Dichloromethane → 2-(1-(4-amino-3-(2-(hydroxymethyl)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-(3-fluorophenyl)-4H-chromen-4-one

Participants

Reaction Conditions

Reaction Steps

To a solution of Example 57c (0.300 g, 0.568 mmoles) in DMF (3 ml), ethanol (1.5 ml) and water (1.5 ml), 2-Hydroxymethylphenylboronic acid (0.173 g, 1.137 mmoles) and sodium carbonate (0.301 g, 2.844 mmoles) were added and the system is degassed for 30 min. Tetrakistriphenylphosphine Palladium (0.129 g, 0.112 mmoles) was added under nitrogen atmosphere and heated to 80° C. After 12 h, the reaction mixture was celite filtered, concentrated and extracted with ethyl acetate. The organic layer was dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by column chromatography with methanol:dichloromethane to afford the title compound as off-white solid (0.090 g, 31% yield). MP: 185-189° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 8.09 (s, 1H), 8.04 (dd, J=7.9, 1.4 Hz, 1H), 7.84 (m, 1H), 7.66-7.35 (m, 10H), 7.17 (dt, J=10.8, 1.4 Hz, 1H), 7.04 (m, 1H), 6.01 (q, J=6.7 Hz, 1H), 5.13 (t, J=5.7 Hz, 1H), 4.54 (m, 2H), 1.87 (d, J=7.1 Hz, 3H). Mass: 508.16 (M++1).

Provenance & Evidence