p-Toluenesulfonic acid → HCID 15563865, compound

HRID 1863511Notes

Reaction equation

HRID 1863511 reaction equation
[NH2:1][C:2]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[Cl:12])=O.[CH3:18][CH:19]([CH2:34][C:35](=O)[CH3:36])[C:20](=O)[CH2:21][N:22]1C(=O)C2=CC=CC=C2C1=O.C1(C)C=CC(S(O)(=O)=O)=CC=1.CN(C)C=O>C1C=CC=CC=1>[Cl:17][C:14]1[CH:15]=[CH:16][C:2]2[N:1]3[C:35]([CH3:36])=[CH:34][C:19]([CH3:18])=[C:20]3[CH2:21][N:22]=[C:4]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[Cl:12])[C:3]=2[CH:13]=1

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 6228DimethylformamideHCID 180692-Amino-2',5-dichlorobenzophenoneHCID 155638332-(3-Methyl-2,5-dioxohexyl)-1H-isoindole-1,3(2H)-dione

Product 1

HCID 15563865HCID 15563865, compoundYield 54.3%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

2-Amino-2',5-dichlorobenzophenone (200 mg, 0.752 millimole) and 3-methyl-1-phthalimidohexane-2,5-dione (225 mg, 0.823 millimole) were dissolved in 10 ml of benzene, and 20 mg of p-toluenesulfonic acid was added. The mixture was heated under reflux for 4 hours, and 2 ml of N,N-dimethylformamide was added. The benzene was evaporated under reduced pressure, and 8 ml of ethanol and 0.3 ml of hydrazine hydrate were added. The mixture was heated under reflux for 30 minutes. The ethanol was evaporated under reduced pressure, and 25 ml of benzene was added. The mixture was heated under reflux for 5 minutes. After cooling, the solid was separated by filtration. The filtrate was washed with water and an aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the concentrate was chromatographed on silica gel. The column was first eluted with benzene to recover unchanged 2-amino-2',5-dichlorobenzophenone, and then with benzene-ethyl acetate (49:1) to afford 145 mg of 8-chloro-6-(2-chlorophenyl)-1,3-dimethyl-4H-pyrrolo[1,2-a][1,4]benzodiazepine as yellow crystals in a yield of 54%. The product showed the same spectral data as those of the compound obtained in Example 32.

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 4 hours
  3. customThe benzene was evaporated under reduced pressure, and 8 ml of ethanol and 0.3 ml of hydrazine hydrate
  4. additionwere added
  5. temperatureThe mixture was heated
  6. temperatureunder reflux for 30 minutes
  7. customThe ethanol was evaporated under reduced pressure, and 25 ml of benzene
  8. additionwas added
  9. temperatureThe mixture was heated
  10. temperatureunder reflux for 5 minutes
  11. temperatureAfter cooling
  12. customthe solid was separated by filtration
  13. washThe filtrate was washed with water
  14. dry with materialan aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate
  15. customThe solvent was evaporated under reduced pressure
  16. customthe concentrate was chromatographed on silica gel
  17. washThe column was first eluted with benzene
  18. customto recover unchanged 2-amino-2',5-dichlorobenzophenone

Sources & evidence

ORD record
ord-f902117450fe4bf1a15b4116280a6ca7
Source dataset
uspto-grants-1979_09
Patent number
US04169150

Reaction notes

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