Sodium hydride → N-Cyclopropyl-2-(2,4-dioxo-5-phenyl-2,3,4,5,tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-phenyl-acetamide

HRID 343144Notes

Reaction equation

HRID 343144 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:33]1[CH2:35][CH2:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:25]>CN(C=O)C>[CH:33]1([N:26]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:24](=[O:25])[CH2:23][N:10]2[C:11](=[O:15])[CH2:12][C:13](=[O:14])[N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:8]3[CH:19]=[CH:18][CH:17]=[CH:16][C:9]2=3)[CH2:35][CH2:34]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 107060812-bromo-N-cyclopropyl-N-phenyl-acetamideHCID 10824683N-Desmethyl Dechloro Clobazam

Product 1

HCID 10788516N-Cyclopropyl-2-(2,4-dioxo-5-phenyl-2,3,4,5,tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-phenyl-acetamideYield 67.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a stirred solution of 500 mg (1.98 mmol) 1-Phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-2,4-dione in 15 mL DMF is added 103 mg (2.58 mmol, 1.3 equiv) 60 wt % NaH at ambient temperature and stirred 0.5 h. To this solution is added 504 mg (1.98 mmol, 1.0 equiv) 2-Bromo-N-cyclopropyl-N-phenyl-acetamide, prepared as in Part A, 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, 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 brown oil. The crude product is purified by flash chromatography on 15 g silica gel eluted with EtOAc/Hexanes (1:1, 450 mL). Appropriate fractions were combined and concentrated in vacuo to give 572 mg (1.34 mmol) of N-Cyclopropyl-2-(2,4-dioxo-5-phenyl-2,3,4,5,tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-phenyl-acetamide as a white foam: 1H NMR (CDCl3, 300 MHz) δ7.50-7.07 (m, 13H), 6.92 (d, 1H, J=7.3), 3.60 (d, 1H, J=11.9), 3.51 (d, 1H, J=12.0), 3.30 (m, 1H), 0.86 (m, 2H), 0.60 (m, 2H); TLC Rf =0.35 (EtOAc/Hexanes, 2:1).

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 brown oil
  7. customThe crude product is purified by flash chromatography on 15 g silica gel
  8. washeluted with EtOAc/Hexanes (1:1, 450 mL)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-65726c883abe4173b0747dd583a57d62
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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