Acetic Acid → 6-phenyl-8-chloro-4H-s-triazolo[4,3-a] [1,4]benzodiazepine-1-carboxylic acid methyl ester

HRID 1605028Notes

Reaction equation

HRID 1605028 reaction equation
[C:1]1([C:7]2[C:13]3[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:12]=3[N:11]3C(C=O)=[N:20][N:21]=[C:10]3[CH2:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C-:24]#N.[Na+].[C:27]([OH:30])(=[O:29])[CH3:28]>CO.[O-2].[O-2].[Mn+4]>[CH3:24][O:29][C:27]([C:28]1[N:11]2[C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[N:8][CH2:9][C:10]2=[N:21][N:20]=1)=[O:30]

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 8929Sodium CyanideHCID 214860116-phenyl-8-chloro-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-carboxaldehyde

Product 1

HCID 123908826-phenyl-8-chloro-4H-s-triazolo[4,3-a] [1,4]benzodiazepine-1-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 178418406HCID 178418406, compoundCatalystHCID 887MethanolSolvent2×

Procedure

A mixture of 1.62 g (0.005 mole) of 6-phenyl-8-chloro-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-carboxaldehyde [cp. Example 1 a)], 20 ml of methanol, 1.225 g (0.025 mole) of sodium cyanide, 8.70 g (0.10 mole) of manganese dioxide and 0.40 g of glacial acetic acid is stirred for 16 hours at 25°. The reaction mixture is diluted with methanol, filtered through a layer of kieselguhr and the filtrate concentrated by evaporation. The residue is dissolved in methylene chloride, this solution washed with water and saturated sodium chloride solution, dried over magnesium sulphate and concentrated by evaporation. The oily residue is chromatographed on silica gel (Merck, 0.063 - 0.2 mm particle size) with ethyl acetate/methanol (9:1) as eluant. The fractions containing the desired product [Rf = 0.7 in the eluant system ethyl acetate/isopropanol (7:1)] are combined, concentrated by evaporation, and the residue crystallised from ethyl acetate to obtain 6-phenyl-8-chloro-4H-s-triazolo[4,3-a] [1,4]benzodiazepine-1-carboxylic acid methyl ester, M.P. 216°-217°.

Workup

  1. filtrationfiltered through a layer of kieselguhr
  2. concentrationthe filtrate concentrated by evaporation
  3. dissolutionThe residue is dissolved in methylene chloride
  4. washthis solution washed with water and saturated sodium chloride solution
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated by evaporation
  7. customThe oily residue is chromatographed on silica gel (Merck, 0.063 - 0.2 mm particle size) with ethyl acetate/methanol (9:1) as eluant
  8. additionThe fractions containing the desired product [Rf = 0.7 in the eluant system ethyl acetate/isopropanol (7:1)]
  9. concentrationconcentrated by evaporation
  10. customthe residue crystallised from ethyl acetate

Sources & evidence

ORD record
ord-41c9899b08084404bce5b8316b7b5d0b
Source dataset
uspto-grants-1976_04
Patent number
US03948931

Reaction notes

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