Phosphoric Acid → 6-phenyl-8-chloro-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-carboxaldehyde-diethylacetal

HRID 268029

Reaction equation

HRID 268029 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]3[C:19]([CH2:22][OH:23])=[N:20][N:21]=[C:10]3[CH2:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(N=C=N[CH:33]2[CH2:38]CCCC2)CCCCC1.P(=O)(O)(O)[OH:40].[C:44]1(C)C=CC(S(O)(=O)=O)=C[CH:45]=1>C(O)C.C(Cl)Cl.CS(C)=O>[CH2:44]([O:23][CH:22]([O:40][CH2:38][CH3:33])[C:19]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)[CH3:45]

Participants

8

Reactant 4

HCID 1004Phosphoric AcidHCID 6101p-Toluenesulfonic acidHCID 10868DicyclohexylcarbodiimideHCID 162244alpha-Hydroxyalprazolam

Product 1

HCID 215531066-phenyl-8-chloro-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-carboxaldehyde-diethylacetal

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of 300 mg of 6-phenyl-8-chloro-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-methanol, 0.57 g of dicyclohexyl-carbodiimide, 45 mg of phosphoric acid and 3 ml of abs. dimethylsulphoxide is stirred for 6 days at 25° and for a further 2 days at 70°-80°. Methylene chloride is then added, the organic phase washed with water and saturated sodium chloride solution, dried over magnesium sulphate and concentrated by evarporation. Crude 6-phenyl-8-chloro-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-carboxaldehyde is obtained, which is dissolved in 5 ml of ethanol. An addition is made to the obtained solution of 100 mg of p-toluenesulphonic acid, and the mixture refluxed for 10 hours. The solution is concentrated in vacuo. The residue is taken up in methylene chloride, the organic phase washed with 5% aqueous potassium carbonate solution and with saturated sodium chloride solution, dried over sodium sulphate, and concentrated by evaporation. The residue is recrystallised from ethyl acetate/ether/petroleum ether to obtain 6-phenyl-8-chloro-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-carboxaldehyde-diethylacetal, M.P. 133°-135°.

Workup

  1. washthe organic phase washed with water and saturated sodium chloride solution
  2. dry with materialdried over magnesium sulphate
  3. concentrationconcentrated by evarporation
  4. customCrude 6-phenyl-8-chloro-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-carboxaldehyde is obtained
  5. additionAn addition
  6. temperaturethe mixture refluxed for 10 hours
  7. concentrationThe solution is concentrated in vacuo
  8. washthe organic phase washed with 5% aqueous potassium carbonate solution and with saturated sodium chloride solution
  9. dry with materialdried over sodium sulphate
  10. concentrationconcentrated by evaporation
  11. customThe residue is recrystallised from ethyl acetate/ether/petroleum ether

Sources & evidence

ORD record
ord-1510bf09485843ca938db78524887de5
Source dataset
uspto-grants-1976_03
Patent number
US03946032

Linked notes

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