反应详情

342 mg of 3-bromo-5-(2,6-difluorophenyl)-2-(2-trimethylsilanylethoxymethyl)-7-iodo-2H-pyrazolo[4,3-c]isoquinoline are introduced into 13 ml of 1,4-dioxane. 74 mg of 4-pyrazoleboronic acid, 77 mg of Pd(PPh3)4 and 165 mg of sodium carbonate are added. The mixture is heated at reflux for 4 h 30 min. After cooling, the mixture is poured into water, extracted with AcOEt, washed with saturated NaCl solution, dried over MgSO4, filtered and concentrated under RP. The product is purified by flash chromatography on silica gel (15-40 μm), eluting with a DCM/methanol mixture (95/05 by vol.), to give 136 mg of 3-bromo-5-(2,6-difluorophenyl)-7-(1H-pyrazol-4-yl)-2-{[2-(trimethylsilyl)ethoxy]methyl}-2H-pyrazolo[4,3-c]isoquinoline (white foam), which is used as it is in the following step.

1. temperatureThe mixture is heated
2. temperatureat reflux for 4 h 30 min
3. temperatureAfter cooling
4. extractionextracted with AcOEt
5. washwashed with saturated NaCl solution
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under RP
9. customThe product is purified by flash chromatography on silica gel (15-40 μm)
10. washeluting with a DCM/methanol mixture (95/05 by vol.)