Dimethylformamide → HCID 89876203, compound

HRID 2169773Notes

Reaction equation

HRID 2169773 reaction equation
[Cl:1][C:2]1[N:3]([C:12]2[C:13](=[O:24])[N:14]([CH3:23])[N:15]=[C:16]([CH:20]([OH:22])[CH3:21])[C:17]=2[O:18][CH3:19])[C:4]2[C:9]([C:10]=1[Cl:11])=[CH:8][CH:7]=[CH:6][CH:5]=2.[H-].[Na+].[CH3:27]I.[CH3:29]N([CH:32]=[O:33])C>>[CH3:12][CH2:17][O:18][C:32]([CH3:27])=[O:33].[CH3:6][CH2:5][CH2:4][CH:9]([CH3:10])[CH3:8].[Cl:1][C:2]1[N:3]([C:12]2[C:13](=[O:24])[N:14]([CH3:23])[N:15]=[C:16]([CH:20]([O:22][CH3:29])[CH3:21])[C:17]=2[O:18][CH3:19])[C:4]2[C:9]([C:10]=1[Cl:11])=[CH:8][CH:7]=[CH:6][CH:5]=2

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 89876292HCID 89876292, compound

Product 2

HCID 21882781Isohexane ethyl acetateYield 0%HCID 89876203HCID 89876203, compoundYield 63%

Procedure

To a stirred solution of 4-(2,3-dichloroindol-1-yl)-6-(1-hydroxyethyl)-5-methoxy-2-methyl-pyridazin-3-one (98 mg, 0.27 mmol) in DMF (1 mL) at 0° C. is added sodium hydride (60% dispersion in mineral oil, 32 mg, 0.80 mmol). After stirring for 5 min, MeI (50 μL, 0.80 mmol) is added. After 30 min, the reaction is cautiously quenched with ammonium chloride solution (10 mL) and allowed to stand overnight. The following day, the reaction mixture is extracted with DCM (10 mL×3), then dried (MgSO4) and concentrated under reduced pressure. The residue is resubmitted to the reaction conditions with the same procedure and reagent/solvent quantities as above. After stirring for 30 min, it is warmed to RT and allowed to stir for a further 1.5 h. It is then cooled to 0° C. and then quenched cautiously with ammonium chloride solution (20 mL). Et2O is then added and the layers were separated. The organic layer is washed with water (20 mL×3), then dried (MgSO4) and concentrated under reduced pressure onto silica. Chromatography (0 to 30% EtOAc/isohexane) affords the desired product 4-(2,3-dichloroindol-1-yl)-5-methoxy-6-(1-methoxyethyl)-2-methyl-pyridazin-3-one (64 mg, 0.168 mmol, 63%) as a colourless oil.

Workup

  1. waitAfter 30 min
  2. customthe reaction is cautiously quenched with ammonium chloride solution (10 mL)
  3. waitto stand overnight
  4. extractionThe following day, the reaction mixture is extracted with DCM (10 mL×3)
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe residue is resubmitted to the reaction conditions with the same procedure and reagent/solvent quantities as above
  8. stirringAfter stirring for 30 min
  9. stirringto stir for a further 1.5 h
  10. temperatureIt is then cooled to 0° C.
  11. customquenched cautiously with ammonium chloride solution (20 mL)
  12. additionEt2O is then added
  13. customthe layers were separated
  14. washThe organic layer is washed with water (20 mL×3)
  15. dry with materialdried (MgSO4)
  16. concentrationconcentrated under reduced pressure onto silica

Sources & evidence

ORD record
ord-1765a792f040440f9979de60397f43e0
Source dataset
uspto-grants-2015_06
Patent number
US09049864B2

Reaction notes

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