Acetic Acid → Ethyl 7-chloro-3-(3-chlorophenyl)-5-methyl-4-oxo-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-carboxylate

HRID 1280399Notes

Reaction equation

HRID 1280399 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([NH:9][NH2:10])[CH:6]=[CH:7][CH:8]=1.[OH-].[Na+].C(O)(=O)C.[Cl:17][C:18]1[CH:26]=[C:25]2[C:21]([C:22]([C:33](=O)[C:34]([O:36][CH2:37][CH3:38])=[O:35])=[C:23]([C:28](OCC)=[O:29])[N:24]2[CH3:27])=[CH:20][CH:19]=1>O>[Cl:17][C:18]1[CH:19]=[CH:20][C:21]2[C:22]3[C:33]([C:34]([O:36][CH2:37][CH3:38])=[O:35])=[N:10][N:9]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([Cl:2])[CH:4]=4)[C:28](=[O:29])[C:23]=3[N:24]([CH3:27])[C:25]=2[CH:26]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 75331m-Chlorophenylhydrazine hydrochlorideHCID 15461899Ethyl 6-chloro-2-(ethoxycarbonyl)-1-methyl-oxo-1h-indole-3-acetate

Product 1

HCID 18425198Ethyl 7-chloro-3-(3-chlorophenyl)-5-methyl-4-oxo-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-carboxylateYield 89.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

7.0 g (39.1 mmol) of 3-chlorophenylhydrazine hydrochloride are dissolved in 50 ml of water and 5 ml of a 35% sodium hydroxide solution. Extraction is carried out with diethyl ether. The organic phase is dried over sodium sulphate, filtered and concentrated under reduced pressure. An oil is obtained, to which are added 100 ml of acetic acid and 4.0 g (12.35 mmol) of ethyl 6-chloro-2-(ethoxycarbonyl)-1-methyl-α-oxo-1H-indole-3-acetate. The reaction mixture is stirred for 30 min at room temperature and then for 6 h at reflux. The mixture is cooled, 100 ml of water are added and an insoluble material is collected by filtration, washed with water and purified by chromatography on a silica column (eluant: dichloromethane/ethyl acetate: 98/2). 4.59 g (11 mmol) of compound are isolated in the form of a white solid.

Workup

  1. extractionExtraction
  2. dry with materialThe organic phase is dried over sodium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customAn oil is obtained, to which
  6. temperaturefor 6 h at reflux
  7. temperatureThe mixture is cooled
  8. filtrationan insoluble material is collected by filtration
  9. washwashed with water
  10. custompurified by chromatography on a silica column (eluant: dichloromethane/ethyl acetate: 98/2)

Sources & evidence

ORD record
ord-d4d04d5a9b1049639e9c9091e795b508
Source dataset
uspto-grants-2002_09
Patent number
US06451795B1

Reaction notes

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