反应详情

温度

0 °C

A solution of crude 2-ethyl-3-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)-6-nitropyridine (1.280 g, 3.93 mmol) in MeOH (15 mL) and THF (15 mL) was treated with NH4Cl (8.42 g, 157 mmol), cooled to 0° C., treated portion-wise with zinc dust (2.57 g, 39.3 mmol), warmed to RT as the cooling bath expired and stirred overnight. The mixture was diluted with EtOAc, the solids removed via filtration through diatomaceous earth, washed with warm 2:1 EtOAc/MeOH and the filtrate concentrated to dryness. The residue was treated with EtOAc, heated to reflux, cooled to RT and the solids removed via filtration. The filtrate was again treated with EtOAc, heated to reflux and the solid collected via hot filtration. The filtrate was concentrated to dryness, purified via silica gel chromatography (MeOH/EtOAc) and combined with the above-isolated solid to afford 6-ethyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-amine (929 mg, 80%). 1H NMR (400 MHz, DMSO-d6): δ 8.30 (d, J=5.8 Hz, 1 H), 8.22 (s, 1 H), 7.93 (s, 1 H), 7.18 (d, J=8.7 Hz, 1 H), 7.12 (d, J=2.4 Hz, 1 H), 6.51 (dd, J=5.7, 2.4 Hz, 1 H), 6.36 (d, J=8.7 Hz, 1 H), 5.97 (s, 2 H), 3.84-3.83 (m, 3 H), 2.39 (q, J=7.6 Hz, 2 H), 1.04 (t, J=7.5 Hz, 3 H); MS (ESI) m/z: 296.1 (M+H+).

1. temperaturewarmed to RT as the cooling bath
2. customthe solids removed via filtration through diatomaceous earth
3. washwashed
4. temperaturewith warm 2:1 EtOAc/MeOH
5. concentrationthe filtrate concentrated to dryness
6. additionThe residue was treated with EtOAc
7. temperatureheated
8. temperatureto reflux
9. temperaturecooled to RT
10. customthe solids removed via filtration
11. additionThe filtrate was again treated with EtOAc
12. temperatureheated
13. temperatureto reflux
14. filtrationthe solid collected via hot filtration
15. concentrationThe filtrate was concentrated to dryness
16. custompurified via silica gel chromatography (MeOH/EtOAc)