Granted Patent B2

US 8,372,988 · App. 12/982,775 · Granted Feb 12, 2013

Abstract

Claims (22)

1. A polymorph of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine, Form I, having a solid state 13 C NMR spectrum comprising peaks at 149.7 and 141.0 ppm.

2. The polymorph of claim 1 , having a solid state 13 C NMR spectrum comprising peaks at 153.0, 149.7, 141.0, 27.6, and 13.9 ppm.

3. The polymorph of claim 2 , having a solid state 13 C NMR spectrum comprising peaks at 157.9, 153.0, 149.7, 141.0, 131.4, 33.8, 27.6, and 13.9 ppm.

4. The polymorph of claim 1 , having an IR spectrum comprising peaks at 1016 and 1223 cm −1 .

5. The polymorph of claim 4 , having an IR spectrum comprising peaks at 697, 870, 1016 and 1223 cm −1 .

6. The polymorph of claim 1 , having a Raman spectrum comprising peaks at 335 and 787 cm −1 .

7. The polymorph of claim 6 , having a Raman spectrum comprising peaks at 266, 293, 335, 653, 787 and 1497 cm −1 .

8. A polymorph of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine, Form I, having X-ray powder diffraction peaks expressed in degrees-2θ at 16.5 and 26.8.

9. The polymorph of claim 8 , having X-ray powder diffraction peaks expressed in degrees-2θ at 13.1, 16.5, 22.4 and 26.8.

10. The polymorph of claim 8 , having an IR spectrum comprising peaks at 1016 and 1223 cm −1 .

11. The polymorph of claim 10 , having an IR spectrum comprising peaks at 697, 870, 1016 and 1223 cm −1 .

12. The polymorph of claim 8 , having a Raman spectrum comprising peaks at 335 and 787 cm −1 .

13. The polymorph of claim 12 , having a Raman spectrum comprising peaks at 266, 293, 335, 653, 787 and 1497 cm −1 .

14. A polymorph of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine, Form I, having a Raman spectrum comprising peaks at 335 and 787 cm −1 .

15. The polymorph of claim 14 , having a Raman spectrum comprising peaks at 266, 293, 335, 653, 787 and 1497 cm −1 .

16. The polymorph of claim 1 , 8 , or 14 , substantially free of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine, Form II.

17. A form of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine comprising 50% or more by weight of Form I of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine of claim 1 , 8 , or 14 .

18. The form of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine of claim 17 comprising at least 55, 60, 65, 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99% by weight of Form I.

19. The form of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine of claim 17 , wherein the form is crystalline.

20. A method of producing a polymorph of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine comprising: heating [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine until formation of a liquid phase in a partial vacuum for a period; and cooling [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine to below the temperature at which the liquid phase is formed.

21. The method of claim 20 , wherein [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine is heated to about 70° C.

22. The method of claim 20 , wherein the polymorph of [3-(4-{2-butyl-1-[4-(4-chloro-phenoxy)-phenyl]-1H-imidazol-4-yl}-phenoxy)-propyl]-diethylamine comprises Form I.

Assignments (12)