Acetohydrazide → Triazolam

HRID 649264Notes

Reaction equation

HRID 649264 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=O)[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[C:6]=2[CH:20]=1.[H-].[Na+].[H-].[H][H].O1CCN(P(Cl)(N2CCOCC2)=O)CC1.[C:41]([NH:44][NH2:45])(=O)[CH3:42]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:41]([CH3:42])=[N:44][N:45]=[C:10]3[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[Cl:19])[C:6]=2[CH:20]=1

Participants

8

Reactant 6

HCID 14039AcetohydrazideHCID 17925DelorazepamHCID 24758Sodium hydrideHCID 166653HydrideHCID 12506606Bis(morpholino)phosphinyl chlorideHCID 178418361HCID 178418361, compound

Product 1

HCID 5556Triazolam

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 610 mg. (2 mmoles) of 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one in 10 ml. of dry tetrahydrofuran at room temperature was added 115 mg. of a 50% dispersion of sodium hydride in oil (2.4 mmoles of hydride). The mixture was warmed gently on the steam bath for approximately 1 hour until hydrogen evolution stopped. Dimorpholinophosphinic chloride (764 mg., 3.0 mmoles) was added and the resulting mixture was stirred at room temperature for 2 hours. To this mixture was then added a solution of 296 mg. (4 mmoles) of acethydrazide in 5 ml. of dry tetrahydrofuran and stirring was continued for 15 minutes at room temperature. Solvents were evaporated and the residue was dissolved in 20 ml. of butanol and heated to reflux for 2 hours. Butanol was evaporated. The residue was partitioned between methylene chloride and water. The methylene chloride layer was dried and evaporated. Crystallization of the residue from isopropanol-ether-petroleum ether yielded, in two crops, final product having a m.p. of 225°-227°.

Workup

  1. additionTo this mixture was then added a solution of 296 mg
  2. waitwas continued for 15 minutes at room temperature
  3. customSolvents were evaporated
  4. dissolutionthe residue was dissolved in 20 ml
  5. temperatureof butanol and heated
  6. temperatureto reflux for 2 hours
  7. customButanol was evaporated
  8. customThe residue was partitioned between methylene chloride and water
  9. dry with materialThe methylene chloride layer was dried
  10. customevaporated
  11. customCrystallization of the residue from isopropanol-ether-petroleum ether

Sources & evidence

ORD record
ord-81ea9a22fdd84a6dbd5c76e1402448c5
Source dataset
uspto-grants-1988_04
Patent number
US04739049

Reaction notes

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