反应详情

DIEA (0.47 mL), WSC (257 mg), and HOBT (181 mg) were added to a suspension of (E)-(S)-5-chloro-2-{1-[3-fluoro-4-(4-methyl-1H-imidazol-1-yl)phenyl]methylidene}-4-methylvaleric acid hydrochloride (250 mg) and (1R,2R)-1-amino-1-(3,4,5-trifluorophenyl)propan-2-ol hydrochloride (243 mg) in DMF (5 mL) at room temperature, and the reaction solution was stirred at room temperature for one hour. Ethyl acetate was added to the reaction solution, which was then sequentially washed with saturated sodium bicarbonate water, water, a saturated ammonium chloride solution, and brine. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was dissolved DMF (8 mL). 60% sodium hydride (32 mg) was added at 0° C., and the reaction solution was stirred at 0° C. for one hour. Ethyl acetate was added to the reaction solution, which was then sequentially washed with saturated sodium bicarbonate water, water, a saturated ammonium chloride solution, and brine. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) to obtain 176 mg of the title compound. The property values of the compound are as follows.

1. washwas then sequentially washed with saturated sodium bicarbonate water, water
2. dry with materialThe resulting organic layer was dried over magnesium sulfate
3. concentrationconcentrated under reduced pressure
4. dissolutionThe residue was dissolved DMF (8 mL)
5. addition60% sodium hydride (32 mg) was added at 0° C.
6. stirringthe reaction solution was stirred at 0° C. for one hour
7. additionEthyl acetate was added to the reaction solution, which
8. washwas then sequentially washed with saturated sodium bicarbonate water, water
9. dry with materialThe resulting organic layer was dried over magnesium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system)