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

Temperature

60 °C

To 4-(5-(2-amino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol (50.0 mg, 0.19 mmol) described in Manufacturing Example 5-1-1 were added tetrahydrofuran (3 mL) and a 5N aqueous sodium hydroxide solution (37.3 μL, 0.19 mmol), which was dissolved by irradiating ultrasonic wave for 1 minute. The reaction mixture was then concentrated under a reduced pressure to obtain a white solid. An N,N-dimethylformamide (1 mL) solution of 2-chloromethyl-thiazole (29.8 mg, 0.22 mmol) described in Manufacturing Example 88-1-2 was added to a suspension of this solid and N,N-dimethylformamide (2 mL), which was stirred for 1 hour 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 the residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1) to obtain the title compound (53.0 mg, 78%).

1. customby irradiating ultrasonic wave for 1 minute
2. concentrationThe reaction mixture was then concentrated under a reduced pressure
3. customto obtain 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. customthe residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1)

ORD record

ord-2445cf6c01e64be8b87918e1dbc08f14

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08153662B2