反应详情

温度

0 °C

To a solution of 3-[5-(6-Methyl-pyridin-3-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehyde (Prep59, 90 mg, 0.35 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 71 mg, 0.31 mmol) and AcOH (21 mg, 0.35 mmol) in dichloroethane (2 mL), NaBH(AcO)3 (77 mg, 0.36 mmol) was added portionwise at 0° C. The mixture was stirred at 0° C. for further 45 minutes, then a 1N solution of NaOH was added and the mixture extracted with EtOAc. The organic phase was dried and evaporated, the residue redissolved in DCM and treated with PS-isocyanate resin (400 mg) under stirring for 4 h. After filtration, the solvent was evaporated under vacuum, and the crude was purified by flash chromatography with DCM-MeOH—NH4OH (95-5-0.5) to give the title compound (65 mg, 40% yield) as free base.

1. extractionthe mixture extracted with EtOAc
2. customThe organic phase was dried
3. customevaporated
4. dissolutionthe residue redissolved in DCM
5. additiontreated with PS-isocyanate resin (400 mg)
6. stirringunder stirring for 4 h
7. filtrationAfter filtration
8. customthe solvent was evaporated under vacuum
9. customthe crude was purified by flash chromatography with DCM-MeOH—NH4OH (95-5-0.5)