反应详情

4-(1H-1,2,3-Triazol-4-yl)butanoic acid (step 4) (882 mg, 4.95 mmol) and 3,5-dichlorobenzyl 4-aminopiperidine-1-carboxylate hydrochloride (step 2) (1.5 g, 4.95 mmol) were suspended in DMF (20 ml). DIPEA (4.32 ml, 24.74 mmol) was added and the reaction mixture stirred until all components were in solution. 50% T3P® solution in DMF (5.78 ml, 9.89 mmol) was added and the reaction mixture was stirred at RT for 48 hrs. The reaction mixture was diluted with EtOAc and washed twice with 10% citric acid. The aqueous citric acid wash was extracted with DCM (3×) and the combined extracted were dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography, using a gradient solvent system of 0-10% MeOH in EtOAc. The resulting product was further purified by stirring in diethyl ether over 72 hours. The mixture was filtered and the solid was dried in a vacuum oven to afford the title compound;

1. stirringthe reaction mixture was stirred at RT for 48 hrs
2. washwashed twice with 10% citric acid
3. washThe aqueous citric acid wash
4. extractionwas extracted with DCM (3×)
5. extractionthe combined extracted
6. dry with materialwere dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by flash chromatography
10. customThe resulting product was further purified
11. stirringby stirring in diethyl ether over 72 hours
12. filtrationThe mixture was filtered
13. customthe solid was dried in a vacuum oven