反应详情

温度

90 °C

3-Chloro-4-(2-chloropyridin-4-yloxy)benzenamine (0.89 g, 3.49 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-pyrazole (0.871 g, 4.19 mmol) and K2CO3 (1.302 g, 9.42 mmol) were combined in DME (6 mL)/H2O (7.5 mL) and the headspace was flushed with Ar for 10 min. Pd(Ph3P)4 (0.202 g, 0.174 mmol) was then added and the biphasic reaction was heated at 90° C. overnight. The mixture was cooled to RT and filtered to remove insoluble material. The filtrate was diluted with THF, washed with brine (3×) and the combined aqueous phases were back-extracted with THF (2×). The combined organics were washed with brine (1×), dried over MgSO4, concentrated in vacuo and purified by silica gel chromatography (MeOH/CHCl3) to afford 3-chloro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (1.10 g, 83%). 1H NMR (400 MHz, DMSO-d6): δ 8.30-8.29 (m, 1 H), 8.22 (s, 1 H), 7.92 (s, 1 H), 7.12 (m, 1 H), 7.00-6.98 (m, 1 H), 6.72 (br s, 1 H), 6.58-6.54 (m, 1 H), 6.47-6.44 (m, 1 H), 5.44 (s, 2 H), 3.84 (s, 3H); MS (ESI) m/z: 301.1 (M+H+): 303.0 (M+2+H+).

1. customthe headspace was flushed with Ar for 10 min
2. customthe biphasic reaction
3. temperatureThe mixture was cooled to RT
4. filtrationfiltered
5. customto remove insoluble material
6. additionThe filtrate was diluted with THF
7. washwashed with brine (3×)
8. extractionthe combined aqueous phases were back-extracted with THF (2×)
9. washThe combined organics were washed with brine (1×)
10. dry with materialdried over MgSO4
11. concentrationconcentrated in vacuo
12. custompurified by silica gel chromatography (MeOH/CHCl3)