反应详情

To a solution of benzyl trans-4-fluoro-3-hydroxypiperidine-1-carboxylate (racemic) (0.486 g, 1.92 mmol) in dry THF (10 mL) at 0° C. was added NaH (0.126 g, 5.24 mmol) and the reaction was stirred at RT for 30 min. A solution of 5-bromo-3-(6-((4-methoxybenzyl)oxy)-2-(methylsulfonyl)pyrimidin-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (1 g, 1.74 mmol) in dry THF (5 mL) was added drop wise to the above mixture and the reaction was stirred for 2 h. The reaction was quenched with ice cold water (10 mL) and extracted with EtOAc (2×20 mL) and the combined organic layers were dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 35% EtOAc in petroleum ether) to give benzyl 3-((4-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-6-((4-methoxybenzyl)oxy)pyrimidin-2-yl)oxy)-(trans)-4-fluoropiperidine-1-carboxylate (racemic) (1 g, 77%) as a off white solid. MS (ESI, pos. ion) m/z: 745.7 (M+1).

1. stirringthe reaction was stirred for 2 h
2. customThe reaction was quenched with ice cold water (10 mL)
3. extractionextracted with EtOAc (2×20 mL)
4. customthe combined organic layers were dried
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified with silica gel chromatography (eluting with 35% EtOAc in petroleum ether)