Amine salts of a CRTH2 antagonist

1. A salt in a crystalline form, comprising ethylenediamine and {4,6-bis(dimethylamino)-2-(4-(4-(trifluoromethyl)benzamido)benzyl)pyrimidin-5-yl} acetic acid of Formula I:

wherein the crystalline form has an X-ray powder diffraction pattern with a peak expressed in two-theta at approximately 5.9°, 11.6°, 17.5° and 29.4°.

2. The salt of claim 1 , comprising of about two molar equivalents of the acid of Formula I and about one molar equivalent of ethylenediamine.

3. The salt of claim 1 , having an X-ray powder diffraction pattern substantially as shown in FIG. 2 .

4. The salt of claim 1 , having a differential scanning calorimetric thermogram substantially as shown in FIG. 3 .

5. The salt of claim 1 , having a DSC thermogram with an endotherm at a peak temperature of about 123° C. and an onset temperature of about 114° C.

6. The salt of claim 1 , having a DSC thermogram with an endotherm at a peak temperature of about 216° C. and an onset temperature of about 212° C.

7. The salt of claim 1 , having an aqueous solubility of about 6 mg/mL at 25° C.

8. A salt in a crystalline form, comprising piperazine and {4,6-bis(dimethylamino)-2-(4-(4-(trifluoromethyl)benzamido)benzyl)pyrimidin-5-yl}acetic acid of Formula I:

wherein the crystalline form has an X-ray powder diffraction pattern with a peak expressed in two-theta at approximately 10.7, 15.9, 22.3, or 24.0°.

9. The salt of claim 8 , comprising of about two molar equivalents of the acid of Formula I and about one molar equivalent of piperazine.

10. The salt of claim 8 , having an X-ray powder diffraction pattern substantially as shown in FIG. 7 .

11. The salt of claim 8 , having a differential scanning calorimetric thermogram substantially as shown in FIG. 8 .

12. The salt of claim 8 , having a DSC thermogram with an endotherm at a peak temperature of about 203° C. and an onset temperature of about 198° C.

13. The salt of claim 8 , having a DSC thermogram with an endotherm at a peak temperature of about 223° C. and an onset temperature of about 219° C.

14. The salt of claim 8 , having an aqueous solubility of about 5 mg/mL at 25° C.

15. A salt in a crystalline form, comprising benzathine and {4,6-bis(dimethylamino)-2-(4-(4-(trifluoromethyl)benzamido)benzyl)pyrimidin-5-yl}acetic acid of Formula I:

wherein the crystalline form has an X-ray powder diffraction pattern with a peak expressed in two-theta at approximately 8.0, 11.5, 16.0, 17.5, or 23.4°.

16. The salt of claim 15 , comprising of about two molar equivalents of the acid of Formula I and about one molar equivalent of benzathine.

17. The salt of claim 15 , having an X-ray powder diffraction pattern substantially as shown in FIG. 12 .

18. The salt of claim 15 , having a differential scanning calorimetric thermogram substantially as shown in FIG. 13 .

19. The salt of claim 15 , having a DSC thermogram with an endotherm at a peak temperature of about 156° C. and an onset temperature of about 154° C.

20. The salt of claim 15 , having an aqueous solubility of about 0.08 mg/mL at 25° C.

21. A salt in a crystalline form, comprising choline and {4,6-bis(dimethylamino)-2-(4-(4-(trifluoromethyl)benzamido)benzyl)pyrimidin-5-yl}acetic acid of Formula I:

wherein the crystalline form has an X-ray powder diffraction pattern with a peak expressed in two-theta at approximately 6.5, 19.6, 20.0, 21.9, or 26.1°.

22. The salt of claim 21 , comprising of about one molar equivalent of the acid of Formula I and about one molar equivalent of choline.

23. The salt of claim 21 , having an X-ray powder diffraction pattern substantially as shown in FIG. 16 .

24. The salt of claim 21 , having a differential scanning calorimetric thermogram substantially as shown in FIG. 17 .

25. The salt of claim 21 , having a DSC thermogram with an endotherm at a peak temperature of about 195° C. and an onset temperature of about 193° C.

26. The salt of claim 21 , having an aqueous solubility of about 24 mg/mL at 25° C.

27. A pharmaceutical composition comprising the salt of claim 1 , and a pharmaceutically acceptable carrier or excipient.

28. The pharmaceutical composition of claim 27 , wherein the composition is formulated for oral, nasal, bronchial, or topical administration.

29. The pharmaceutical composition of claim 27 , wherein the composition is formulated as a single dosage form.

30. A process for the preparation of the salt of claim 1 , comprising reacting {4,6-bis(dimethylamino)-2-(4-(4-(trifluoromethyl)benzamido)benzyl)-pyrimidin-5-yl}acetic acid with the amine in a solvent at a first predetermined temperature.

31. The process of claim 30 , further comprising precipitating the salt at a second predetermined temperature.

32. A process for the preparation of the salt of claim 1 , comprising the steps of:

(a) generating the amine salt by reacting {4,6-bis(dimethylamino)-2-(4-(4-(trifluoromethyl)benzamido)benzyl)pyrimidin-5-yl}acetic acid with the amine in a solvent at a first predetermined temperature; and

(b) precipitating the amine salt at a second predetermined temperature.

33. The process of claim 30 , wherein the first temperature is from about −10 to about 150° C.

34. The process of claim 30 , wherein the first temperature is from about 20 to 100° C.

35. The process of claim 31 , wherein the second temperature is from about −50 to 50° C.

36. The process of claim 31 , wherein the second temperature is from about −23 to 35° C.

37. The process of claim 30 , wherein the solvent is selected from the group consisting of methanol, ethanol, isopropanol, propanol, tetrahydrofuran, water, and mixtures thereof.

38. The process of claim 30 , wherein an anti-solvent is added in the precipitating step to effect precipitation.

39. The process of claim 38 , wherein the anti-solvent is selected from the group consisting of water, alkanes, ethers, aromatic hydrocarbons, and mixtures thereof.