反应详情

To solid N-{3-[5-(2-chloro-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (1 g, 1.85 mmol) was added 3-ethoxy-3-oxopropylzinc bromide 0.5M solution in THF (31.5 ml, 15.77 mmol) at RT. Bis(tri-t-butylphosphine)palladium (0) (0.095 g, 0.186 mmol) was added to reaction mixture. The reaction was stirred at RT for several hours. The reaction was check by LCMS. The reaction mixture was quenched into sat'd NH4Cl and stirred for several hours. A white/grey ppt was filtered. The EtOAc was added to filtrate. The EtOAc was separed contained form the water layer. The water layer was rewashed with EtOAc and the organic extracts combined, dried over MgSO4, filtered, and concentrated to dryness to give an orange oil. The crude product was added to a silica gel column and eluted with EtOAc with DCM (20% to 60%) and collected fractions to obtain ethyl 3-{4-[4-(3-{[(2,6-difluorophenyl)sulfonyl]amino}-2-fluorophenyl)-2-(1,1-dimethylethyl)-1,3-thiazol-5-yl]-2-pyrimidinyl}propanoate (1.12 g, 64%). MS (ESI): 605 [M+H]+.

1. customThe reaction mixture was quenched into sat'd NH4Cl
2. stirringstirred for several hours
3. filtrationA white/grey ppt was filtered
4. additionThe EtOAc was added to filtrate
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated to dryness
8. customto give an orange oil
9. washeluted with EtOAc with DCM (20% to 60%)
10. customcollected fractions