反应详情

To a solution of 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]pyrido[3,4-h]quinazolin-4(3H)-one (Example 1, 0.050 g, 0.12 mmol) in 1 mL of dioxane under an atmosphere of nitrogen was added 2-(tributylstannyl)-pyrazine (0.175 g, 0.475 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.014 g, 0.012 mmol). The mixture was irradiated in a microwave reactor at 160° C. for 1 h, cooled to rt, and diluted with ethyl acetate. The organic solution was washed with saturated aqueous sodium bicarbonate and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 464.9 for [M+H]: 1H NMR (400 MHz, CD3OD) δ 9.84 (s, 1H), 9.51 (s, 1H), 9.32 (d, J=6.2 Hz, 1H), 8.84 (d, J=6.2 Hz), 8.75-8.64 (m, 4H), 8.41 (d, J=8.2 Hz, 1H), 8.34 (s, 1H), 7.96-7.94 (m, 1H), 4.86 (s, 2H), 4.16 (br s, 1H), 2.19 (br s, 1H), 2.03 (br s, 1H), 1.96-1.86 (m, 3H), 1.56-1.42 (m, 4H).

1. customThe mixture was irradiated in a microwave reactor at 160° C. for 1 h
2. washThe organic solution was washed with saturated aqueous sodium bicarbonate and brine
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified via preparative reverse phase HPLC