Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2h-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor

Abstract

Compositions comprising the succinate salt of 2-[6-(3-Amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethyl]-4-fluoro-benzonitrile (referred to herein as Compound I) which has the formula: wherein the Compound I is present in one or more polymorphic forms. Also provided are novel methods for the preparation of the polymorphs of Compound I, and kits and articles of manufacture of the compositions, and methods of using the compositions to treat various diseases.

1 - 10 . (canceled) 
     
     
         11 . A method for preparing Compound I of the formula 
       
         
           
           
               
               
           
         
         as polymorphic Form A characterized by one or more physical properties selected from the group consisting of: 
         (i) an X-ray powder diffraction pattern (CuKα) comprising diffraction peaks at about 11.31, 11.91, and 22.32 degree 2-theta (°2θ); 
         (ii) an X-ray powder diffraction pattern (CuKα) comprising diffraction peaks at about 11.31, 11.91, 19.26, 21.04, and 22.32°2θ; 
         (iii) a Raman spectrum comprising absorption bands expressed in reciprocal wavelengths at about 2954, 2935, 2225, 1698, 1659, and 1607 cm −1 ; 
         (iv) a Raman spectrum comprising absorption bands expressed in reciprocal wavelengths at about 3068, 2954, 2935, 2225, 1698, 1659, 1607, 1586, 1223, 1180, 901, 780, 751, 669, and 516 cm −1 ; 
         (v) an IR spectrum comprising absorption bands expressed in reciprocal wavelengths at about 3141, 2953, 2934, 2266, 1699, 1657, 1450, and 1206 cm −1 ; 
         (vi) an IR spectrum comprising absorption bands expressed in reciprocal wavelengths at about 3141, 2953, 2934, 2266, 2225, 1699, 1657, 1450, 1206, 886, 760, 685, 594, and 516 cm −1 ; and 
         (vii) a differential scanning calorimetry spectrum having an endotherm centered at about 193° C.; 
       
       comprising crystallizing Compound I from a solvent system selected from the group consisting of: acetone, acetonitrile, dichloromethane, 1,4-dioxane, dimethylformamide, ethylacetate, diethylether, hexane; isopropanol, tetrahydrofuran, toluene, trifluoroethanol, water, acetonitrile:water (85:15), ethanol:water (95:5), isopropanol:water (88:12), and tetrahydrofuran:water (9:1). 
     
     
         12 . A method for preparing Compound I as polymorphic Form A according to  claim 11 , comprising adding a miscible antisolvent to Compound I dissolved in a solvent, wherein the solvent/antisolvent are selected from the group consisting of dimethylformamide/acetonitrile, dimethylformamide/toluene, dimethylformamide/ethylacetate, dimethylformamide/isopropanol, methanol/acetonitrile, methanol/dichloromethane, trifluoroethanol/isopropanol, trifluoroethanol/acetonitrile, trifluoroethanol/ethylacetate, water/acetonitrile, and water/tetrahydrofuran. 
     
     
         13 - 27 . (canceled)