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 . An isolated form of an anhydrous polymorph A 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, characterised in that it melts at 206±3° C., and further characterised in that it exhibits an X-ray powder diagram having inter alia characteristic reflexes at the following d values: 11.59 Å, 7.60 Å, 7.15 Å, 3.86 Å, 3.54 Å and 3.47. 
     
     
         2 . (canceled) 
     
     
         3 . An isolated form of an anhydrous polymorph B 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, characterised in that it exhibits an X-ray powder diagram having inter alia characteristic reflexes at the following d values: 11.25 Å, 9.32 Å, 7.46 Å, 6.98 Å and 3.77 Å. 
     
     
         4 - 13 . (canceled) 
     
     
         14 . The isolated form of polymorph A of  claim 1 , further characterised in that the reflex at 11.59 Å in the X-ray powder diagram has a relative intensity of 100% and further characterized in that the X-ray powder diagram exhibits no reflexes having a relative intensity of 1% or more at the following d values: 11.25 Å, 9.32 Å, 7.46 Å, and 6.98 Å. 
     
     
         15 . The isolated form of polymorph B of  claim 3 , further characterised in that the reflex at 11.3 Å in the X-ray powder diagram has a relative intensity of 100% and further characterized in that the X-ray powder diagram exhibits no reflexes having a relative intensity of 1% or more at the following d values: 11.59 Å, 7.60 Å, and 7.15 Å. 
     
     
         16 . An isolated form of an anhydrous polymorph B 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 according to  claim 3 , further characterised in that at a temperature of 10-40° C. it transforms reversibly into the polymorph A, said polymorph A characterised in that it melts at 206±3° C., and further characterised in that it exhibits an X-ray powder diagram having inter alia characteristic reflexes at the following d values: 11.59 Å, 7.60 Å, 7.15 Å, 3.86 Å, 3.54 Å and 3.47. 
     
     
         17 . Anhydrous polymorph A 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, said polymorph A characterised in that it melts at 206±3° C., and further characterised in that it exhibits an X-ray powder diagram having inter alia characteristic reflexes at the following d values: 11.59 Å, 7.60 Å, 7.15 Å, 3.86 Å, 3.54 Å and 3.47, unmixed with polymorph B, said polymorph B characterised in that it exhibits an X-ray powder diagram having inter alia characteristic reflexes at the following d values: 11.25 Å, 9.32 Å, 7.46 Å, 6.98 Å and 3.77 Å. 
     
     
         18 . Anhydrous polymorph B 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, said polymorph B characterised in that at a temperature of 10-40° C. it transforms reversibly into the polymorph A, and further characterised in that it exhibits an X-ray powder diagram having inter alia characteristic reflexes at the following d values: 11.25 Å, 9.32 Å, 7.46 Å, 6.98 Å and 3.77 Å, unmixed with polymorph A, said polymorph A characterised in that it exhibits an X-ray powder diagram having inter alia characteristic reflexes at the following d values: 11.59 Å, 7.60 Å, 7.15 Å, 3.86 Å, 3.54 Å and 3.47. 
     
     
         19 . An isolated form of an anhydrous polymorph A 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, characterised by its lattice metrics: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Symmetry: 
                   monocline 
                 
                     
                   spatial group: 
                   P 
                 
                     
                   a: 
                   16.16(2) Å 
                 
                     
                   b: 
                   17.02(1) Å 
                 
                     
                   c: 
                   18.18(2) Å 
                 
                     
                   β: 
                   100.95(6)° 
                 
                     
                   cell volume: 
                       4907(11) Å 3   
                 
                     
                     
                 
             
                
               
               
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         20 . An isolated form of an anhydrous polymorph B 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, characterised by its lattice metrics: 
       
         
           
                 
                 
                 
               
                     
                     
                 
                     
                   Symmetry: 
                   monocline 
                 
                     
                   spatial group: 
                   P2 1 /c (# 14) 
                 
                     
                   a: 
                   15.23(1) Å 
                 
                     
                   b: 
                   16.94(1) Å 
                 
                     
                   c: 
                   18.79(1) Å 
                 
                     
                   β: 
                   95.6(2)° 
                 
                     
                   cell volume: 
                        4823(3) Å 3