反应详情

温度

60 °C

To 4-(5-(2-amino-5-fluoro-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol (20.0 mg, 0.07 mmol) described in Manufacturing Example 174-1-1 were added tetrahydrofuran (3 mL) and a 5 N sodium hydroxide aqueous solution (14.0 μL, 0.07 mmol), which was dissolved by irradiating ultrasonic wave for 1 minute. Next, the reaction solution was concentrated under a reduced pressure, which gave a white solid. To a mixture of this solid and N,N-dimethylformamide (1 mL) was added an N,N-dimethylformamide (1 mL) solution of 2-chloromethyl-5-fluoro-pyridine (11.2 mg, 0.08 mmol) described in manufacturing Example 41-1-2, which was stirred for 1 hour at 60° C. The reaction mixture was cooled to room temperature and then partitioned into water and ethyl acetate. The organic layer was separated, washed with water and saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1) to obtain the title compound (24.7 mg, 89%).

1. customby irradiating ultrasonic wave for 1 minute
2. concentrationNext, the reaction solution was concentrated under a reduced pressure, which
3. customgave a white solid
4. temperatureThe reaction mixture was cooled to room temperature
5. custompartitioned into water and ethyl acetate
6. customThe organic layer was separated
7. washwashed with water and saturated aqueous sodium chloride
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under a reduced pressure
11. customthe residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1)