Isopropanol → (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

온도

62.5 °C

In a 50 mL three neck flask IPA (5 mL) and Dibenzoyl-L-tartaric acid (1.75 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-94%) dissolved in methanol (6 mL) was added into reaction mixture at 60-65. 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 to 3 hrs. The salt was filtered and washed with a mixture of IPA: MeOH (2:1, 10 mL). An enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of 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.-1.08 g, % Y-29%, Purity by HPLC-99.1%, % Chiral purity by HPLC of R-isomer 76.7%).

1. additionwas added into reaction mixture at 60-65
2. customSolid salt was precipitated
3. temperatureIt was gradually cooled to room temperature over a period of 2 to 3 hrs
4. filtrationThe salt was filtered
5. washwashed with a mixture of IPA: MeOH (2:1, 10 mL)
6. additionAn enantiomerically enriched desired Dibenzoyl-L-tartaric acid salt of mixture of (2R)

ORD 기록

ord-7dbecd479f5a4b97b90160264c973a6b

출처 데이터셋

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08476437B2