HOAt → HCID 25206778, compound

Participants

Reaction Steps

Added to a solution of 171 mg of 7-(2-cyanophenyl)-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxylic acid in 2 cm3 of anhydrous dimethylformamide and under an argon atmosphere are 0.198 cm3 of triethylamine and 207 mg of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)butan-2-ol hydrochloride, then 71 mg of 1-hydroxy-7-azabenzotriazole and 100.5 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The solution is kept stirring for 15 h at a temperature close to 20° C. 50 cm3 of water and 50 cm3 of ethyl acetate are added to the reaction medium. After decanting, the organic phase is washed with 50 cm3 of a saturated aqueous solution of ammonium chloride, two lots of 20 cm3 of water, then 20 cm3 of a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure (5 kPa). The residual solution (around 3 cm3) is purified by flash chromatography over silica (column: 15 g; spherical silica of BP-SUP type, particle size: 20-40 μm; eluent: 50% heptane/50% ethyl acetate). After concentrating the fractions under reduced pressure, 268 mg of N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-7-(2-cyanophenyl)-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide are obtained in the form of a white powder.

Provenance & Evidence