反应详情

温度

0 °C

A solution of 3-[5-(2-fluoro-6-methyl-pyridin-3-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehyde (Prep117, 0.46 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 104 mg, 0.46 mmol), and AcOH (32 μl) in dichloroethane-MeOH (10-0.5, 4 ml) was cooled to 0° C. NaBH(AcO)3 (102 mg, 0.48 mmol) was added portionwise. The mixture was stirred at 0° C. for one hour and then basified with 1N NaOH. The product was extracted with DCM. The organic phase was dried (Na2SO4) and evaporated. The residue was redissolved in DCM and stirred overnight in the presence of PS-isocyanate (300 mg). The mixture was filtered and the solvent evaporated. The crude was purified by flash chromatography eluting with DCM-MeOH—NH4OH (98-2-0.2) and then SCX cartridge to give 90 mg of the title compound (40% yield).

1. extractionThe product was extracted with DCM
2. dry with materialThe organic phase was dried (Na2SO4)
3. customevaporated
4. dissolutionThe residue was redissolved in DCM
5. stirringstirred overnight in the presence of PS-isocyanate (300 mg)
6. filtrationThe mixture was filtered
7. customthe solvent evaporated
8. customThe crude was purified by flash chromatography
9. washeluting with DCM-MeOH—NH4OH (98-2-0.2)