反应详情

温度

60 °C

Twenty-five grams of 2,4-dichloro-6,7-dimethoxyquinazoline was suspended in 2.25 L of a mixed solution consisting of toluene:tetrahydrofuran:a 2 N sodium carbonate solution=1:1:1. To the reaction mixture was added 21.5 g of 3-aminophenyl boronic acid ½ sulfate, and the mixture was degassed, the atmosphere in the reaction vessel was replaced with nitrogen. To the reaction mixture was added 2.23 g of tetrakis(triphenylphosphine)palladium(0), followed by stirring at 60° C. under a nitrogen atmosphere. Eighteen hours after initiation of the reaction, 1.2 g of tetrakis(triphenylphosphine)palladium(0) was added to the reaction mixture, and the stirring was continued. Thirty hours later, 1.2 g of tetrakis(triphenylphosphine)palladium(0) was further added to the reaction mixture, and stirring was further continued. Forty-eight hours after initiation of the reaction, the reaction mixture was cooled, and it was then transferred into a separatory funnel, so as to separate an organic layer. The obtained organic layer was washed with 300 mL of brine, and was then dried over anhydrous magnesium sulfate. The desiccant was removed by passing it through 250 g of silica gel. The silica gel was washed with 1.5 L of ethyl acetate, and the obtained organic layers were combined and concentrated to dryness. The residue was triturated with 200 mL of ethyl acetate, and the obtained solid was then filtrated. The solid was washed with 100 mL of diethyl ether and 200 mL of a mixed solution consisting of n-heptane:ethyl acetate=1:1, and dried under aeration to yield 28.2 g of a target product. Yield: 92.5%

1. customthe mixture was degassed
2. additionTo the reaction mixture was added 2.23 g of tetrakis(triphenylphosphine)palladium(0)
3. customEighteen hours after initiation of the reaction, 1.2 g of tetrakis(triphenylphosphine)palladium(0)
4. additionwas added to the reaction mixture
5. stirringstirring
6. customForty-eight hours after initiation of the reaction
7. temperaturethe reaction mixture was cooled
8. customit was then transferred into a separatory funnel
9. customso as to separate an organic layer
10. washThe obtained organic layer was washed with 300 mL of brine
11. dry with materialwas then dried over anhydrous magnesium sulfate
12. customThe desiccant was removed
13. washThe silica gel was washed with 1.5 L of ethyl acetate
14. concentrationconcentrated to dryness
15. customThe residue was triturated with 200 mL of ethyl acetate
16. filtrationthe obtained solid was then filtrated
17. washThe solid was washed with 100 mL of diethyl ether and 200 mL of a mixed solution
18. dry with materialethyl acetate=1:1, and dried under aeration