反应详情

A suspension of 10.02 g (32.00 mmol) of 1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-[1,4]diazepan-5-one (intermediate 1A]) and 6.27 g (32.00 mmol) of 3-bromo-N-methoxy-N-methyl-propionamide (intermediate 2C]) in 225 ml of THF was treated at 0° C. with 1.54 g (35.20 mmol) of NaH (55% in oil) in two portions. The suspension was stirred 4 h at RT, cooled and treated again at 0° C. with 1.54 g (35.20 mmol) of NaH (55% in oil) in two portions. The reaction was warmed up to RT over night, treated a third time at 0° C. with 1.54 g (35.20 mmol) of NaH (55% in oil) in two portions and stirred for 30 min at 50° C. After 20 h at RT, the reaction was 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 8.97 g (65%) of the title compound as an off-white foam. MS: 428.2 (MH+, 2Cl).

1. temperaturecooled
2. temperatureThe reaction was warmed up to RT over night
3. stirringstirred for 30 min at 50° C
4. waitAfter 20 h at RT
5. extractionextracted with EtOAc (3×)
6. washThe organic phases were washed with aqueous saturated NaHCO3, aqueous 10% NaCl
7. dry with materialdried over Na2SO4
8. customevaporated
9. custompurified by flash silica gel column (CH2Cl2/MeOH 99:1 to 97.5:2.5)