met- hyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I): ##STR00012## 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.degree. C. 19. A crystalline Form I monohydrate hydrochloride salt form of the compound (5S,8S)-8-[{(1R)-1-(3,5-Bis-(trifluoromethyl)phenyl)-ethoxy}-met- hyl]-8-phenyl-1,7-diazaspiro[4,5]decan-2-one (formula I): ##STR00013## 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-ph- enyl-1,7-diazaspiro[4,5]decan-2-one (formula I): ##STR00014## 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-ph- enyl-1,7-diazaspiro[4,5]decan-2-one (formula I): ##STR00015## 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-ph- enyl-1,7-diazaspiro[4,5]decan-2-one (formula I): ##STR00016## 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-ph- enyl-1,7-diazaspiro[4,5]decan-2-one (formula I): ##STR00017## according to claim 18.