Reacción #165372

Ecuación de reacción

4-chloro-2-chloromethyl-pyridine

4-(5-(6-amino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol

tetrahydrofuran

sodium hydroxide

→

title compound

Rendimiento 26.2%

5-(3-(4-(4-Chloro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine

Rendimiento 26.2%

Disolventes

N,N-dimethylformamide

N,N-dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroby irradiating ultrasonic wave for 1 minute
2. 2
   ConcentraciónThe reaction solution was concentrated under a reduced pressure, which
3. 3
   Otrogave a white solid
4. 4
   workup.ADDITIONTo a mixture of the solid
5. 5
   TemperaturaThe reaction mixture was cooled to room temperature
6. 6
   Otropartitioned into water and ethyl acetate
7. 7
   OtroThe organic layer was separated
8. 8
   Lavadowashed with water and saturated aqueous sodium chloride
9. 9
   Secadodried over anhydrous magnesium sulfate
10. 10
    Filtraciónfiltered
11. 11
    ConcentraciónThe filtrate was concentrated under a reduced pressure
12. 12
    Otrothe residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1)

Procedimiento

To 4-(5-(6-amino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol (20.0 mg, 0.07 mmol) described in Manufacturing Example 177-1-1 were added tetrahydrofuran (3 mL) and a 5 N sodium hydroxide aqueous solution (14.9 μL, 0.07 mmol), which was dissolved by irradiating ultrasonic wave for 1 minute. The reaction solution was concentrated under a reduced pressure, which gave a white solid. To a mixture of the solid obtained above and N,N-dimethylformamide (1 mL) was added an N,N-dimethylformamide (1 mL) solution of 4-chloro-2-chloromethyl-pyridine (13.3 mg, 0.08 mmol) described in Manufacturing Example 51-1-2, 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 (7.2 mg, 25%).

Fuente