Reaction Steps
To a solution of 6-[(6-chloropyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one (Example 1, 0.080 g, 0.19 mmol) and pyrazole (0.052 g, 0.15 mmol) in 2 mL of DMSO under an atmosphere of nitrogen was added potassium carbonate (0.57 mL, 1 N aqueous, 0.57 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (21.6 mg, 0.152 mmol), and copper(I) iodide (0.014 g, 0.076 mmol). The mixture was heated at 120° C. for 20 h, cooled to rt, and additional trans-N,N′-dimethylcyclohexane-1,2-diamine (21.6 mg, 0.152 mmol) and copper(I) iodide (0.014 g, 0.076 mmol) were added. The reaction was heated at 150° C. for 24 h, cooled to rt, and diluted with ethyl acetate and water. The aqueous layer was extracted 3× with ethyl acetate, and the combined organic fractions were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane, to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 453.51 for [M+H]+: 1H NMR (400 MHz, CD3OD) δ 8.93 (d, J=7.3 Hz, 1H), 8.46 (s, 1H), 8.30 (s, 1H), 8.26 (s, 1H), 7.90 (s, 1H), 7.86 (d, J=9.2 Hz, 1H), 7.79 (d, J=8.5 Hz, 1H), 7.66-7.57 (m, 2H), 7.50 (d, J=8.5 Hz, 1H), 6.39 (s, 1H), 6.30 (s, 1H), 4.86-4.84 (m, 1H), 4.36 (s, 2H), 4.23-4.13 (m, 2H), 4.12-4.04 (m, 1H), 3.56-3.50 (m, 1H), 3.34-3.32 (m, 1H), 2.24-2.19 (m, 1H), 2.00-1.97 (m, 1H).
