反应详情

温度

100 °C

To the product from Step 1 (900 mg, 2.87 mmol) and Intermediate 22 (836 mg, 2.87 mmol) in dioxane (28 mL) was added palladium acetate (129 mg, 0.574 mmol), XantPhos (498 mg, 0.860 mmol) and cesium carbonate (1.87 g, 5.74 mmol). The mixture was degassed with Ar for 10 min and then heated at 100° C. for 20 h. After cooling to ambient temperature, the reaction mixture was filtered through celite and washed with ethyl acetate and methanol. After solvent removal, the residue was purified by column chromatography on silica gel (0-90%, ethyl acetate: 10:1 methanol in hexanes) to afford tert-butyl 4-{[2-({3-[2-(1-hydroxycyclobutyl)-1,3-thiazol-5-yl]-5-nitrophenyl}amino)pyrimidin-4-yl]oxy}piperidine-1-carboxylate (1.15 g, 2.02 mmol, 70%). MS ESI: [M+H]+ m/z 569.2.

1. customThe mixture was degassed with Ar for 10 min
2. temperatureAfter cooling to ambient temperature
3. filtrationthe reaction mixture was filtered through celite
4. washwashed with ethyl acetate and methanol
5. customAfter solvent removal
6. customthe residue was purified by column chromatography on silica gel (0-90%, ethyl acetate: 10:1 methanol in hexanes)