反应详情

30 mg (0.15 mmol) of 4-nitrophenyl chloroformate are added, at 0° C., to 57 mg (0.14 mmol) of 1-{1-[(R)-2-amino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidin-4-yl}butan-1-one (cf. preparation 2-3) dissolved in 2 ml of DCM. The reaction mixture is stirred for 4 hours at room temperature. The reaction is stopped by adding aqueous NH4OH solution and the organic compounds are extracted with DCM. The organic phase is then washed with water and dried over MgSO4, filtered and concentrated. The oil obtained is dissolved in DMF at 80° C., and 52 mg (0.28 mmol) of 2-(1H-[1,2,3]triazol-4-yl)ethylamine dihydrochloride and 0.1 ml (0.72 mmol) of triethylamine are then added. The reaction mixture is stirred at 80° C. for 10 minutes. After cooling to room temperature, dichloromethane is added and the organic phase is washed with 1N sodium hydroxide. The organic phase is dried over MgSO4, filtered and concentrated. The crude product obtained is chromatographed on silica gel (eluent: 93/7 DCM/MeOH). 25 mg of 1-[(R)-2-(4-butyryl-4-cyclohexylpiperidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-[2-(1H-[1,2,3]triazol-4-yl)ethyl]urea are obtained in the form of a white solid in a yield of 32%.

1. extractionthe organic compounds are extracted with DCM
2. washThe organic phase is then washed with water
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe oil obtained
7. stirringThe reaction mixture is stirred at 80° C. for 10 minutes
8. temperatureAfter cooling to room temperature
9. washthe organic phase is washed with 1N sodium hydroxide
10. dry with materialThe organic phase is dried over MgSO4
11. filtrationfiltered
12. concentrationconcentrated
13. customThe crude product obtained
14. customis chromatographed on silica gel (eluent: 93/7 DCM/MeOH)