反应详情

A mixture of 5-(6-cyclopropylpyrazin-2-yl)-3-iodo-1H-indazole (192 mg, 0.53 mmol), 3,4-dihydro-2 h-pyran (96 μL, 1.06 mmol) and p-toluenesulfonic acid monohydrate (20 mg, 0.106 mmol) in THF (3 mL) was heated at reflux overnight (9 h). After cooling to RT, the mixture was concentrated to about 1 mL. The mixture was diluted with EtOAc and saturated NaHCO3 (aq.) and the layers were separated. The aqueous layer was extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude was purified by silica gel chromatography, eluting with a gradient of 0-30% EtOAc in hexanes, to provide 5-(6-cyclopropylpyrazin-2-yl)-3-iodo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (140 mg, 0.31 mmol, 59% yield) as a pale yellow foam. MS (ESI, pos. ion) m/z: 447.0 (M+1).

1. temperaturewas heated
2. temperatureat reflux overnight (9 h)
3. concentrationthe mixture was concentrated to about 1 mL
4. additionThe mixture was diluted with EtOAc and saturated NaHCO3 (aq.)
5. customthe layers were separated
6. extractionThe aqueous layer was extracted with EtOAc (3×)
7. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude was purified by silica gel chromatography
11. washeluting with a gradient of 0-30% EtOAc in hexanes