Sodium Iodide → 3-(3-(4-Cyclopropylmethoxy-benzyl)-isoxazol-5-yl)-pyridin-2-ylamine

Temperature

60 °C

To a mixture of 4-(5-(2-amino-pyridin-3-yl)isoxazol-3-ylmethyl)-phenol (4.2 mg, 0.016 mmol) described in Manufacturing Example 5-1-1 and methanol (0.4 mL) was added 1 N aqueous sodium hydroxide solution (16 μL, 0.016 mmol), which was then concentrated under a reduced pressure. To a mixture of the residue and N,N-dimethylformamide (0.5 mL) were added cyclopropylmethyl bromide (2.3 μL, 0.019 mmol) and sodium iodide (1 mg, 7 μmol) at room temperature, which was stirred for 2 hours at 60° C. The reaction mixture was cooled to room temperature and then purified as is by reverse-phase high performance liquid chromatography (using an acetonitrile-water mobile phase containing 0.1% trifluoroacetic acid). The eluate was neutralized by triethylamine while being concentrated. The solvent was evaporated under a reduced pressure. The residue was washed with water to obtain the title compound (1.6 mg, 30%).

1. concentrationwas then concentrated under a reduced pressure
2. additionTo a mixture of the residue and N,N-dimethylformamide (0.5 mL)
3. temperatureThe reaction mixture was cooled to room temperature
4. custompurified
5. additioncontaining 0.1% trifluoroacetic acid)
6. concentrationwhile being concentrated
7. customThe solvent was evaporated under a reduced pressure
8. washThe residue was washed with water

ORD record

ord-3905d42170914bcc9016d0cc8369c7ce

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841327B2