反应详情

温度

120 °C

To a nitrogen de-gassed solution of 7-ethynylisoindolin-1-one (161) (0.074 g, 0.47 mmol) and tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperazine-1-carboxylate (I3) (0.180 g, 0.393 mmol), in dry DMF (7 mL) were added triethylamine (0.219 mL, 1.57 mmol) followed by triphenylphosphine (0.015 g, 0.059 mmol), trans-dichlorobis(triphenylphosphine)palladium(II) (0.028 g, 0.039 mmol) and CuI (0.011 g, 0.059 mmol). The reaction mixture was heated under microwave irradiation at 120° C. for 20 minutes and then concentrated to dryness in vacuo and purified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C., then 0-5% methanol in EtOAc) to give the title compound (I62) (0.151 g, 66% yield) as an orange gum; 1H NMR (400 MHz, d6-DMSO) δ 10.32 (s, 1H), 8.77 (s, 1H), 8.72 (s, 1H), 7.75-7.67 (m, 2H), 7.67-7.64 (m, 1H), 7.60-7.56 (m, 2H).), 6.95 (d, J=9.1 Hz, 2H), 4.40 (s, 2H), 3.51-3.42 (m, 4H), 3.11-3.00 (m, 4H), 1.42 (s, 9H). LCMS Method C: rt 6.23 min, m/z 579.2 [M+H]+.

1. concentrationconcentrated to dryness in vacuo
2. custompurified by silica gel chromatography (Biotage Isolera, 40 g Si cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.