Acetohydrazide → 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1]benzazepine

HRID 358047Notes

Reaction equation

HRID 358047 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=O)[CH2:9][CH:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1.[H-].[Na+].N1(P(Cl)(N2CCOCC2)=O)CCOCC1.[C:37]([NH:40][NH2:41])(=O)[CH3:38]>O1CCCC1.C(O)CCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:37]([CH3:38])=[N:40][N:41]=[C:10]3[CH2:9][CH:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1

Participants

7

Reactant 4

HCID 14039AcetohydrazideHCID 24758Sodium hydrideHCID 12506606Bis(morpholino)phosphinyl chlorideHCID 204499557-chloro-5-phenyl-1,3-dihydro-2H-1-benzazepin-2-one

Product 1

HCID 204500088-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1]benzazepine

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1.075 g of 7-chloro-5-phenyl-1,3-dihydro-2H-1-benzazepin-2-one in 20 ml of dry tetrahydrofuran is treated with 0.23 g of sodium hydride (50% dispersion in mineral oil) and stirred at 60° for 1 hour. The mixture is then cooled to room temperature, treated with 1.53 g of bis-(4-morpholinyl)phosphinic acid chloride and stirred at this temperature for a further 2 hours. A solution of 0.593 g of acetic acid hydrazide in 50 ml of n-butanol is subsequently added thereto, the mixture is heated to boiling under reflux for 1 hour and then evaporated in vacuo. The residue is partitioned between water and methylene chloride. The methylene chloride solution is evaporated and the residue is chromatographed on 100 g of aluminium oxide (activity grade III). Various impurities and starting material are eluted successively with benzene and ethyl acetate/hexane (1:1). After elution with chloroform/ethanol (96:4) and recrystallization of the crude product from ethyl acetate/benzene/n-hexane, there is obtained 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1]benzazepine of melting point 235°.

Workup

  1. stirringstirred at this temperature for a further 2 hours
  2. temperaturethe mixture is heated
  3. temperatureunder reflux for 1 hour
  4. customevaporated in vacuo
  5. customThe residue is partitioned between water and methylene chloride
  6. customThe methylene chloride solution is evaporated
  7. customthe residue is chromatographed on 100 g of aluminium oxide (activity grade III)
  8. washare eluted successively with benzene and ethyl acetate/hexane (1:1)
  9. washAfter elution
  10. customwith chloroform/ethanol (96:4) and recrystallization of the crude product from ethyl acetate/benzene/n-hexane

Sources & evidence

ORD record
ord-8b99ebfee3fb439eb82f3b4e13c852b6
Source dataset
uspto-grants-1984_08
Patent number
US04464300

Reaction notes

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