Polymorphs

Abstract

The invention relates to polymorphous crystal modifications of a DPP-IV inhibitor, the preparation thereof and the use thereof for preparing a medicament.

1 . A method of preparing polymorph D of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, characterized in that it melts at 150±3° C., wherein polymorph D is obtained by heating polymorph C of the compound 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine to a temperature of 30-100° C. or by drying at this temperature, wherein Polymorph C is characterized in that it loses water at a temperature of 30-100° C. and exhibits further thermal effects at a temperature of about 150° C. and about 175° C. in a differential scanning calorimetry (DSC) analysis. 
     
     
         2 . The method according to  claim 1  wherein polymorph C is obtained by a method comprising:
 (a) refluxing a solution of 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in methanol to provide a hot methanolic solution, 
 (b) cooling the hot methanolic solution to a temperature of 40-60° C. to provide a cooled methanolic solution, 
 (c) adding tert-butylmethylether to the cooled methanolic solution to form a suspension, 
 (d) cooling the suspension first to a temperature of 15-25° C. and then to a temperature of 0-5° C. to provide crystals, 
 (e) suction filtering the crystals, and 
 (f) drying the crystals obtained in step (e) in vacuo at a temperature of 70° C. to provide Polymorph C. 
 
     
     
         3 . The method according to  claim 2 , wherein the X-ray powder diagram of Polymorph C has characteristic reflections at the following d values: 12.90 Å, 11.10 Å, 6.44 Å, 3.93 Å and 3.74 Å. 
     
     
         4 . The method according to  claim 2 , wherein the hot methanolic solution obtained in step (a) is filtered before cooling in step (b).