反应详情

温度

90 °C

A mixture of N-(5-bromo-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine (28.1 mg, 0.066 mmol), 5-fluoro-2-methoxypyridin-4-ylboronic acid (commercially available from Asymchem) (17.7 mg, 0.104 mmol), 2-dicyclohexylphosphino-2,6-dimethoxybiphenyl, (S-Phos) (5.9 mg, 0.014 mmol), palladium(II) acetate (5.1 mg, 7.57 μmol), and potassium phosphate tribasic (45.1 mg, 0.21 mmol) in DMF (1.0 mL) and water (0.05 mL) was degassed by nitrogen. The mixture was heated to 90° C. After 21.5 h, the reaction was cooled to rt, then treated with water. After extracting twice with EtOAc, the organic layers were combined and dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on basic alumina (0-35% EtOAc in hexanes) to afford an impure yellow residue. The light yellow film was further purified by HPLC (10-60% 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 bicarbonate solution and once with brine, the solvent was removed under reduced pressure to yield a white solid as N-(5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinyl)-5′-fluoro-2′-methoxy-3,4′-bipyridin-5-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.77 (1H, ddd, J=4.8, 1.8, 0.9 Hz), 8.43 (1H, t, J=1.7 Hz), 8.36 (1H, d, J=2.7 Hz), 8.09 (1H, d, J=2.2 Hz), 7.94 (2H, m), 7.66 (1H, ddd, J=9.6, 2.5, 1.4 Hz), 7.40 (1H, ddd, J=7.4, 4.8, 1.5 Hz), 7.11 (2H, m), 6.86 (1H, d, J=5.3 Hz), 3.95 (3H, s), 2.24 (3H, s). Mass Spectrum (pos.) m/e: 474.1 (M+1).

1. customwas degassed by nitrogen
2. temperaturethe reaction was cooled to rt
3. additiontreated 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 (0-35% EtOAc in hexanes)
8. customto afford an impure yellow residue
9. customThe light yellow film was further purified by HPLC (10-60% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution.) The desired fractions
10. concentrationwere concentrated
11. additionthen diluted with EtOAc
12. washAfter washing twice with satd aq. sodium bicarbonate solution and once with brine
13. customthe solvent was removed under reduced pressure