Acetohydrazide → 6-(o-fluorophenyl)-1,4,4-trimethyl-8-nitro-4H-s-triazolo[4,3-a][1,4]benzodiazepine

HRID 1758780Notes

Reaction equation

HRID 1758780 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=[CH:18][C:13]=2[NH:12][C:11](=O)[C:10]([CH3:24])([CH3:23])[N:9]=1.[H-].[Na+].[C:27]([NH:30][NH2:31])(=O)[CH3:28]>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:14]2[CH:15]=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=[CH:18][C:13]=2[N:12]2[C:27]([CH3:28])=[N:30][N:31]=[C:11]2[C:10]([CH3:24])([CH3:23])[N:9]=1

Participants

5

Reactant 3

HCID 14039AcetohydrazideHCID 24758Sodium hydrideHCID 205061515-(o-fluorophenyl)-1,3-dihydro-3,3-dimethyl-7-nitro-2H-1,4-benzodiazepin-2-one

Product 1

HCID 205085396-(o-fluorophenyl)-1,4,4-trimethyl-8-nitro-4H-s-triazolo[4,3-a][1,4]benzodiazepine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

55.25 g (0.16 mol) of 5-(o-fluorophenyl)-1,3-dihydro-3,3-dimethyl-7-nitro-2H-1,4-benzodiazepin-2-one, dissolved in 800 ml of tetrahydrofuran, are treated portionwise and while stirring at room temperature with 9.7 g of a 55 to 60 percent sodium hydride dispersion and the mixture is stirred at 50° C. for a further 60 minutes. 100 g (0.39 mol) of dimorpholinochlorophosphate are added to the cooled solution and the mixture is stirred at room temperature for 24 hours. After the addition of 50 g (0.67 mol) of acetic acid hydrazide, the mixture is stirred at room temperature for a further 45 hours and concentrated in vacuo. The residue is taken up in methylene chloride; the organic phase is washed with water and the solvent is removed. The residue is treated with 1.2 liters of n-butanol and heated to boiling under reflux. After distilling off 350 ml of solvent, the mixture remaining is heated at reflux for a further 1 hour and concentrated in vacuo. The residue is dissolved in 250 ml of hot ethanol. After cooling to -10° C., there is obtained crystalline 6-(o-fluorophenyl)-1,4,4-trimethyl-8-nitro-4H-s-triazolo[4,3-a][1,4]benzodiazepine of melting point 195° C.

Workup

  1. additionare treated portionwise
  2. stirringthe mixture is stirred at room temperature for 24 hours
  3. stirringthe mixture is stirred at room temperature for a further 45 hours
  4. concentrationconcentrated in vacuo
  5. washthe organic phase is washed with water
  6. customthe solvent is removed
  7. additionThe residue is treated with 1.2 liters of n-butanol
  8. temperatureheated
  9. temperatureunder reflux
  10. distillationAfter distilling off 350 ml of solvent
  11. temperaturethe mixture remaining is heated
  12. temperatureat reflux for a further 1 hour
  13. concentrationconcentrated in vacuo
  14. dissolutionThe residue is dissolved in 250 ml of hot ethanol
  15. temperatureAfter cooling to -10° C.

Sources & evidence

ORD record
ord-11107698dfa74ccaa31d65eeb2fcbe88
Source dataset
uspto-grants-1983_02
Patent number
US04374773

Reaction notes

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