反应详情

A mixture of 4-(benzyloxy)phenylboronic acid (3.53 g, 15.5 mmol), methyl 3-amino-2,6-dibromoisonicotinate (4.0 g, 12.9 mmol), tetrakis(triphenylphosphine)-palladium(0) (0.90 g, 0.77 mmol), sodium carbonate (3.28 g, 31.0 mmol) was flushed with nitrogen and toluene (32 mL), and MeOH (11 mL) were added. The reaction was heated at reflux under nitrogen for 24 hr. It was partitioned between EtOAc and water. The organic phase was washed with brine, dried with sodium sulfate and the solvent removed. Radial chromatography (step gradient elution with hexane containing 20 to 80% DCM) afforded methyl 3-amino-2-(4-(benzyloxy)phenyl)-6-bromoisonicotinate (3.28 g, 7.94 mmol, 62% yield) as a yellow solid. MS (ESI) m/z 415.0 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 7.77 (1H, s), 7.52-7.58 (2H, m), 7.41-7.46 (2H, m), 7.36-7.41 (2H, m), 7.30-7.36 (1H, m), 7.04-7.09 (2H, m), 5.95 (2H, br. s.), 3.92 (3H, s).

1. customwas flushed with nitrogen and toluene (32 mL), and MeOH (11 mL)
2. additionwere added
3. temperatureThe reaction was heated
4. temperatureat reflux under nitrogen for 24 hr
5. customIt was partitioned between EtOAc and water
6. washThe organic phase was washed with brine
7. dry with materialdried with sodium sulfate
8. customthe solvent removed
9. washRadial chromatography (step gradient elution with hexane containing 20 to 80% DCM)