反应详情

温度

0 °C

To a solution of 1-(4-chlorophenyl)-3,3-dimethyl-1H-benzo[b][1,4]diazepine-2,4(3H,5H)-dione (100 mg, 0.32 mmol) in THF (10 mL) was added a solution of t-BuOK (35.8 mg, 0.32 mmol) dropwise at −78° C. over 10 min. The solution was slowly warmed up to 0° C. in 30 min and recooled to −78° C. for the addition of dimethyl phosphorochloridate (55 mg, 0.38 mmol). The mixture was warmed up to 0° C. over 30 min and stirred for 1 hour at room temperature. The solution was cooled to −78° C. and a solution of acetohydrazide (28 mg, 0.38 mmol) in THF (5 mL) was added. The mixture was heated to reflux for 3 hours. The crude solution was diluted with water (20 mL) and extracted with ethyl acetate (20 mL*3). The combined organic layers were dried over Na2SO4, concentrated in vacuo and the residue was purified by column chromatography (silica-gel, DCM: methanol=20:1) to give 6-(4-chlorophenyl)-1,4,4-trimethyl-4H-benzo[b][1,2,4]triazolo[4,3-d][1,4]diazepin-5(6H)-one as a white solid (51 mg, yield 44%) LRMS (M+H+) m/z: calcd 352.11. found 352.

1. temperatureThe mixture was warmed up to 0° C. over 30 min
2. temperatureThe solution was cooled to −78° C.
3. temperatureThe mixture was heated
4. temperatureto reflux for 3 hours
5. extractionextracted with ethyl acetate (20 mL*3)
6. dry with materialThe combined organic layers were dried over Na2SO4
7. concentrationconcentrated in vacuo
8. customthe residue was purified by column chromatography (silica-gel, DCM: methanol=20:1)