反应详情

A mixture of methyl [7-bromo-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate (160 mg, 0.329 mmol) and Zn(CN)2 (38.6 mg, 0.329 mmol) in N,N-Dimethylformamide (DMF) (3289 μl) was degassed with N2 for 5 min, treated with Pd(Ph3P)4 (38.0 mg, 0.033 mmol), and irradiated in microwave at 120° C. for 30 min. The mixture was diluted with water, extracted with EtOAc, washed with water, brine, dried with Na2SO4, filtered, and concentrated. the residue was purified by column chromatography (SiO2, 0-60% EtOAc/Hexane) to afford methyl [7-cyano-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate (116.8 mg, 0.270 mmol, 82% yield) as colorless oil that slowly became a white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.85-8.76 (m, 1 H), 7.65 (ddd, J=1.9, 6.1, 8.3 Hz, 1 H), 7.30-7.24 (m, 1 H), 7.23-7.09 (m, 2 H), 7.07-6.96 (m, 1 H), 5.22 (s, 1 H), 3.80 (s, 1.5 H), 3.78 (s, 1.5 H), 3.70 (s, 1.5 H), 3.69 (s, 1.5 ; H), 2.37 (s, 3 H), 2.32 (s, 3 H), 1.02 (s, 4.5 H), 1.01 (s, 4.5 H); LCMS (m/z) ES+=433 (M+1).

1. customwas degassed with N2 for 5 min
2. customirradiated in microwave at 120° C. for 30 min
3. extractionextracted with EtOAc
4. washwashed with water, brine
5. dry with materialdried with Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customthe residue was purified by column chromatography (SiO2, 0-60% EtOAc/Hexane)