Sodium hydride → 1-(3,3-Dimethylbut-1-yl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine

HRID 375589Notes

Reaction equation

HRID 375589 reaction equation
[H-].[Na+].[O:3]=[C:4]1[NH:10][C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[N:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:6](=[O:21])[CH2:5]1.[CH3:22][C:23]([CH3:32])([CH3:31])[CH2:24][CH2:25]CS([O-])(=O)=O>CN(C)C=O>[CH3:22][C:23]([CH3:32])([CH3:31])[CH2:24][CH2:25][N:10]1[C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[N:7]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:6](=[O:21])[CH2:5][C:4]1=[O:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10824683N-Desmethyl Dechloro ClobazamHCID 189929953,3-Dimethylbutylmethanesulphonate

Product 1

HCID 107356151-(3,3-Dimethylbut-1-yl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepineYield 42.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride 80% dispersion in oil (0.10 g) was added portionwise to a solution of 2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine (0.7 g) in dry dimethylformamide (60 ml). The reaction mixture was stirred for 30 min, then a solution of 3,3-dimethylbutylmethanesulphonate (0.575 g) in dry dimethylformamide (3 ml) was added. The reaction mixture was stirred at 90° for 50 min at 23° for 15 h, at 90° for 2h and at 140° for 45 min, then concentrated in vacuo. The residue was diluted with water (30 ml) and brine (20 ml) and extracted with ethyl acetate (150 ml); the organic layer was washed with water (2×50 ml) and brine (50 ml), dried and concentrated in vacuo. The crude product was purified by flash chromatography (eluting with CH-EA 1:1) to give the title compound as a white foam (0.4 g). T.l.c. CH-EA (1:1 ), Rf=0.39.

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe residue was diluted with water (30 ml) and brine (20 ml)
  3. extractionextracted with ethyl acetate (150 ml)
  4. washthe organic layer was washed with water (2×50 ml) and brine (50 ml)
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by flash chromatography (eluting with CH-EA 1:1)

Sources & evidence

ORD record
ord-871f203baeef496cb004cb3eee8ab650
Source dataset
uspto-grants-1996_01
Patent number
US05486514

Reaction notes

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