反应详情

温度

90 °C

9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (34.1 mg, 0.06 mmol), palladium(II) acetate (7.93 mg, 0.04 mmol), 2-amino-N,6-dimethoxybenzamide (131 mg, 0.67 mmol), N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (150 mg, 0.39 mmol) and cesium carbonate (256 mg, 0.79 mmol) were weighed out in a microwave vial, sealed and dioxane (5 mL) was added. Argon was bubbled through the mixture for 5 minutes. The reaction was stirred at 90° C. overnight. The reaction mixture was allowed to cool to room temperature, diluted with DCM and MeOH. Silica gel was added and the mixture was concentrated. The crude product was purified by flash chromatography on silica gel (25 g) eluting with 0 to 5% MeOH in EtOAc/DCM (1:1). The solvent was evaporated to dryness. The residue was triturated in Et2O and the resulting precipitate was collected by filtration, washed with Et2O and dried to a constant weight to afford the title compound (131 mg, 74.1%) as a off-white solid. NMR Spectrum: (DMSOd6) 2.04 (s, 3H), 3.62 (s, 3H), 3.69 (s, 3H), 3.81 (s, 3H), 6.31 (bs, 1H), 6.89 (d, 1H), 7.06 (d, 1H), 7.43 (dd, 1H), 7.79 (s, 1H), 7.86 (s, 1H), 8.14 (s, 1H), 8.38 (s, 1H), 11.38 (s, 1H); Mass spectrum: MH+ 451.

1. customsealed
2. customArgon was bubbled through the mixture for 5 minutes
3. temperatureto cool to room temperature
4. additiondiluted with DCM and MeOH
5. additionSilica gel was added
6. concentrationthe mixture was concentrated
7. customThe crude product was purified by flash chromatography on silica gel (25 g)
8. washeluting with 0 to 5% MeOH in EtOAc/DCM (1:1)
9. customThe solvent was evaporated to dryness
10. customThe residue was triturated in Et2O
11. filtrationthe resulting precipitate was collected by filtration
12. washwashed with Et2O
13. customdried to a constant weight