Cesium carbonate → N-[(1S,2S)-2-Hydroxycyclohexyl]-1-methoxy-4-{[6-(1-methyl-1H-pyrazol-4-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) in 3 mL of THF under an atmosphere of nitrogen was added aqueous cesium carbonate (1 M, 0.24 mL, 0.24 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.037 g, 0.18 mmol), and bis(tri-tert-butylphosphine)palladium(0) (4.0 mg, 0.0078 mmol). The reaction was heated at 100° C. for 16 hours, cooled to room temperature, 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 470.9 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 8.84 (s, 1H), 8.59 (s, 1H), 8.26-8.23 (m, 1H), 8.12 (d, J=7.1 Hz, 1H), 8.07-7.89 (m, 3H), 7.85-7.82 (m, 1H), 7.70-7.61 (m, 3H), 4.52 (s, 2H), 4.04 (s, 3H), 4.00 (s, 3H), 3.98 (br s, 1H), 3.57-3.51 (m, 1H), 2.16-2.13 (m, 2H), 1.79 (br s, 2H), 1.50-1.21 (m, 4H).

Provenance & Evidence