反应详情

A solution of 100 mg of 2-benzyl-1-oxo-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid, 168 mg of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride (2:1), 7.2 mg of hydroxybenzotriazole, 85 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 0.243 cm3 of N,N-diisopropylethylamine in 10 cm3 of dichloromethane is stirred at a temperature close to 20° C. for 20 h. Dichloromethane is added to the reaction medium. The organic phase is washed with water then with a saturated aqueous solution of sodium chloride, dried over sodium sulfate and concentrated using a rotary evaporator under reduced pressure (5 kPa). The 400 mg of product obtained are purified by flash chromatography over silica (column: 50 g; particle size: 15-40 μm; eluent: 100% ethyl acetate). After concentrating the fractions under reduced pressure, 103 mg of 2-benzyl-N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-1-oxo-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are obtained.

1. customclose to 20° C. for 20 h
2. washThe organic phase is washed with water
3. dry with materialwith a saturated aqueous solution of sodium chloride, dried over sodium sulfate
4. concentrationconcentrated
5. customa rotary evaporator under reduced pressure (5 kPa)