Tetrahydrofuran → 5-(3-(4-(5-Fluoro-pyridin-2-ylmethoxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine

Temperature

60 °C

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 the 2-chloromethyl-5-fluoro-pyridine (12.0 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 (3.0 mg, 11%).

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

ORD record

ord-3f4528da697748bd877da3e9074606ea

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158657B2