Toluene → 7-Chloro-3-(3-chlorophenyl)-N,N,5-trimethyl-4-oxo-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-carboxamide

HRID 1280400Notes

Reaction equation

HRID 1280400 reaction equation
Cl.[CH3:2][NH:3][CH3:4].C1(C)C=CC=CC=1.C[Al](C)C.[Cl:16][C:17]1[CH:18]=[CH:19][C:20]2[C:21]3[C:30]([C:31](OCC)=[O:32])=[N:29][N:28]([C:36]4[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=4)[C:27](=[O:43])[C:22]=3[N:23]([CH3:26])[C:24]=2[CH:25]=1>ClCCl.O>[Cl:16][C:17]1[CH:18]=[CH:19][C:20]2[C:21]3[C:30]([C:31]([N:3]([CH3:4])[CH3:2])=[O:32])=[N:29][N:28]([C:36]4[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=4)[C:27](=[O:43])[C:22]=3[N:23]([CH3:26])[C:24]=2[CH:25]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10473Dimethylamine, hydrochlorideHCID 16682925TrimethylaluminumHCID 18425198Ethyl 7-chloro-3-(3-chlorophenyl)-5-methyl-4-oxo-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-carboxylate

Product 1

HCID 99316427-Chloro-3-(3-chlorophenyl)-N,N,5-trimethyl-4-oxo-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-carboxamideYield 52.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

0.815 g (10 mmol) of dimethylamine hydrochloride is introduced into 100 ml of toluene under argon, the solution is cooled to 0° C. and then 5 ml (10 mmol) of a trimethylaluminium solution (2M in toluene) are added in small portions. After stirring for 2 h at room temperature, 0.8 g (1.92 mmol) of ethyl 7-chloro-3-(3-chlorophenyl)-5-methyl-4-oxo-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-carboxylate is added and the mixture is heated at reflux for 5 h. The solution is cooled to approximately 0° C. and the metal complex is slowly hydrolysed with water. 100 ml of dichloromethane are added and the solution is filtered. The precipitate is rinsed with dichloromethane, and 100 ml of water and 10 ml of a 1 M aqueous hydrochloric acid solution are added to the filtrate. The organic phase is separated by settling, washed with water, dried over sodium sulphate and concentrated under reduced pressure. The residue is purified by chromatography on a silica column (eluant: dichloromethane/ethyl acetate: 80/20). After recrystallizing from ethyl acetate, 0.43 g (1.0 mmol) of compound is isolated in the form of a white solid.

Workup

  1. temperaturethe mixture is heated
  2. temperatureat reflux for 5 h
  3. temperatureThe solution is cooled to approximately 0° C.
  4. filtrationthe solution is filtered
  5. washThe precipitate is rinsed with dichloromethane, and 100 ml of water and 10 ml of a 1 M aqueous hydrochloric acid solution
  6. additionare added to the filtrate
  7. customThe organic phase is separated
  8. washwashed with water
  9. dry with materialdried over sodium sulphate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue is purified by chromatography on a silica column (eluant: dichloromethane/ethyl acetate: 80/20)
  12. customAfter recrystallizing from ethyl acetate

Sources & evidence

ORD record
ord-54bb8ba2f3c94073b1e0a0fbd1f2035c
Source dataset
uspto-grants-2002_09
Patent number
US06451795B1

Reaction notes

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