反应详情

温度

80 °C

Methyl 3-(7-bromoimidazo[1,2-a]pyridine-3-carboxamido)-4-fluorobenzoate (Intermediate 1A)(1.08 g, 2.75 mmol), TBD (0.383 g, 2.75 mmol) and (2-(4-methylpiperazin-1-yl)phenyl)methanamine (0.565 g, 2.75 mmol) in toluene (35 ml) were heated to 80° C. for 6 hrs. A further portion of TBD (0.06 g, 0.431 mmol) and (2-(4-methylpiperazin-1-yl)phenyl)methanamine (0.100 g, 0.487 mmol) were added and the mixture was heated at 80° C. overnight. TBD (0.06 g, 0.431 mmol) was added and heating continued at 110° C. overnight. Toluene was removed in vacuo and the resulting solid was partitioned between aqueous sodium bicarbonate solution and EtOAc. The organic portion was washed with sodium bicarbonate solution (2×50 ml) and concentrated in vacuo. The resulting oil was dissolved in MeOH and purified by chromatography on silica eluting with 0-10% MeOH in DCM. The fractions were combined and the solvent removed in vacuo. The resulting solid was recrystallised from EtOAc (50 ml) to afford the title compound;

1. additionTBD (0.06 g, 0.431 mmol) was added
2. temperatureheating
3. customToluene was removed in vacuo
4. customthe resulting solid was partitioned between aqueous sodium bicarbonate solution and EtOAc
5. washThe organic portion was washed with sodium bicarbonate solution (2×50 ml)
6. concentrationconcentrated in vacuo
7. dissolutionThe resulting oil was dissolved in MeOH
8. custompurified by chromatography on silica eluting with 0-10% MeOH in DCM
9. customthe solvent removed in vacuo
10. customThe resulting solid was recrystallised from EtOAc (50 ml)