反应详情

温度

90 °C

To a suspension of 6-({2-chloro-7-[(4-methylphenyl)sulfonyl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}amino)-2,3-difluorobenzamide (600 mg, 1.26 mmol) in 2,2,2-trifluoroethanol (40 ml) was added 1-[(dimethylamino)acetyl]-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinamine (366 mg, 1.39 mmol), hydrochloric acid as a 4.0M solution in dioxane (2.51 ml, 10.1 mmol), and catalytic potassium iodide (<10 mg). The resulting slurry was stirred at 90° C. in a pressure vial for 24 hours, at which time all solids had completely dissolved. The resulting solution was cooled to room temperature and diluted with dichloromethane and saturated sodium bicarbonate as to adjust the aqueous layer to pH>10. The organic layer was washed with water and a saturated brine solution, dried over sodium sulfate, filtered and solvents were removed under reduced pressure. The resulting green solid was purified via trituration with diethyl ether to afford 5-{[1-(N,N-dimethylglycyl)-6-(methyloxy)-1,2,3,4-tetrahydro-7-quinolinyl]amino}-8,9-difluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (830 mg, 1.21 mmol) as a yellow solid. (ESIMS (M+H)+=688)

1. dissolutionhad completely dissolved
2. temperatureThe resulting solution was cooled to room temperature
3. washThe organic layer was washed with water
4. dry with materiala saturated brine solution, dried over sodium sulfate
5. filtrationfiltered
6. customsolvents were removed under reduced pressure
7. customThe resulting green solid was purified via trituration with diethyl ether