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

HRID 375591Notes

Reaction equation

HRID 375591 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.CS(O[CH2:27][C:28]12[CH2:37][CH:32]3[CH2:33][CH:34]([CH2:36][CH:30]([CH2:31]3)[CH2:29]1)[CH2:35]2)(=O)=O>CN(C=O)C>[C:28]12([CH2:27][N:10]3[C:9]4[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=4[N:7]([C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=4)[C:6](=[O:21])[CH2:5][C:4]3=[O:3])[CH2:29][CH:30]3[CH2:36][CH:34]([CH2:33][CH:32]([CH2:31]3)[CH2:37]1)[CH2:35]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 28017761-Adamantylmethyl methanesulfonateHCID 10824683N-Desmethyl Dechloro Clobazam

Product 1

HCID 190434021-(1-Adamantyl)methyl-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepineYield 18.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride 80% dispersion in oil (0.07 g) was added portionwise to a solution of 2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine (0.5 g) in DMF (50 ml). The reaction mixture was stirred for 30 min, then a solution of 1-adamantylmethyl methanesulfonate (0.537 g) in DMF (3 ml) was added. The reaction mixture was stirred at 120° for 7 h and at 23° for 15 h, then concentrated. The residue was diluted with ethyl acetate (100 ml) washed with brine (2×30 ml) and water (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 (0.15 g). T.l.c. CH-EA (1:1), Rf =0.42.

Workup

  1. stirringThe reaction mixture was stirred at 120° for 7 h and at 23° for 15 h
  2. concentrationconcentrated
  3. additionThe residue was diluted with ethyl acetate (100 ml)
  4. washwashed with brine (2×30 ml) and water (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-3dc95db21735450aa7930dcefac8220d
Source dataset
uspto-grants-1996_01
Patent number
US05486514

Reaction notes

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