反应详情

温度

160 °C

To a mixture of 3-bromo-N-butylimidazo[1,2-b]pyridazin-6-amine (100 mg, 0.37 mmol), (4-formylphenyl)boronic acid (139 mg, 0.93 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (13.5 mg, 0.02 mmol) and potassium phosphate (236 mg, 1.11 mmol) was added 3:1 dimethoxyethane/water (2 mL). The resulting mixture was heated at 160° C. (microwave) for 6 min. After the reaction was cooled down and separated into two layers, the dark upper layer was then filtered and diluted with a mixture of 1:1:1 methanol/water/acetonitrile, and then filtered again. The filtration was finally purified by preparative HPLC (neutral) to afford 4-(6-(butylamino)imidazo[1,2-b]pyridazin-3-yl)benzaldehyde (78 mg, 72% yield) as a yellow solid: 1H NMR (METHANOL-d4) δ: 10.01 (s, 1H), 8.47 (d, J=8.6 Hz, 2H), 7.98-8.03 (m, 2H), 7.97 (s, 1H), 7.66 (d, J=9.6 Hz, 1H), 6.77 (d, J=9.6 Hz, 1H), 3.42 (t, J=7.1 Hz, 2H), 1.74 (t, J=7.2 Hz, 2H), 1.52 (d, J=7.8 Hz, 2H), 1.03 (t, J=7.5 Hz, 4H); LRMS (ESI) m/e 295.2 [(M+H)+, calcd for C17H19N4O 295.2].

1. temperatureAfter the reaction was cooled down
2. customseparated into two layers
3. filtrationthe dark upper layer was then filtered
4. additiondiluted with a mixture of 1:1:1 methanol/water/acetonitrile
5. filtrationfiltered again
6. filtrationThe filtration
7. customwas finally purified by preparative HPLC (neutral)