反应详情

A mixture of 2,2′-Bis(diphenylphosphino)1,1′-binaphthyl [BINAP] (28.00 mg, 0.0451 mmol) and Palladium(II)acetate [Pd(OAc)2] (5.00 mg, 0.022 mmol) in dry toluene (3 ml) was stirred vigorously and nitrogen was bubbled through the suspension for 30 minutes. To this, 6-(5-amino-2-methylphenyl)-2-(4-(4-methylpiperazin-1-yl)phenylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one [45] (200 mg, 0.451 mmol), 1-bromoisoquinoline (112.60 mg, 0.541 mmol) and dry cesium carbonate (443.0 mg, 1.352 mmol) was added. Nitrogen was bubbled through for another 30 minutes; the mixture was allowed to 15 reflux overnight. The mixture was cooled, diluted with ethyl acetate, water was added and the layers separated. The aqueous layer was extracted with ethyl acetate and the two organic extracts were combined. The organics were washed with brine, then dried (sodiumsulfate), filtered and concentrated. Further purification by silica gel chromatography using 5-10% ethyl acetate/hexane as eluent provided 6-(5-(isoquinolin-1-ylamino)-2-methylphenyl)-2-(4-(4-methylpiperazin-1-yl)phenylamino)-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one [60] as a yellow solid [Yield: −223 mg, 87.0%].

1. customnitrogen was bubbled through the suspension for 30 minutes
2. customNitrogen was bubbled through for another 30 minutes
3. temperaturereflux overnight
4. temperatureThe mixture was cooled
5. additiondiluted with ethyl acetate, water
6. additionwas added
7. customthe layers separated
8. extractionThe aqueous layer was extracted with ethyl acetate
9. washThe organics were washed with brine
10. dry with materialdried (sodiumsulfate)
11. filtrationfiltered
12. concentrationconcentrated
13. customFurther purification by silica gel chromatography