反应详情

温度

80 °C

To a suspension of methyl 6-amino-4-(4-bromo-2-chlorophenylamino)-5-chloronicotinate (966 mg, 2.48 mmol) in 13 ml DMF was added chloroacetaldehyde (50% aq. solution, 0.32 ml, 396 mg, 2.52 mmol) and the mixture was heated in a closed vessel to 80° C. for 3 h. The dark solution was cooled to room temperature and the DMF was removed by vacuum distillation. The residue was dissolved in THF and directly purified by column chromatography (EtOAc/hexanes 10:1+2% TEA) which delivered the desired product (638 mg, 62%). Rf (EtOAc/Hexanes 10:1)=0.4. 1H-NMR (500 MHz, MeOH-D3): δ=9.16 (s, 1H), 7.86-7.85 (d, 1H), 7.54-7.53 (d, 1H), 7.50-7.48 (d, 1H), 7.19-7.17 (dd, 1H), 6.51-6.50 (d, 1H), 3.82 (s, 3H).

1. temperatureThe dark solution was cooled to room temperature
2. customthe DMF was removed by vacuum distillation
3. dissolutionThe residue was dissolved in THF
4. customdirectly purified by column chromatography (EtOAc/hexanes 10:1+2% TEA) which