反应详情

温度

0 °C

Add cold (ice bath) absolute EtOH (1 mL) slowly to a cooled 0° C. stirred mixture of (+/−)-5-[(3,5-bistrifluoromethyl-benzyl)-(3-oxo-butyryl)-amino]-8-chloro-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylic acid isopropyl ester (118 mg, 0.20 mmol) and phosphorus pentoxide (511 mg, 3.6 mmol). Then, add hydrazine hydrate (0.062 mL, 2.0 mmol) dropwise while keeping the mixture cooled at 0° C. Heat at 100° C. overnight in a sealed tube. Cool down the mixture and remove the solvents under reduce pressure. Partition the residue between water and dichloromethane. Separate the layers, and dry organic phase over anhydrous magnesium sulfate, filter and concentrate in vacuo. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, and then by a SCX cartridge to afford the title compound (25 mg, 21%). MS (ES+): 589 (M+H).

1. temperatureHeat at 100° C. overnight in a sealed tube
2. temperatureCool down the mixture
3. customremove the solvents
4. customPartition the residue between water and dichloromethane
5. customSeparate the layers, and dry organic phase over anhydrous magnesium sulfate
6. filtrationfilter
7. concentrationconcentrate in vacuo
8. customPurify the residue by flash chromatography
9. washeluting with hexanes/ethyl acetate