Sodium hydride → Adinazolam

HRID 903029Notes

Reaction equation

HRID 903029 reaction equation
[CH3:1][N:2]([CH3:4])O.[H-].[Na+].[Cl:7][C:8]1[CH:9]=[CH:10][C:11]2[N:17]3[C:18]([CH2:21]Cl)=[N:19][N:20]=[C:16]3[CH2:15][N:14]=[C:13]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:12]=2[CH:29]=1>CN(C)C=O>[Cl:7][C:8]1[CH:9]=[CH:10][C:11]2[N:17]3[C:18]([CH2:21][N:2]([CH3:4])[CH3:1])=[N:19][N:20]=[C:16]3[CH2:15][N:14]=[C:13]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:12]=2[CH:29]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27970DimethylhydroxylamineHCID 126123458-chloro-1-(chloromethyl)-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine

Product 1

HCID 37632Adinazolam

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of N,N-dimethylhydroxylamine (3.67 g, 0.06 mole) in dry dimethylformamide (50 ml) is cooled in an ice bath, under nitrogen, and treated with a 57% mineral oil suspension of sodium hydride (0.84 g, 0.02 mole). The mixture is kept at ambient temperature for 1 hour (a precipitate formed) and then cooled in an ice bath and treated with 8-chloro-1-(chloromethyl)-6-phenyl-4H-s-triazolo[4,3-a][1,4]-benzodiazepine (6.86 g, 0.02 mole). The mixture is kept at ambient temperature for 2 hours and concentrated in vacuo. Last traces of dimethylformamide are removed from the residue by the successive addition and distillation with xylene, toluene, and benzene. The resulting material is chromatographed on silica gel (250 g) with methanol. The product thus obtained is crystallized from methanol-ethyl acetate (following activated charcoal treatment) to give 8-chloro-1-[(dimethylamino)methyl]-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine, N1 -oxide, hydrate in three crops: 3.377 g of melting point 160.5°-162.5° C.; 1.145 g of melting point 160°-162° C.; and 0.785 g of melting point 160°-162° C. The analytical sample had a melting point of 157.5°-158.5° C. with decomposition.

Workup

  1. custom(a precipitate formed) and
  2. temperaturethen cooled in an ice bath
  3. waitThe mixture is kept at ambient temperature for 2 hours
  4. concentrationconcentrated in vacuo
  5. customLast traces of dimethylformamide are removed from the residue by the successive addition and distillation with xylene, toluene, and benzene
  6. customThe resulting material is chromatographed on silica gel (250 g) with methanol
  7. customThe product thus obtained
  8. customis crystallized from methanol-ethyl acetate (following activated charcoal treatment)

Sources & evidence

ORD record
ord-e5fe3668e0404bc1bdac7329317071ac
Source dataset
uspto-grants-1980_10
Patent number
US04226772

Reaction notes

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