反应详情

1.24 g (3 mmol) of 1-{1-[(R)-2-amino-3-(4-methoxyphenyl)propionyl]-4-cyclohexyl-piperidin-4-yl}butan-1-one and 660 mg (3.3 mmol) of para-nitrophenyl chloroformate are dissolved in 40 mL of dichloromethane at 0° C. The reaction mixture is stirred for 1 hour at room temperature and the reaction is then stopped by adding 20% aqueous ammonia solution and the organic products are extracted with dichloromethane. The organic phase is washed with water and then dried over sodium sulfate, filtered and concentrated. The white solid obtained is dissolved in 20 mL of DMF, the mixture is heated to 80° C., 0.367 g (3.3 mmol) of histamine is 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 NaOH solution and the reaction medium is extracted with DCM. The organic phase is washed with water and then dried over sodium sulfate, filtered and concentrated. The crude product obtained is chromatographed on silica gel (eluent: 80/20 DCM/MeOH). 1.1 g of 1-[(R)-2-(4-butyryl-4-cyclo-hexylpiperidin-1-yl)-1-(4-methoxybenzyl)-2-oxoethyl]-3-[2-(1H-imidazol-4-yl)ethyl]urea in the form of a white powder are obtained in a yield of 67%.

1. extractionthe organic products are extracted with dichloromethane
2. washThe organic phase is washed with water
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customThe white solid 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. extractionthe reaction medium is extracted with DCM
10. washThe organic phase is washed with water
11. dry with materialdried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated
14. customThe crude product obtained
15. customis chromatographed on silica gel (eluent: 80/20 DCM/MeOH)