反应详情

A mixture of 2-chlorofuro[2,3-c]pyridin-7-amine (4.0 g, 23.8 mmol) and 5-isoquinoline boronic acid (4.33 g, 25.0 mmol) in 1,4-dioxane (150 mL) and water (50 mL) was sparged with nitrogen for 15 min and then treated with Pd(PPh3)2Cl2 (250 mg). After sparging with nitrogen for another 5 min, K2CO3 (2.2 g, 59.5 mmol) was added and the mixture heated at reflux overnight. The 1,4-dioxane was removed in vacuo and DCM was added. The phases were separated and the organic phase was washed with water, then brine. The solution was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (2% MeOH:DCM) to provide the 5.6 g (90%) of the title compound. 1H NMR (300 MHz, CD3OD): δ 6.99 (d, J=5.4 Hz, 1H), 7.27 (s, 1H), 7.73 (d, J=5.4 Hz, 1H); 7.81 (t, J=8.1 Hz, 1H), 8.22 (d, J=8.1 Hz, 1H), 8.29 (dd, J=7.4 Hz, J=1.0 Hz, 1H), 8.44 (d, J=5.4 Hz, 1H), 8.55 (d, J=6.0 Hz, 1H); 9.32 (s, 1 H).

1. customwas sparged with nitrogen for 15 min
2. additiontreated with Pd(PPh3)2Cl2 (250 mg)
3. customAfter sparging with nitrogen for another 5 min
4. temperaturethe mixture heated
5. temperatureat reflux overnight
6. customThe 1,4-dioxane was removed in vacuo and DCM
7. additionwas added
8. customThe phases were separated
9. washthe organic phase was washed with water
10. dry with materialThe solution was dried over anhydrous Na2SO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. customThe residue was purified by flash chromatography (2% MeOH:DCM)