反应详情

温度

0 °C

A suspension of N-(2-ethoxy-3-isopropylbenzyl)-3-[4-(4-methoxybenzyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl]-N-methylacrylamide (0.200 g, 0.369 mmol) in dichloroethane (8.0 mL) was cooled in an ice bath and treated with 1-chloroethyl chloroformate (0.044 mL, 0.40 mmol). After stirring at 0° C. under N2 for 30 min and then at room temperature for 30 min, the mixture was heated to reflux for 2 h. The mixture was allowed to cool and then concentrated to dryness. Purification by flash column chromatography (silica gel, CH2Cl2 to CH2Cl2/MeOH, 100 to 99.5:0.5) gave a white solid (0.128 g, 0.241 mmol). The solid was dissolved in methanol (4 mL) and heated to reflux for 6.5 h. The mixture was allowed to cool and the resulting solid was isolated by filtration, washed with MeOH and Et2O and dried to give the title compound (1.28 g, 46%) as a white powder and as a mixture of amide rotamers: 1H NMR (300 MHz, DMSO-d6) δ 11.08-11.06 (m, 1H), 9.96 (br s, 2H), 8.77-8.71 (m, 1H), 8.32-8.23 (m, 1H), 7.63-7.55 (m, 1H), 7.40-7.32 (m, 1H), 7.26-7.21 (m, 1H), 7.13-7.04 (m, 1H), 6.91-6.84 (m, 1H), 4.83-4.67 (m, 2H), 4.27-4.22 (m, 2H), 3.88-3.78 (m, 4H), 3.29-2.25 (m, 1H), 3.13-2.89 (m, 3H), 1.40-1.35 (m, 3H), 1.19-1.17 (m, 6H); MS (ESI) m/e 423 (M+H)+.

1. temperaturewas cooled in an ice bath
2. waitat room temperature for 30 min
3. temperaturethe mixture was heated
4. temperatureto reflux for 2 h
5. temperatureto cool
6. concentrationconcentrated to dryness
7. customPurification by flash column chromatography (silica gel, CH2Cl2 to CH2Cl2/MeOH, 100 to 99.5:0.5)