反应详情

温度

100 °C

A suspension of 2-amino-6-methoxy-N-methylbenzamide (2.48 g, 13.8 mmol), N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (2.63 g, 6.88 mmol), palladium(II) acetate (0.077 g, 0.34 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.398 g, 0.69 mmol) and cesium carbonate (4.48 g, 13.77 mmol) in dioxane (37 mL) was degassed with argon and stirred at 100° C. for 3 hours. The reaction mixture was concentrated to dryness, diluted with EtOAc (80 ml), washed with water (1×50 ml) and brine, dried over magnesium sulfate and concentrated to afford an oil. The crude product was purified by flash chromatography on silica gel eluting with EtOAc and then 3 to 8% MeOH in EtOAc. The solvent was evaporated to dryness to afford a foam which was dissolved in DCM (12 ml). A solid formed after a few minutes and this was filtered and dried to give the title compound as a white solid (1.570 g, 52.5%). 1H NMR spectrum (500 MHz, CDCl3): 2.15 (s, 3H), 2.97 (d, 3H), 3.79 (s, 3H), 3.91 (s, 3H), 5.99 (s, 1H), 6.32 (s, 1H), 6.56 (d, 1H), 7.05 (d, 1H), 7.20 (dd, 1H), 7.34 (s, 1H), 7.44 (q, 1H), 8.23 (s, 1H), 10.56 (s, 1H); Mass spectrum: ESI+435.

1. customwas degassed with argon
2. concentrationThe reaction mixture was concentrated to dryness
3. additiondiluted with EtOAc (80 ml)
4. washwashed with water (1×50 ml) and brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated
7. customto afford an oil
8. customThe crude product was purified by flash chromatography on silica gel eluting with EtOAc
9. customThe solvent was evaporated to dryness
10. customto afford a foam which
11. customA solid formed after a few minutes
12. filtrationthis was filtered
13. customdried