Sitagliptin → (3S)-3-Amino-1-(3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo(4,3-a)pyrazin-7(8H)-yl)-4-(2,4,5-trifluorophenyl)butan-1-one

Participants

Reaction Conditions

Reaction Steps

In a 50 mL three neck flask IPA (5 mL) and Dibenzoyl-L-tartaric acid monohydrate (1.84 g) were taken. It was heated to 60-65° C. 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (2.0 g, % purity-70%) dissolved in methanol (6 mL) was added into reaction mixture at 60-65° C. After 20 min. Dibenzoyl-L-tartaric acid salt of (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (20 mg, % Chiral purity by HPLC of R-isomer 99.6%) was added as a seeding. It was stirred for 60 min. at 60-65° C. Solid salt was precipitated. It was gradually cooled to room temperature over a period of 2-3 h. The salt was filtered and washed with a mixture of IPA: MeOH (2:1). An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of a mixture of (2R) and (2S)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine was obtained (Wt.-0.742 g, % Y-19.2%, Purity by HPLC-99.0%, % Chiral purity by HPLC of R-isomer 78.3%).

Provenance & Evidence