Dimethylformamide → 2-{4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-ylmethyl}-acrylic acid ethyl ester
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([N:13]2[CH2:19][CH2:18][C:17](=[O:20])[NH:16][CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8].[H-].[Na+].CN([CH:26]=[O:27])C>>[CH2:11]([O:12][C:26](=[O:27])[C:2]([CH2:3][N:16]1[C:17](=[O:20])[CH2:18][CH2:19][N:13]([C:11](=[O:12])/[CH:10]=[CH:9]/[C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[CH2:14][CH2:15]1)=[CH2:7])[CH3:10]Participants
Conditions
- Temperature
- 18 °C
Procedure
A suspension of 2.50 g (7.98 mmol) of 1-[(E)-3-(3,4-dichloro-phenyl)-acryloyl]-[1,4]diazepan-5-one (intermediate 1A) and 1.15 ml (7.98 mmol) of ethyl 2-(bromomethylacrylate) in 80 ml of DMF was treated at −20° C. with 0.38 g (8.78 mmol) of NaH (55% in oil) and warmed up naturally to 18° C. (2.5 h). After cooling (0° C.) additionally 0.12 ml (0.80 mmol) of ethyl 2-(bromomethylacrylate) was added and after 30 min no starting material was left, based on TLC. The reaction was extracted with aqueous 10% KHSO4/ether (3×), the organic phases were washed with a aqueous 10% NaCl solution, dried (Na2SO4) and evaporated to give 3.51 g (quantitative, 90% purity) of the crude title compound as light yellow viscous oil, which was used directly in the next step. MS: 425.1 (MH+, 2Cl).
Workup
- additionwas added and after 30 min no starting material
- waitwas left
- extractionThe reaction was extracted with aqueous 10% KHSO4/ether (3×)
- washthe organic phases were washed with a aqueous 10% NaCl solution
- dry with materialdried (Na2SO4)
- customevaporated
Sources & evidence
- ORD record
- ord-5cefa1a4ce934999875495726625e69f
- Source dataset
- uspto-grants-2009_12
- Patent number
- US07632829B2
Reaction notes
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