反应详情

温度

0 °C

A solution of 3-[5-(2-chloro-6-methylpyridin-3-yl)-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl]-propionaldehyde (Prep109, 78 mg, 0.26 mmol), (1S,5R)-1-(4-trifluoromethyl-phenyl)-3-aza-bicyclo[3.1.0]hexane (Prep4, 60 mg, 0.26 mmol), and AcOH (19 μl) in dichloroethane (4 ml) was cooled to 0° C. NaBH(AcO)3 (58 mg, 0.26 mmol) was added portionwise. The mixture was stirred at 0° C. for further 2 hours and then basified with 1N NaOH. The product extracted with DCM, the organic phase was dried (Na2SO4) and evaporated. The residue was redissolved in DCM and stirred overnight in presence of PS-isocyanate. The mixture was filtered and the solvent was evaporated. The crude was purified by flash chromatography eluting with DCM-MeOH—NH4OH (98:2:0.2) and then was passed over a SCX cartridge to give 20 mg of the free base of title compound (15% yield).

1. extractionThe product 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 presence of PS-isocyanate
6. filtrationThe mixture was filtered
7. customthe solvent was evaporated
8. customThe crude was purified by flash chromatography
9. washeluting with DCM-MeOH—NH4OH (98:2:0.2)