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 stirred with heating at 90° C. overnight. The reaction was cooled to RT and filtered to remove insoluble material. The filtrate was diluted with THF and washed with brine (3×). The combined aqueous phases were extracted with THF (2×). The combined organics were washed with brine (1×), dried (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-yloxy)benzenamine (1.10 g, 83% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.30-8.29 (m, 1H), 8.22 (s, 1H), 7.92 (s, 1H), 7.12 (m, 1H), 7.00-6.98 (m, 1H), 6.72 (br s, 1H), 6.58-6.54 (m, 1H), 6.47-6.44 (m, 1H), 5.44 (s, 2H), 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 reaction 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 extracted with THF (2×)
9. washThe combined organics were washed with brine (1×)
10. dry with materialdried (MgSO4)
11. concentrationconcentrated in vacuo
12. custompurified by silica gel chromatography (MeOH/CHCl3)