反应详情

温度

150 °C

1-(3-Bromo-4-methoxyphenyl)-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amine (1.5 g, 3.12 mmol), pyrimidin-5-ylboronic acid (0.542 g, 4.37 mmol), [1,1′-bis (diphenylphosphino)ferrocene]palladium(II) chloride (0.128 g, 0.16 mmol) and aqueous potassium carbonate (2M, 4.69 mL, 9.37 mmol) were dissolved in DMF (14 mL). The resulting mixture was heated to 150° C. for 20 mins by microwaves. Methanol (20 mL) was added and the mixture concentrated in vacuo. Dichloromethane (40 mL), water (20 mL) and brine (5 mL) were added and the organic phase separated and evaporated directly on silica. The crude product was purified by gradient column chromatography (40 g silica column eluted with 0-10% [0.1M ammonia in methanol] in dichloromethane). The desired fractions were combined and evaporated to give 648 mg (43%) of the title compound.

1. concentrationthe mixture concentrated in vacuo
2. additionDichloromethane (40 mL), water (20 mL) and brine (5 mL) were added
3. customthe organic phase separated
4. customevaporated directly on silica
5. customThe crude product was purified by gradient column chromatography (40 g silica column eluted with 0-10% [0.1M ammonia in methanol] in dichloromethane)
6. customevaporated