反应详情

To 2.35 g (5.64 mmol) of ethyl 1-[(R)-2-amino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidine-4-carboxylate dissolved in 25 mL of DCM immersed in a bath of cold water are added 1.25 g (6.21 mmol) of 4-nitrophenyl chloroformate. After warming to room temperature, the reaction medium is stirred for 1 hour. 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 then dried over MgSO4, filtered and concentrated. The crude product obtained is dissolved in 25 mL of DMF at 80° C., and 0.70 g (6.3 mmol) of histamine is then added. After 15 minutes, the reaction is stopped by adding aqueous 1N sodium hydroxide solution and the organic compounds are extracted with DCM. The organic phase is dried over MgSO4, filtered and concentrated. The crude product obtained is chromatographed on silica gel (eluent: 86/14 DCM/MeOH). 1.48 g of ethyl 4-cyclohexyl-1-[(R)-2-{3-[2-(1H-imidazol-4-yl)ethyl]ureido}-3-(4-methoxyphenyl)propionyl]piperidine-4-carboxylate in the form of a white powder are obtained in a yield of 47%.

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 crude product obtained
7. waitAfter 15 minutes
8. extractionthe organic compounds are extracted with DCM
9. dry with materialThe organic phase is dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe crude product obtained
13. customis chromatographed on silica gel (eluent: 86/14 DCM/MeOH)