反应详情

温度

100 °C

To a solution of 0.5 g of 3-(4-tert-butylphenyl)-1-[(2-chloropyridin-4-yl)methyl]-5,5-dimethylimidazolidine-2,4-dione obtained in stage a) of Example 7 in 15 mL of dioxane are successively added, under argon, 285 mg of 5-amino-2-hydroxypyridine, 1.6 g of caesium carbonate, 90 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) [xantphos] and 29 mg of palladium diacetate. The reaction mixture is heated at 100° C. for 1 hour, filtered and concentrated under reduced pressure. The residue is successively purified by chromatography on a column of silica, eluting with a mixture of dichloromethane and methanol (95/5 by volume) followed by HPLC (gradient: water/acetonitrile containing 0.1% formic acid) to give 35 mg of 3-(4-tert-butylphenyl)-1-({2-[(6-hydroxypyridin-3-yl)amino]pyridin-4-yl}methyl)-5,5-dimethylimidazolidine-2,4-dione, the characteristics of which are as follows:

1. filtrationfiltered
2. concentrationconcentrated under reduced pressure
3. customThe residue is successively purified by chromatography on a column of silica
4. washeluting with a mixture of dichloromethane and methanol (95/5 by volume)