Patent ID: 9409912
Filing Date: 2016-08-09
CPC Classification: C07D

Claim Text:
1. A process for the preparation of sitagliptin phosphate anhydrous of Formula (I′) or monohydrate of Formula (I), the process comprising: (a) coupling (3R)—N-(tert-butoxycarbonyl)-3-amino-4-(2,4,5-trifluorophenyl)butanoic acid of Formula (V), with 3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,2,4-triazolo-[4,3-a]pyrazine or its hydrochloride of Formula (IV), in the presence of a coupling agent O-benzotriazol-1-yl-1,1,3-tetramethyluronium tetrafluoroborate and a base in one or more first solvents to obtain (R)-tert-butyl 4-oxo-4-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluoro phenyl)butan-2-ylcarbamate of Formula (III); (b) deprotecting the compound of Formula (III) with an acid in one or more second solvents to obtain sitagliptin free base of Formula (II) by removal of solvent; and (c) treating the sitagliptin free base of Formula (II) with at least 1.4 mole equivalent of phosphoric acid in one or more of the second solvents and recovering sitagliptin phosphate anhydrous of Formula (I′) having more than 19.0% phosphate content by ion chromatography (IC); or (d) treating the sitagliptin free base of Formula (II) with at least 1.4 mole equivalent of phosphoric acid in one or more of the second solvents optionally in the presence of seed crystals and recovering sitagliptin phosphate monohydrate of Formula (I) having more than 18.0% phosphate content by IC.