Reaction Steps
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, 0.070 g, 0.17 mmol) in 2 mL of THF under an atmosphere of nitrogen was added cesium carbonate (0.33 mL, 1 N aqueous, 0.33 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.052 g, 0.19 mmol), and bis(tri-tert-butylphosphine)palladium(0) (10 mol %). The reaction was heated at 85° C. for 20 h, and additional 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.040 g, 0.19 mmol), and bis(tri-tert-butylphosphine)palladium(0) (7.0 mg, 0.014 mmol) were added. After 5 h, the reaction was cooled to rt, diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate and brine. The solution was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-10% methanol in dichloromethane, to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 466.9 for [M+H]+: 1H NMR (400 MHz, CD3OD) δ 9.64 (s, 1H), 9.03 (d, J=6.0 Hz, 1H), 8.80 (d, J=5.4 Hz, 1H), 8.65 (s, 1H), 8.59 (s, 1H), 8.35 (s, 1H), 8.19 (s, 2H), 8.13 (s, 1H), 8.00 (d, J=8.4 Hz, 1H), 4.18 (br s, 1H), 3.99 (s, 2H), 3.31 (s, 3H), 2.20 (br s, 1H), 2.00 (br s, 2H), 1.87 (br s, 2H), 1.52-1.39 (m, 4H).
