反应详情

温度

100 °C

A mixture of N-(5-bromo-6′-methoxy-2,3′-bipyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine (142.1 mg, 0.27 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl, (X-Phos) (25.8 mg, 0.054 mmol), tris(dibenzylideneacetone)dipalladium (0) (25.1 mg, 0.027 mmol), morpholine (0.05 mL, 0.57 mmol), and sodium tert-butoxide (74.9 mg, 0.78 mmol) in dry toluene (5 mL) was degassed by nitrogen. The mixture was heated to 100° C. After 23 h, the reaction was cooled to rt then treated with water. After extracting twice with EtOAc, the organic layer was combined and dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on basic alumina (5-20% EtOAc in hexanes) to afford an impure orange residue that was further purified with SFC chromatography to afford a yellow solid as 5,7-difluoro-N-(6′-methoxymorpholino-2,3′-bipyridin-3-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.74 (2H, m), 8.10 (2H, m), 7.95 (2H, m), 7.61 (1H, d, J=9.6 Hz), 7.39 (1H, ddd, J=6.7, 4.8, 2.0 Hz), 7.01 (3H, m), 6.53 (1H, d, J=2.3 Hz), 4.07 (3H, m), 3.91 (4H, m), 3.24 (4H, m), 2.23 (3H, s). Mass Spectrum (pos.) m/e: 541.2 (M+1).

1. customwas degassed by nitrogen
2. temperaturethe reaction was cooled to rt
3. additionthen treated with water
4. extractionAfter extracting twice with EtOAc
5. dry with materialdried over anhydrous magnesium sulfate
6. filtrationAfter filtration and concentration
7. customthe residue was purified on basic alumina (5-20% EtOAc in hexanes)
8. customto afford an impure orange residue that
9. customwas further purified with SFC chromatography