Pyrazole → 3-[(1S,2S)-2-Hydroxycyclohexyl]-6-{[6-(1H-pyrazol-1-yl)pyridine-3-yl]methyl}pyrido[2,3-h]quinazolin-4(3H)-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 6-[(6-chloropyridin-3-yl)methyl]-3-[(1S,2S)-2-hydroxycyclohexyl]pyrido[2,3-h]quinazolin-4(3H)-one (0.063 g, 0.15 mmol) and pyrazole (0.015 g, 0.22 mmol) in 1 mL of DMSO and 0.2 mL of water under an atmosphere of nitrogen was added potassium phosphate (0.095 g, 0.45 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (21.3 mg, 0.150 mmol), and copper(I) iodide (8.6 mg, 0.045 mmol). The mixture was heated at 120° C. for 30 h, cooled to rt, and diluted with dichloromethane. The organic solution was washed 3× with water, 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 453.2034 for [M+H]+ [Calc'd for C26H25N6O2, [M+H]+=453.2034]: 1H NMR (400 MHz, CDCl3) δ 9.24-9.22 (m, 1H), 9.10-9.08 (m, 1H), 8.50 (s, 1H), 8.46 (s, 1H), 8.27-8.26 (m, 2H), 7.85-7.77 (m, 2H), 7.68 (s, 1H), 7.62-7.59 (m, 1H), 6.42 (s, 1H), 4.68 (s, 2H), 4.66-4.64 (m, 1H), 4.02 (br s, 1H), 2.27-2.25 (m, 1H), 2.06-2.03 (m, 1H), 1.90 (br s, 3H), 1.56-1.44 (m, 3H).

Provenance & Evidence