反应详情

温度

100 °C

A stirred mixture of N-(5-bromo-2-(2,2-dimethylmorpholino)pyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine (0.061 g, 0.11 mmol), 2-dicyclohexylphosphino-2′,4′,6′,-tri-i-propyl-1,1′-biphenyl (0.011 g, 0.023 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.011 g, 0.012 mmol), and sodium tert-butoxide (0.034 g, 0.35 mmol) in dry toluene (1.0 mL) was purged three times with argon and placed under vacuum three times. Before heating, morpholine (0.05 mL, 0.57 mmol) was added via syringe, then the mixture was heated to 100° C. After 21 h, the reaction was cooled to rt, then diluted with water and extracted three times with EtOAc. The organic extractions were combined and washed twice with brine. After drying over anhydrous sodium sulfate and filtration, the organic solvent was removed under reduced pressure. After dissolving in MeOH then syringe filtration, the mixture was purified with HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution). The desired fractions were concentrated then diluted with EtOAc. After washing twice with satd aq. sodium carbonate solution and once with brine, the solvent was removed under reduced pressure to yield N-(2-(2,2-dimethyl-4-morpholinyl)-5-(4-morpholinyl)-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, MeOH) δ ppm 8.71 (1H, d, J=5.1 Hz), 8.06 (1H, td, J=7.7, 1.8 Hz), 7.84 (1H, d, J=7.8 Hz), 7.64 (3H, m), 7.29 (1H, ddd, J=13.7, 9.0, 2.3 Hz), 6.53 (1H, d, J=2.7 Hz), 4.03 (7H, m), 3.16 (7H, m), 2.10 (3H, s), 1.41 (6H, m). Mass Spectrum ESI (pos.) m/e: 547.3 (M+H)+.

1. customwas purged three times with argon
2. temperatureBefore heating
3. temperaturethe reaction was cooled to rt
4. extractionextracted three times with EtOAc
5. extractionThe organic extractions
6. washwashed twice with brine
7. dry with materialAfter drying over anhydrous sodium sulfate and filtration
8. customthe organic solvent was removed under reduced pressure
9. dissolutionAfter dissolving in MeOH
10. filtrationsyringe filtration
11. customthe mixture was purified with HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution)
12. concentrationThe desired fractions were concentrated
13. additionthen diluted with EtOAc
14. washAfter washing twice with satd aq. sodium carbonate solution and once with brine
15. customthe solvent was removed under reduced pressure