反应详情

To a suspension of 3,4-diamino-1-methyl-1H-quinolin-2-one (0.60 g, 1.59 mmol) in CH2Cl2 (10 mL) were added Et3N (0.177 g, 1.74 mmol) and 4-chlorocarbonyl-piperidine-1-carboxylic acid benzyl ester (0.45 g, 1.60 mmol) at 0° C. The reaction mixture was stirred at room temperature for 1.5 h, and then excess acid chloride was quenched by addition of MeOH. The mixture was concentrated in vacuo, and the amide intermediate was taken up in 5 mL of HOAc and heated at reflux for 7 h. After cooling to room temperature, the solvent was evaporated under reduced pressure. The cyclized product was purified by flash chromatography, to give 4-(5-methyl-4-oxo-4,5-dihydro-3H-imidazo[4,5-c]quinolin-2-yl)-piperidine-1-carboxylic acid benzyl ester (0.12 g, 18% yield). 1H-NMR (DMSO): δ 8.08 (m, 1H), 7.60 (m, 1H), 7.43 (m, 1H), 7.32 (m, 6H), 5.02 (s, 2H), 3.91 (m, 2H), 3.34 (s, 3H), 2.81 (m, 3H), 1.78 (m, 2H), 1.39 (m, 2H). MS: calculated for C24H24N4O3+H 417.2; found: 417.4.

1. customexcess acid chloride was quenched by addition of MeOH
2. concentrationThe mixture was concentrated in vacuo
3. temperatureheated
4. temperatureat reflux for 7 h
5. temperatureAfter cooling to room temperature
6. customthe solvent was evaporated under reduced pressure
7. customThe cyclized product was purified by flash chromatography