Water → 7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

HRID 884998Notes

Reaction equation

HRID 884998 reaction equation
[Cl:1][C:2]1[CH:22]=[CH:21][C:5]2[NH:6][C:7](=[O:20])[CH:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[NH:9][C:10](=[O:11])[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:29][O:30][C:31]1[CH:38]=[CH:37][C:34]([CH2:35]Cl)=[CH:33][CH:32]=1.O>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:22]=[CH:21][C:5]2[N:6]([CH2:35][C:34]3[CH:37]=[CH:38][C:31]([O:30][CH3:29])=[CH:32][CH:33]=3)[C:7](=[O:20])[CH:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[NH:9][C:10](=[O:11])[C:4]=2[CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 699934-Methyloxybenzyl chlorideHCID 595943987-chloro-3-(2-chlorobenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione

Product 1

HCID 595943957-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dioneYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

7-Chloro-3-(2-chlorobenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione (0.8 g, 2.39 mmol), powdered potassium carbonate (0.495 g, 3.58 mmol) and 4-methoxybenzyl chloride (0.39 mL, 2.86 mmol) were suspended in N,N-dimethylformamide (20 mL) and stirred at ambient temperature overnight. The solution was poured into water (100 mL) and ethyl acetate (150 mL). The layers were separated and the organic layer was washed with water (2×100 mL) then brine, and dried with sodium sulfate, decanted and concentrated in the presence of silica gel. The product was purified by column chromatography eluting with a gradient of 0-50% ethyl acetate in hexanes to yield 7-chloro-3-(2-chlorobenzyl)-1-(4-methoxybenzyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione (0.65 g, 60%). 1H NMR (300 MHz, DMSO-d6) δ 3.06 (m, 1H), 3.30 (m, 2H), 3.66 (s, 3H), 4.13 (m, 1H), 4.82 (d, 1H), 5.34 (d, 1H), 6.76 (d, 2H, J=8.79 Hz), 6.96 (d, 2H, J=8.79 Hz), 7.21-29 (m, 2H), 7.36-45 (m, 2H), 7.54-7.61 (m, 3H), 8.97 (d, 1H, J=5.86 Hz); ESI m/z 455.1.

Workup

  1. customThe layers were separated
  2. washthe organic layer was washed with water (2×100 mL)
  3. dry with materialbrine, and dried with sodium sulfate
  4. customdecanted
  5. concentrationconcentrated in the presence of silica gel
  6. customThe product was purified by column chromatography
  7. washeluting with a gradient of 0-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-2a154dee3694424e85f1182e8ddd3ae7
Source dataset
uspto-grants-2012_08
Patent number
US08242109B2

Reaction notes

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