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温度

0 °C

To a solution of 5-(1,3-dioxolan-2-yl)-2-fluoro-3′,5′-dimethoxybiphenyl-4-amine (1.9 g, 6.0 mmol) and triethylamine (3.0 mL, 21.4 mmol) in THF (20 mL) at 0° C. was added triphosgene (0.6 g, 2.0 mmol), and stirred at 0° C. for 0.5 hour. After that, ammonia in methanol (3 mL, 21 mmol, 7 mol/L) was added. The reaction was stirred at 0° C. for 30 mins and quickly warmed to ambient temperature. After stirred for additional 30 mins at room temperature, the reaction mixture was acidified with 4 mol/L HCl in dioxane (8.2 mL) to pH 2 and then stirred at room temperature for 1 hour. Then the resultant solution was concentrated and purified by silica gel column chromatography (dichloromethane/methanol=50/1 to 10/1) to afford the title compound (2.0 g, 99%) as a yellow solid. MS (ES+) C16H13FN2O3 requires: 300, found: 301 [M+H]+.

1. stirringThe reaction was stirred at 0° C. for 30 mins
2. temperaturequickly warmed to ambient temperature
3. stirringAfter stirred for additional 30 mins at room temperature
4. stirringstirred at room temperature for 1 hour
5. concentrationThen the resultant solution was concentrated
6. custompurified by silica gel column chromatography (dichloromethane/methanol=50/1 to 10/1)