Sodium hydride → 2,3,4,5-Tetrahydro-N-(1-methylethyl)-N-(4-methylphenyl)-2,4-dioxo-5-phenyl-1H-1,5-benzodiazepine-1-acetamide

HRID 343142Notes

Reaction equation

HRID 343142 reaction equation
[C:1]1([N:7]2[C:13](=[O:14])[CH2:12][C:11](=[O:15])[NH:10][C:9]3[CH:16]=[CH:17][CH:18]=[CH:19][C:8]2=3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].Br[CH2:23][C:24]([N:26]([CH:34]([CH3:36])[CH3:35])[C:27]1[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=1)=[O:25]>CN(C=O)C>[O:15]=[C:11]1[N:10]([CH2:23][C:24]([N:26]([CH:34]([CH3:36])[CH3:35])[C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=2)=[O:25])[C:9]2[CH:16]=[CH:17][CH:18]=[CH:19][C:8]=2[N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:13](=[O:14])[CH2:12]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10824683N-Desmethyl Dechloro ClobazamHCID 537765772-Bromo-N-isopropyl-N-p-tolyl-acetamide

Product 1

HCID 676969062,3,4,5-Tetrahydro-N-(1-methylethyl)-N-(4-methylphenyl)-2,4-dioxo-5-phenyl-1H-1,5-benzodiazepine-1-acetamideYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 700 mg (2.78 mmol) 1-Phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-2,4-dione in 15 mL DMF is added 144 mg (3.61 mmol, 1.3 equiv) 60 wt % NaH at ambient temperature and stirred 0.5 h. To this solution is added 750 mg (2.78 mmol, 1.0 equiv) 2-Bromo-N-isopropyl-N-p-tolyl-acetamide, prepared as in Part B, in 1 mL DMF and stirred 18 h at ambient temperature. The solvent is removed in vacuo and the residue taken into 50 mL EtOAc and washed successively with H2O (30 mL), 1N HCl (30 mL), satd. NaHCO3 (30 mL), and brine (30 mL), dried (MgSO4), filtered and concentrated in vacuo to a yellow oil. The crude product is purified by flash chromatography on 27 g silica gel eluted successively with EtOAc/Hexanes (2:3, 500 mL), (1:1, 100 mL). Appropriate fractions were combined and concentrated in vacuo to give 554 mg (1.25 mmol) of 2-(2,4-Dioxo-5-phenyl-2,3,4,5,-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-p-tolyl-acetamide as a white foam: 1H NMR (CDCl3, 300 MHz) δ7.43-7.07 (m, 12H), 6.90 (d, 1H, J=8.3), 5.03 (m, 1H), 4.37 (d, 1H, J=16.6), 4.04 (d, 1H, J=16.6), 3.58 (d, 1H, J=11.9), 3.49 (d, 1H, J=11.7), 2.41 (s, 3H), 1.10 (d, 6H, J=6.6); TLC Rf =0.27 (EtOAc/Hexanes, 1:1).

Workup

  1. additionTo this solution is added
  2. customThe solvent is removed in vacuo
  3. washwashed successively with H2O (30 mL), 1N HCl (30 mL)
  4. dry with materialNaHCO3 (30 mL), and brine (30 mL), dried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to a yellow oil
  7. customThe crude product is purified by flash chromatography on 27 g silica gel
  8. washeluted successively with EtOAc/Hexanes (2:3, 500 mL), (1:1, 100 mL)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-94f51564feb842b386c93bdfc62046be
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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