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

Temperature

60 °C

Tetrahydrofuran (10 mL) and 5 N aqueous sodium hydroxide solution (448 μL, 2.24 mmol) were added to 4-(5-(2-amino-pyridin-3-yl)-isoxazol-3-ylmethyl)-phenol (600 mg, 2.24 mmol) described in Manufacturing Example 5-1-1, which was irradiated by ultrasonic wave for 1 minute. The reaction solution was then concentrated under a reduced pressure to obtain a white solid. 2-Chloromethyl-5-fluoro-pyridine (359 mg, 2.46 mol) described in Manufacturing Example 41-2 and N,N-dimethylformamide (10 mL) were added to the resulting white solid and stirred for 1 hour at 60° C. After being cooled to room temperature, the reaction solution was partitioned into water and ethyl acetate. The organic layer was separated and concentrated under a reduced pressure. The residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1) to obtain the title compound (650 mg, 77%).

1. customwas irradiated by ultrasonic wave for 1 minute
2. concentrationThe reaction solution was then concentrated under a reduced pressure
3. customto obtain a white solid
4. additionwere added to the resulting white solid
5. temperatureAfter being cooled to room temperature
6. customthe reaction solution was partitioned into water and ethyl acetate
7. customThe organic layer was separated
8. concentrationconcentrated under a reduced pressure
9. customThe residue was purified by NH silica gel column chromatography (heptane:ethyl acetate=1:1)

ORD record

ord-19a082c15e42432fa8ea16e7e8a45532

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08153662B2