Tetrahydrofuran → 3-(3-(4-(3-Methoxy-benzyloxy)-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine

Temperature

60 °C

To 4-(5-(2-amino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol (30 mg, 0.11 mmol) described in Manufacturing Example 5-1-1 were tetrahydrofuran (3 mL) and a 5N sodium hydroxide aqueous solution (22.4 μL, 0.11 mmol), which was dissolved by irradiating ultrasonic wave for 1 minute. The reaction solution was then concentrated under a reduced pressure, which gave a white solid. To a suspension of this solid in N,N-dimethylformamide (1 mL) was added an N,N-dimethylformamide (1 mL) solution of 3-methoxybenzyl chloride (21.0 mg, 0.13 mmol), which was stirred for 12 hours at 60° C. This mixture was cooled to room temperature and 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 this residue was purified by NH silica gel column chromatography (heptane: ethyl acetate=1:1) to obtain the title compound (35.1 mg, 81%).

1. customby irradiating ultrasonic wave for 1 minute
2. concentrationThe reaction solution was then concentrated under a reduced pressure, which
3. customgave a white solid
4. temperatureThis 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. customthis residue was purified by NH silica gel column chromatography (heptane: ethyl acetate=1:1)

ORD record

ord-cadcac06f8214b62aa37d69cfb86c3c2

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841327B2