反应详情

A mixture of compound 17a (0.23 g, 0.57 mmol) and 2-bromoquinoline (1.0 g, 4.8 mmol) in a vial was evacuated and back flushed with Argon. Dry DMF (5 mL) and DIEA (0.99 mL, 5.7 mmol) were added via syringe and the mixture was deoxygenated by bubbling Argon gas through the stirred solution for 5 min. To the mixture were added CuI (5.4 mg, 0.028 mmol) and dichlorobis(triphenylphosphine)palladium(II) (40 mg, 0.057 mmol). The resulting mixture was stirred at rt for 1 h, and was poured into water (50 mL). The mixture was extracted with EtOAc (3×30 mL). The combined organic extracts were washed with water (20 mL) and brine (2×20 mL). The organic layer was concentrated, and the resulting residue was purified by flash column chromatography on silica gel (20-60% EtOAc/heptane) to give tert-butyl 4-(8-morpholino-2-(quinolin-2-ylethynyl)imidazo[1,2-b]pyridazin-3-yl)benzoate as a yellow solid.

1. customwas evacuated
2. customback flushed with Argon
3. customthe mixture was deoxygenated
4. customby bubbling Argon gas through the stirred solution for 5 min
5. extractionThe mixture was extracted with EtOAc (3×30 mL)
6. washThe combined organic extracts were washed with water (20 mL) and brine (2×20 mL)
7. concentrationThe organic layer was concentrated
8. customthe resulting residue was purified by flash column chromatography on silica gel (20-60% EtOAc/heptane)