Dimethylformamide → 5-({3-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-4-oxo-3,4-dihydrobenzo[h]quinazolin-6-yl}methyl)pyridine-2-carbonitrile

Participants

Reaction Conditions

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 (0.100 g, 0.237 mmol) in 1 mL of DMF under an atmosphere of nitrogen was added zinc cyanide (Example 1, 0.084 g, 0.71 mmol) and tetrakis(triphenylphosphine)palladium(0) (13.7 mg, 0.012 mmol). The mixture was heated to 100° C. for 8 h, then at 140° C. for another 15 h. The reaction was cooled to rt, diluted with ethyl acetate, washed 3× with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via preparative reverse phase HPLC to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 413.1603 for [M+H]+ [Calc'd for C24H21N4O3, [M+H]+=413.1608]: 1H NMR (400 MHz, CDCl3) δ 8.96-8.94 (m, 1H), 8.56 (s, 1H), 8.29 (s, 1H), 7.98 (s, 1H), 7.78-7.75 (m, 1H), 7.64-7.59 (m, 2H), 7.50 (s, 2H), 4.72-4.69 (m, 1H), 4.49 (s, 2H), 4.11-4.05 (m, 2H), 4.04-3.98 (m, 1H), 3.50-3.47 (m, 1H), 3.29-3.20 (m, 2H), 2.17-2.13 (m, 1H), 2.00-1.95 (m, 1H).

Provenance & Evidence