CRYSTALLINE SALT FORMS OF A 5,6,7,8-TETRAHYDRO-1,2,4-TRIAZOLO[4,3-a]PYRAZINE DERIVATIVE

Abstract

This invention provides novel crystalline acid salt forms of 7-[(3R)-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3-a]pyrazine, i.e. sitagliptin, to processes for their preparation and isolation, and to pharmaceutical compositions comprising the same.

1 . A crystalline acid salt form of sitagliptin, wherein said acid is selected from the group consisting of ethanedisulfonic acid, galactaric acid, thiocyanic acid, and glutaric acid. 
   
   
       2 . The crystalline acid salt form of sitagliptin of  claim 1 , wherein said crystalline acid salt form is sitagliptin ethanedisulfonate Form I, which shows an XRD pattern (2θ) (±0.2°) having characteristics peaks at 8.0, 13.8, 16.0, 18.0, 18.7, 19.6, 21.2, 21.4, 21.6, 22.7, 23.5, 24.4, 25.4, 25.6, and 27.1°. 
   
   
       3 . The sitagliptin ethanedisulfonate Form I of  claim 2 , which shows an XRD pattern (2θ) (±0.2°) having further peaks at 6.3, 6.6, 7.1, 11.2, 14.4, 20.4, 23.0, 24.8, 26.5, 27.9, and 34.7°. 
   
   
       4 . A process for preparing the sitagliptin ethanedisulfonate Form I of  claim 2 , said process comprising contacting sitagliptin base with ethanedisulfonic acid in the presence of a suitable solvent, and removing the solvent. 
   
   
       5 . A process for preparing the sitagliptin ethanedisulfonate Form I of  claim 3 , said process comprising contacting sitagliptin base with ethanedisulfonic acid in the presence of a suitable solvent, and removing the solvent. 
   
   
       6 . The process of  claim 4 , wherein the suitable solvent is a C 1 -C 5  alcohol solvent. 
   
   
       7 . The crystalline acid salt form of sitagliptin of  claim 1 , wherein said crystalline acid salt form is sitagliptin galactarate Form I, which shows an XRD pattern (2θ) (±) 0.2°) having characteristics peaks at 4.4, 13.2, 19.6, 22.4, and 30.7°. 
   
   
       8 . The sitagliptin galactarate Form I of  claim 7 , which shows an XRD pattern (2θ) (±0.2°) having further peaks at 14.3, 15.5, 16.5, 17.5, 18.6, 19.0, 23.0, 24.1, 25.4, 26.0, 26.9, 27.1, 34.5, and 37.7°. 
   
   
       9 . A process for preparing the sitagliptin galactarate Form I of  claim 7 , said process comprising contacting sitagliptin base with galactaric acid in the presence of a suitable solvent, and removing the solvent. 
   
   
       10 . A process for preparing the sitagliptin galactarate Form I of  claim 8 , said process comprising contacting sitagliptin base with galactaric acid in the presence of a suitable solvent, and removing the solvent. 
   
   
       11 . The process of  claim 9 , wherein the suitable solvent is a C 1 -C 5  alcohol solvent. 
   
   
       12 . The crystalline acid salt form of sitagliptin of  claim 1 , wherein said crystalline acid salt form is sitagliptin thiocyanate Form I, which shows an XRD pattern (2θ) (±) 0.2°) having characteristics peaks at 7.9, 13.7, 15.8, 17.7, 17.9, 19.4, 22.4, 22.5, 23.3, 25.2, 25.3, 26.9, 31.7, and 45.4°. 
   
   
       13 . The sitagliptin thiocyanate Form I of  claim 12 , which shows an XRD pattern (2θ) (±0.2°) having further peaks at 6.2, 26.5, and 27.3°. 
   
   
       14 . A process for preparing the sitagliptin thiocyanate Form I of  claim 12 , said process comprising contacting sitagliptin base with thiocyanic acid in the presence of a suitable solvent, and removing the solvent. 
   
   
       15 . A process for preparing the sitagliptin thiocyanate Form I of  claim 13 , said process comprising contacting sitagliptin base with thiocyanic acid in the presence of a suitable solvent, and removing the solvent. 
   
   
       16 . The process of  claim 14 , wherein the suitable solvent is a C 1 -C 5  alcohol solvent. 
   
   
       17 . The crystalline acid salt form of sitagliptin of  claim 1 , wherein said crystalline acid salt form is sitagliptin glutarate Form I, which shows an XRD pattern (2θ) (±0.2°) having characteristics peaks at 15.3, 16.3, 17.5, 18.0, 18.3, 20.7, 22.4, 22.8, 23.4, 24.6, and 25.4°. 
   
   
       18 . The sitagliptin glutarate Form I of  claim 17 , which shows an XRD pattern (2θ) (±0.2°) having further peaks at 6.3, 7.9, 9.4, 12.7, 12.8, 16.7, 19.9, 26.4, 27.8, 28.5, 28.6, 29.0, 30.5, and 33.8°. 
   
   
       19 . A process for preparing the sitagliptin glutarate Form I of  claim 17 , said process comprising contacting sitagliptin base with glutaric acid in the presence of a suitable solvent, and removing the solvent. 
   
   
       20 . A process for preparing the sitagliptin glutarate Form I of  claim 18 , said process comprising contacting sitagliptin base with glutaric acid in the presence of a suitable solvent, and removing the solvent. 
   
   
       21 . The process of  claim 19 , wherein the suitable solvent is a C 1 -C 5  alcohol solvent.