反应详情

温度

40 °C

To a solution of 150 mg of (2R)-2-amino-N-[5-{3-[(2-chloropyridin-4-yl)methyl]-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl}-2-(trifluoromethoxy)phenyl]-2-phenylacetamide obtained in stage d) of Example 5a in 10 mL of dioxane are successively added, under argon, 30 mg of N,N-dimethylurea, 13 mg of (9,9-dimethyl-9H-xanthene-3,6-diyl)bis(diphenylphosphine) (Xantphos), 5 mg of palladium acetate and 280 mg of caesium carbonate. The reaction mixture is refluxed for 1 hour and then filtered, and the filtrate is concentrated under reduced pressure. The residue is taken up in 10 mL of dioxane, 5 mL of a 4N solution of hydrogen chloride in dioxane are then added and the reaction mixture is stirred at 40° C. for 1 hour. After concentrating under reduced pressure, the residue is purified by HPLC (gradient: water/acetonitrile containing 0.1% formic acid) to give 45 mg of ((2R)-2-amino-N-{5-[3-({2-[(dimethylcarbamoyl)amino]pyridin-4-yl}methyl)-4,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethoxy)phenyl}-2-phenylacetamide, the characteristics of which are as follows:

1. temperatureThe reaction mixture is refluxed for 1 hour
2. filtrationfiltered
3. concentrationthe filtrate is concentrated under reduced pressure
4. addition5 mL of a 4N solution of hydrogen chloride in dioxane are then added
5. concentrationAfter concentrating under reduced pressure
6. customthe residue is purified by HPLC (gradient: water/acetonitrile containing 0.1% formic acid)