Crystalline forms of a 3-[2-methanesulfonyl-1-(4-trifluoromethyl-phenoxy)ethyl]pyrrolidine compound

Abstract

The invention provides crystalline hydrochloride salts of (S)-3-[(S)-2-methanesulfonyl-1-(4-trifluoromethylphenoxy)ethyl]pyrrolidine. This invention also provides pharmaceutical compositions comprising the crystalline salts, processes and intermediates for preparing the crystalline salts, and methods of using the crystalline salts to treat diseases.

1 - 17 . (canceled) 
     
     
         18 . A method of treating a disease selected from pulmonary arterial hypertension, gastrointestinal disorders, cancer, rheumatoid arthritis, osteoarthritis, osteoporosis, and diabetes, comprising administering to a patient a therapeutically effective amount of a crystalline hydrochloride salt of (S)-3-[(S)-2-methanesulfonyl-1-(4-trifluoromethylphenoxy)ethyl]pyrrolidine; wherein the crystalline hydrochloride salt is selected from: (a) an anhydrous Form I, characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 5.37±0.20, 9.89±0.20, 10.28±0.20, 16.06±0.20, 16.66±0.20, 19.90±0.20, 21.46±0.20, 23.18±0.20, 26.88±0.20, and 27.28±0.20; (b) an anhydrous Form II, characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 7.14±0.20, 9.86±0.20, 11.38±0.20, 14.20±0.20, 15.64±0.20, 18.00±0.20, 21.38±0.20, 22.24±0.20, 30.20±0.20, and 36.36±0.20; and (c) a monohydrate, characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 11.54±0.20, 14.38±0.20, 14.96±0.20, 16.44±0.20, 18.30±0.20, 19.62±0.20, 21.56±0.20, 24.56±0.20, 25.06±0.20, 25.96±0.20, and 26.92±0.20. 
     
     
         19 . The method of  claim 18 , where the disease is pulmonary arterial hypertension. 
     
     
         20 . A method of treating a patient that is in need of anti-platelet therapy, comprising administering a therapeutically effective amount of a crystalline hydrochloride salt of (S)-3-[(S)-2-methanesulfonyl-1-(4-trifluoromethylphenoxy)ethyl]pyrrolidine; wherein the crystalline hydrochloride salt is selected from: (a) an anhydrous Form I, characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 5.37±0.20, 9.89±0.20, 10.28±0.20, 16.06±0.20, 16.66±0.20, 19.90±0.20, 21.46±0.20, 23.18±0.20, 26.88±0.20, and 27.28±0.20; (b) an anhydrous Form II, characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 7.14±0.20, 9.86±0.20, 11.38±0.20, 14.20±0.20, 15.64±0.20, 18.00±0.20, 21.38±0.20, 22.24±0.20, 30.20±0.20, and 36.36±0.20; and (c) a monohydrate, characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 11.54±0.20, 14.38±0.20, 14.96±0.20, 16.44±0.20, 18.30±0.20, 19.62±0.20, 21.56±0.20, 24.56±0.20, 25.06±0.20, 25.96±0.20, and 26.92±0.20.