反应详情

16 μL of diisopropylethylamine and 10 mg (51 μmol) of 4-nitrophenyl chloroformate are added to 25 mg (47 μmol) of 1-{1-[(R)-2-amino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidin-4-yl}butan-1-one (cf. preparation 4.4) dissolved in 5 ml of DCM. The reaction mixture is stirred for 2 hours at room temperature. The reaction is stopped by adding water and the organic compounds are extracted with DCM. The organic phase is then dried over MgSO4, filtered and concentrated. The oil obtained is dissolved in 5 ml of DMF at 80° C., and 14 mg of 5-(1H-imidazol-4-yl)pentylamine bis(trifluoroacetate) are added. The reaction mixture is stirred at 80° C. for 5 minutes and for 18 hours at room temperature. The organic phase is washed with 1N sodium hydroxide, extracted with dichloromethane and then dried over MgSO4, filtered and concentrated. The crude product obtained is purified by preparative HPLC. 3 mg of ethyl 4-cyclohexyl-1-[(R)-2-{3-[5-(1H-imidazol-4-yl)pentyl]ureido}-3-(4-methoxy-phenyl)propionyl]piperidine-4-carboxylate are obtained in a yield of 10%.

1. extractionthe organic compounds are extracted with DCM
2. dry with materialThe organic phase is then dried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated
5. customThe oil obtained
6. stirringThe reaction mixture is stirred at 80° C. for 5 minutes and for 18 hours at room temperature
7. washThe organic phase is washed with 1N sodium hydroxide
8. extractionextracted with dichloromethane
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated
12. customThe crude product obtained
13. customis purified by preparative HPLC