反应详情

A mixture of 6-chloro-2-(2-chlorophenyl)-1,7-naphthyridin-4(1H)-one (29.2 mg, 100 μmol), cyclopropanecarboxamide (17.1 mg, 200 μmol), chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoeth yl)phenyl]palladium(II) (8.0 mg, 10 μmol), 2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl (5.4 mg, 10 μmol), and cesium carbonate (98.0 mg, 301 μmol) in 1,4-dioxane (5.0 mL) was heated to reflux for 4 hours. Further portions of cyclopropanecarboxamide (17.1 mg, 200 μmol), chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoeth yl)phenyl]palladium(II) (8.0 mg, 10 μmol) and 2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl (5.4 mg, 10 μmol) were added and the mixture heated to reflux for 16 hours. The cooled mixture was treated with water and brine and extracted with ethyl acetate, and the separated organic phase washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by reverse phase HPLC (gradient of acetonitrile in water with 0.1% formic acid) to afford the title compound as a white solid (2.1 mg, 6.2%). LCMS (Method E): RT=3.715 min, M+H+=340.0 & 342.0.

1. temperaturewas heated
2. temperatureto reflux for 4 hours
3. temperaturethe mixture heated
4. temperatureto reflux for 16 hours
5. extractionextracted with ethyl acetate
6. washthe separated organic phase washed with brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified by reverse phase HPLC (gradient of acetonitrile in water with 0.1% formic acid)