Sodium hydride → 4-(2-(benzyloxy)ethyl)-1-methyl-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

HRID 2044115Notes

Reaction equation

HRID 2044115 reaction equation
[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)=[CH:12][C:7]=2[C:6](=[O:24])[NH:5][CH2:4][C:3]1=[O:25].[H-].[Na+].[H][H].Br[CH2:31][CH2:32][O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>CN(C=O)C>[CH2:34]([O:33][CH2:32][CH2:31][N:5]1[C:6](=[O:24])[C:7]2[CH:12]=[C:11]([C:13]3[CH:14]=[CH:15][C:16]([O:19][C:20]([F:23])([F:21])[F:22])=[CH:17][CH:18]=3)[CH:10]=[CH:9][C:8]=2[N:2]([CH3:1])[C:3](=[O:25])[CH2:4]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 73833Benzene, ((2-bromoethoxy)methyl)-HCID 711831331-Methyl-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dioneHCID 178418361HCID 178418361, compound

Product 1

HCID 711832234-(2-(benzyloxy)ethyl)-1-methyl-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dioneYield 61.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-Methyl-7-(4-(trifluoromethoxy)phenyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione (50.0 mg, 0.143 mmol) and NaH (17 mg, 0.428 mmol, 3.0 equiv.) were placed in a 2-5 mL Smith process vial under a nitrogen atmosphere. To the vial was added DMF (5 mL) to observe hydrogen extlusion. And then ((2-bromoethoxy)methyl)benzene (45 μL, 0.285 mmol, d=0.135, 2 equiv.) was added at room temperature. After stirring for 50 min, the reaction was quenched with AcOH. Resulting mixture was directly injected to a preparative HPLC to give the desired product (4-(2-(benzyloxy)ethyl)-1-methyl-7-(4-(trifluoromethoxy)-phenyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione, 42.7 mg) as a light yellow film.

Workup

  1. customthe reaction was quenched with AcOH
  2. customResulting mixture

Sources & evidence

ORD record
ord-4f8fdab2926c4103b32de44020ac3c89
Source dataset
uspto-grants-2013_11
Patent number
US08586732B2

Reaction notes

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