Sodium hydride → 2-{4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-N-methoxy-N-methyl-acetamide

HRID 1867351

Reaction equation

HRID 1867351 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].Br[CH2:22][C:23]([N:25]([O:27][CH3:28])[CH3:26])=[O:24].[H-].[Na+].OS([O-])(=O)=O.[K+]>C1COCC1>[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])[N:16]([CH2:22][C:23]([N:25]([O:27][CH3:28])[CH3:26])=[O:24])[CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 516920Potassium bisulfateHCID 108669612-Bromo-N-methoxy-N-methylacetamide2×HCID 620449211-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-[1,4]diazepan-5-one

Product 1

HCID 866158622-{4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-N-methoxy-N-methyl-acetamideYield 53%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-8b95c50dfb50425e8b7c46783a52c771
Source dataset
uspto-grants-2009_12
Patent number
US07632829B2

Linked notes

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