反应详情

温度

100 °C

A mixture of 2-benzyl-4-bromoisoquinolin-1(2H)-one (0.500 g, 1.59 mmol) and 3,4,5-trimethoxyaniline (0.349 g, 1.91 mmol) in dry toluene (30 mL) was degassed under nitrogen. Pd2(dba)3 (0.218 g, 0.24 mmol) and BINAP (0.297 g, 0.48 mmol) were added and the mixture was degassed again. Sodium tert-butoxide (0.306 g, 3.18 mmol) was then added and the reaction was stirred at 100° C. for 17 h under nitrogen. After that time, the reaction mixture was cooled to rt, diluted with water (20 mL) and extracted with ethyl acetate (3×20 mL). The organic phase was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The product was purified by flash column chromatography (silica gel, 25:75 hexanes/ethyl acetate to 50:50 hexanes/ethyl acetate) followed by trituration with methanol to give 2-benzyl-4-((3,4,5-trimethoxyphenyl)amino)isoquinolin-1(2H)-one (0.183 g, 28%) as a light brown solid: mp 162-164° C.; 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J=8.2 Hz, 1H), 7.61-7.68 (m, 2H), 7.54 (ddd, J=8.2, 5.6, 2.7 Hz, 1H), 7.27-7.35 (m, 5H), 7.17 (s, 1H), 5.85 (s, 2H), 5.23 (s, 2H), 5.10 (s, 1H), 3.75 (s, 3H), 3.65 (s, 6H); ESI MS m/z 417 [M+H]+.

1. customwas degassed under nitrogen
2. customthe mixture was degassed again
3. temperatureAfter that time, the reaction mixture was cooled to rt
4. extractionextracted with ethyl acetate (3×20 mL)
5. washThe organic phase was washed with brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated under reduced pressure
8. customThe product was purified by flash column chromatography (silica gel, 25:75 hexanes/ethyl acetate to 50:50 hexanes/ethyl acetate)