反应详情

A mixture of 2-chloro-4-iodofuro[2,3-c]pyridin-7-amine (7.7 g, 26.2 mmol) and tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylate (10.52 g, 27.7 mmol) in 1,2-dimethoxyethane (300 mL) and water (100 mL) was sparged with N2 for 15 min, then treated with K2CO3 and Pd(PPh3)4. After sparging again with N2 for 5 min, the mixture was heated at reflux 4-6 h. The 1,2-dimethoxyethane was removed in vacuo, water was added and the mixture extracted with DCM. The combined DCM extracts were dried, filtered and concentrated in vacuo. The residue was purified by flash chromatography using triethylamine-coated silica (2% MeOH:DCM) to afford 10 g (80%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 1.44-1.55 (m, 9H) 1.90-2.12 (m, 2H) 2.21 (d, J=10.61 Hz, 2H) 2.84-3.03 (m, 2H) 4.22-4.44 (m, 3H) 5.26 (br s, 2H) 6.77 (s, 1H) 7.65 (s, 1H) 7.73-7.79 (m, 1H) 7.92 (s, 1H).

1. customwas sparged with N2 for 15 min
2. additiontreated with K2CO3 and Pd(PPh3)4
3. customAfter sparging again with N2 for 5 min
4. temperaturethe mixture was heated
5. temperatureat reflux 4-6 h
6. customThe 1,2-dimethoxyethane was removed in vacuo, water
7. additionwas added
8. extractionthe mixture extracted with DCM
9. dry with materialThe combined DCM extracts were dried
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe residue was purified by flash chromatography