Pyrazole → 1-Hydroxy-N-[(1S,2S)-2-hydroxycyclohexyl]-4-{[6-(1H-pyrazol-1-yl)pyridine-3-yl]methyl}-2-naphthamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-[(6-chloropyridin-3-yl)methyl]-N-[(1S,2S)-2-hydroxycyclohexyl]-1-methoxy-2-naphthamide (Example 3, 0.050 g, 0.12 mmol) and pyrazole (8.0 mg, 0.12 mmol) in 2 mL of DMSO under an atmosphere of nitrogen was added aqueous cesium carbonate (1 N, 0.23 mL, 1 N aqueous, 0.23 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (2.2 mg, 0.015 mmol), and copper(I) iodide (1.4 g, 0.0076 mmol). The mixture was heated at 120° C. for 20 hours, cooled to room temperature, and additional trans-N,N′-dimethylcyclohexane-1,2-diamine (2.16 mg, 0.015 mmol) and copper(I) iodide (1.4 mg, 0.0076 mmol) were added. The reaction was heated at 140° C. for 24 hours, cooled to room temperature, filtered, and 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 442.9 for [M+H]+: 1H NMR (400 MHz, CD3OD) δ 8.50-8.47 (m, 2H), 8.33 (s, 1H), 7.84-7.81 (m, 1H), 7.76-7.74 (m, 2H), 7.60-7.51 (m, 2H), 7.24-7.20 (m, 2H), 6.48 (br s, 1H), 6.37 (d, J=6.2 Hz, 1H), 4.36 (s, 2H), 3.95-3.92 (m, 1H), 3.58-3.51 (m, 1H), 2.16-2.13 (m, 2H), 1.81-1.78 (m, 2H), 1.46-1.25 (m, 4H).

Provenance & Evidence