Patent ID: 8624026
Filing Date: 2014-01-07
Classification: A61K,A61P,C07D

Abstract:
1. A method of preparing sitagliptin of formula (I), which comprises the steps of: (i) allowing (S)-epichlorohydrin to undergo arylation, epoxidation, and vinylation reactions to obtain (2R)-1-(2,4,5-trifluorophenyl)-4-penten-2-ol of formula (II); (ii) azidatizing the compound of formula (II) to obtain (2S)-1-(2-azido-4-pentenyl)-2,4,5-trifluorobenzene of formula (III); (iii) oxidizing the compound of formula (III) to obtain (3R)-3-azido-4-(2,4,5-trifluorophenyl)-butyric acid of formula (IV); (iv) condensing the compound of formula (IV) with 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine hydrochloride of formula (VI) to obtain (3R)-3-azido-1-(3-trifluoromethyl)-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-4-(2,4,5-trifluorophenyl)-butan-1-one of formula (V); and (v) reducing the azido group of (3R)-3-azido-1-(3-trifluoromethyl)-5,6-dihyrdro-8H-[1,2,4]-triazolo[4,3-a]pyrazin-7-yl)-4-(2,4,5-trifluorophenyl)-butan-1-one of formula (V) to obtain sitagliptin of formula (I):