反应详情

A suspension of 5.01 g (16.00 mmol) of 1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-[1,4]diazepan-5-one and 3.20 g (17.60 mmol) of 2-bromo-N-methoxy-N-methyl-acetamide (intermediate 1D) in 110 ml of THF was treated at 0° C. with 0.84 g (19.20 mmol) of NaH (55% in oil) in two portions. The reaction was warmed up to RT over night and stirred for 2.5 h at 75° C. The reaction was cooled and neutralized with cold aqueous 10% KHSO4 and extracted with EtOAc (3×). The organic phases were washed with aqueous saturated NaHCO3, aqueous 10% NaCl, dried over Na2SO4 evaporated and purified by flash silica gel column (CH2Cl2/MeOH 99:1 to 97.5:2.5) to yield 3.49 g (53%) of the light yellow crystalline title compound. MS: 414.1 (MH+, 2Cl).

1. temperatureThe reaction was cooled
2. extractionextracted with EtOAc (3×)
3. washThe organic phases were washed with aqueous saturated NaHCO3, aqueous 10% NaCl
4. dry with materialdried over Na2SO4
5. customevaporated
6. custompurified by flash silica gel column (CH2Cl2/MeOH 99:1 to 97.5:2.5)