反应详情

Trifluoroacetic acid (1 mL) was added to a dichloromethane (1 mL) solution of the tert-butyl 4-({6-[5-(methylsulfonyl)indolin-1-yl]pyrimidin-4-yl}oxy)piperidine-1-carboxylate (188 mg, 0.396 mmol) produced in Example 1, and the mixture was stirred at room temperature for 2 hours. From the reaction solution, the solvent was distilled off under reduced pressure. To a dichloromethane (2.5 mL) solution of the obtained residue, isopropyl chloroformate (68 μL, 0.60 mmol) and triethylamine (276 μL, 1.98 mmol) were added at 0° C., and the mixture was stirred at room temperature. After 1.5 hours, isopropyl chloroformate (100 μL, 0.878 mmol) and triethylamine (410 μL, 2.94 mmol) were added to the reaction solution, and the mixture was further stirred for 1 hour. To the reaction solution, water was added, followed by extraction with ethyl acetate three times. The obtained organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [(i) hexane:ethyl acetate=70:30-50:50, V/V; (ii) ethyl acetate] to obtain the title compound as white powder (82.8 mg, yield: 45%).

1. distillationFrom the reaction solution, the solvent was distilled off under reduced pressure
2. stirringthe mixture was stirred at room temperature
3. waitAfter 1.5 hours
4. stirringthe mixture was further stirred for 1 hour
5. extractionfollowed by extraction with ethyl acetate three times
6. washThe obtained organic layer was washed with saturated saline
7. dry with materialdried over anhydrous magnesium sulfate
8. distillationthe solvent was distilled off under reduced pressure
9. customThe obtained residue was purified by silica gel column chromatography [(i) hexane:ethyl acetate=70:30-50:50, V/V; (ii) ethyl acetate]