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

HRID 1867353

Reaction equation

HRID 1867353 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][CH2:23][C:24]([N:26]([O:28][CH3:29])[CH3:27])=[O:25].[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][CH2:23][C:24]([N:26]([O:28][CH3:29])[CH3:27])=[O:25])[CH2:15][CH2:14]2)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 4

HCID 24758Sodium hydride3×HCID 516920Potassium bisulfateHCID 112063733-bromo-N-methoxy-N-methylpropanamideHCID 620449211-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-[1,4]diazepan-5-one

Product 1

HCID 866158643-[4-[(E)-3-(3,4-Dichloro-phenyl)-acryloyl]-7-oxo-[1,4]diazepan-1-yl}-N-methoxy-N-methyl-propionamideYield 65.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-82e4e1b5855f4b44bd5e0af415ea3d45
Source dataset
uspto-grants-2009_12
Patent number
US07632829B2

Linked notes

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