Methanol → 7-Chloro-5-methyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetonitrile

HRID 1384837Notes

Reaction equation

HRID 1384837 reaction equation
CC(C)(C)[O-].[K+].CC1C=CC(S([CH2:17][N+:18]#[C-])(=O)=O)=CC=1.[Cl:20][C:21]1[CH:22]=[CH:23][C:24]2[C:25]3[C:34]([CH:35]=O)=[N:33][N:32]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:31](=[O:43])[C:26]=3[N:27]([CH3:30])[C:28]=2[CH:29]=1.CO>COCCOC>[Cl:20][C:21]1[CH:22]=[CH:23][C:24]2[C:25]3[C:34]([CH2:35][C:17]#[N:18])=[N:33][N:32]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:31](=[O:43])[C:26]=3[N:27]([CH3:30])[C:28]=2[CH:29]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 161915Tosylmethyl isocyanideHCID 154619027-Chloro-5-methyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-carboxaldehydeHCID 23665647Potassium tert-butoxide

Product 1

HCID 154619037-Chloro-5-methyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetonitrileYield 62.8%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
-60 °C

Procedure

1.27 g (10.96 mmol) of potassium 1,1-dimethylethoxide are added, in small portions, to a solution of 2.14 g (10.96 mmol) of (4-methylbenzenesulphonyl)methyl isocyanide in 50 ml of 1,2-dimethoxyethane, the reaction mixture is stirred for 30 min at −60° C., 2.88 g (8.53 mmol) of 7-chloro-5-methyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-carboxaldehyde are added and the reaction mixture is stirred for 3 hours 30 min at −60° C. 9 ml of methanol are added and the reaction mixture is further stirred for 30 min at room temperature and for 1 hour at reflux. The mixture is cooled and concentrated under reduced pressure, water, 5 ml of acetic acid and 200 ml of dichloromethane are added to the residue, the organic phase is separated by settling and the aqueous phase is extracted with dichloromethane. The organic phases are combined, washed with water, dried over sodium sulphate, filtered and concentrated under reduced pressure and the residue is purified by chromatography on a column of silica gel. 1.87 g (5.36 mmol) of compound are isolated in the form of a white solid which is used as is in the following stage.

Workup

  1. stirringthe reaction mixture is stirred for 3 hours 30 min at −60° C
  2. stirringthe reaction mixture is further stirred for 30 min at room temperature and for 1 hour
  3. temperatureat reflux
  4. temperatureThe mixture is cooled
  5. concentrationconcentrated under reduced pressure, water, 5 ml of acetic acid and 200 ml of dichloromethane
  6. additionare added to the residue
  7. customthe organic phase is separated
  8. extractionthe aqueous phase is extracted with dichloromethane
  9. washwashed with water
  10. dry with materialdried over sodium sulphate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customthe residue is purified by chromatography on a column of silica gel

Sources & evidence

ORD record
ord-9ae4698835a342bf92c0eb159990b9b2
Source dataset
uspto-grants-2001_07
Patent number
US06262045B1

Reaction notes

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