反应详情

75 mg (0.18 mmol) of 1-{1-[(R)-2-amino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidin-4-yl}butan-1-one and 40 mg (0.2 mmol) of para-nitrophenyl chloroformate are dissolved in 5 ml of dichloromethane. The mixture is stirred for 1 hour at room temperature and the solution is then stopped by adding 20% aqueous ammonia and extracted with dichloromethane. The organic phase is washed with water and then dried over sodium sulfate, filtered and concentrated to dryness. The oil obtained is diluted in 5 ml of DMF, the mixture is heated to 80° C. and 39 mg (0.2 mmol) of 1-methylhistamine and 0.05 ml (0.36 mmol) of triethylamine are then added, and the solution is stirred for 5 minutes at 80° C. and for 10 minutes at room temperature. The reaction is stopped by adding aqueous 1N sodium hydroxide solution and then extracted with DCM. The organic phase is washed with water and then dried over sulfate, filtered and concentrated. The oil obtained is chromatographed on silica gel (eluent: 90/10 DCM/MeOH). 40 mg of 1-[(R)-2-(4-butyryl-4-cyclohexylpiperidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-[2-(1-methyl-1H-imidazol-4-yl)ethyl]urea in the form of a colourless oil are obtained in a yield of 39%.

1. extractionextracted with dichloromethane
2. washThe organic phase is washed with water
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated to dryness
6. customThe oil obtained
7. temperaturethe mixture is heated to 80° C.
8. stirringthe solution is stirred for 5 minutes at 80° C. and for 10 minutes at room temperature
9. extractionextracted with DCM
10. washThe organic phase is washed with water
11. dry with materialdried over sulfate
12. filtrationfiltered
13. concentrationconcentrated
14. customThe oil obtained
15. customis chromatographed on silica gel (eluent: 90/10 DCM/MeOH)