反应 #1951086

反应方程式

ammonium chloride

2-(4-fluoro-2-methyl-phenylamino)-7-(1-hydroxy-allyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one

triethylamine

acetic anhydride

→

acetic acid 1-[2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinolin-7-yl]-allyl ester

收率 55.0%

溶剂

THF

反应条件

后处理

1. 1
   其他To a 25 mL round-bottom flask equipped with a magnetic stir bar
2. 2
   其他all reaction components
3. 3
   workup.DISSOLUTIONwere fully dissolved
4. 4
   萃取the solution was extracted with ethyl acetate (2×20 mL)
5. 5
   其他The organic fractions were collected
6. 6
   洗涤washed with brine (1×20 mL)
7. 7
   干燥dried over sodium sulfate
8. 8
   浓缩concentrated in vacuo
9. 9
   其他The crude product was further purified by silica gel chromatography
10. 10
    洗涤eluting with 2% methanol

实验过程

To a 25 mL round-bottom flask equipped with a magnetic stir bar was added 2-(4-fluoro-2-methyl-phenylamino)-7-(1-hydroxy-allyl)-1,6-dimethyl-1,8-dihydro-imidazo[4,5-h]isoquinolin-9-one (0.65 g, 1.7 mmol), THF (5 mL), triethylamine (0.52 g, 5.1 mmol) and acetic anhydride (0.22 g, 2.2 mmol). To the stirred suspension was then added DMAP (0.002 g, 0.02 mmol). After 1 hour, all reaction components were fully dissolved and the reaction was complete as determined by TLC analysis. To the reaction mixture was added saturated aqueous ammonium chloride (20 mL) and the solution was extracted with ethyl acetate (2×20 mL). The organic fractions were collected, washed with brine (1×20 mL), dried over sodium sulfate, and concentrated in vacuo. The crude product was further purified by silica gel chromatography, eluting with 2% methanol:DCM to provide acetic acid 1-[2-(4-fluoro-2-methyl-phenylamino)-1,6-dimethyl-9-oxo-8,9-dihydro-1H-imidazo[4,5-h]isoquinolin-7-yl]-allyl ester (0.404 g, 55%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6+TFA) δ ppm 11.35 (br s, 1H), 10.55 (br s, 1H), 7.74 (d, 1H, J=9.0 Hz), 7.70 (d, 1H, J=8.6 Hz), 7.56 (dd, 1H, J1=5.5 Hz, J2=8.6 Hz), 7.37-7.34 (m, 3H), 7.25 (td, 1H, J1=2.7 Hz, J2=8.2 Hz), 6.34 (app d, 1H, J=6.3 Hz), 6.17 (ddd, 1H, J1=6.3 Hz, J2=10.2 Hz, J3=16.8 Hz), 5.41 (app d, 1H, J=17.2 Hz), 5.33 (app d, 1H, J=10.2 Hz), 4.18 (s, 3H), 2.32 (s, 3H), 2.12 (s, 3H); ESMS (m/z): found, 435.

来源