反应详情

温度

80 °C

6-Amino-2,5-dichloropyrimidine-4-carboxylic acid methyl ester (888 mg, 4 mmol), 2-(4-chloro-2-fluoro-3-methoxyphenyl)-[1,3,2]-dioxaborinane (1.47 g, 6 mmol), bis(triphenylphosphine)palladium(II) dichloride (280 mg, 0.4 mmol), and cesium fluoride (1.21 g, 8 mmol) were combined in 8 mL of 1,2-dimethoxyethane and 8 mL of water. The reaction mixture was heated at 80° C. for 3 hours and the cooled reaction mixture was partitioned between ethyl acetate and water. The organic phase was washed with water, dried, and concentrated. The product was purified by column chromatography (ethyl acetate/hexane gradient) then purified again by column chromatography (methylene chloride/ethyl acetate gradient) to yield 6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxyphenyl) pyrimidine-4-carboxylic acid methyl ester (738 mg, 53.5% yield):

1. customthe cooled reaction mixture
2. customwas partitioned between ethyl acetate and water
3. washThe organic phase was washed with water
4. customdried
5. concentrationconcentrated
6. customThe product was purified by column chromatography (ethyl acetate/hexane gradient)
7. customthen purified again by column chromatography (methylene chloride/ethyl acetate gradient)