Chloride → 3-[(1S,2S)-2-Hydroxycyclohexyl]-6-[(6-methylpyridin-3-yl)methyl]pyrido[3,4-h]quinazolin-4(3H)-one

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Reaction Conditions

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, 0.030 g, 0.071 mmol) in 1 mL of THF under an atmosphere of nitrogen was added methylzine chloride (2 M in THF, 0.107 mL, 0.214 mmol) and tetrakis(triphenylphosphine)palladium(0) (3.0 mg, 0.0026 mmol). The reaction was heated at 90° C. for 3 h, cooled to rt, and diluted with saturated aqueous sodium bicarbonate and ethyl acetate. The layers were partitioned, and the organic solution was washed with brine, 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 proton NMR spectra consistent with theory and a mass ion (ES+) of 401.0 for [M+H]+: 1H NMR (400 MHz, CDCl3) δ 9.11 (s, 1H), 8.43 (s, 2H), 8.19 (s, 2H), 7.86 (s, 1H), 7.34-7.32 (m, 1H), 7.04 (s, 1H), 5.30 (s, 2H), 4.53-4.49 (m, 2H), 4.22 (br s, 1H), 2.49 (s, 3H), 2.32-2.29 (m, 1H), 2.04-2.01 (m, 1H), 1.91-1.89 (m, 1H), 1.58-1.46 (m, 3H).

Provenance & Evidence