Water → 7-Methyl-6-[(3-(1-methyl-4-piperazinyl) sulfonylpropyl)oxy]imidazo[1,2-b]pyridazine

HRID 2395968Notes

Reaction equation

HRID 2395968 reaction equation
[H-].[Na+].[CH3:3][N:4]1[CH2:9][CH2:8][N:7]([S:10]([CH2:13][CH2:14][CH2:15][OH:16])(=[O:12])=[O:11])[CH2:6][CH2:5]1.Cl[C:18]1[C:19]([CH3:27])=[CH:20][C:21]2[N:22]([CH:24]=[CH:25][N:26]=2)[N:23]=1.O>O1CCCC1.CN(C)C=O>[CH3:27][C:19]1[C:18]([O:16][CH2:15][CH2:14][CH2:13][S:10]([N:7]2[CH2:8][CH2:9][N:4]([CH3:3])[CH2:5][CH2:6]2)(=[O:12])=[O:11])=[N:23][N:22]2[CH:24]=[CH:25][N:26]=[C:21]2[CH:20]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 122483366-Chloro-7-methylimidazo[1,2-b]pyridazineHCID 152348893-(1-Methyl-4-piperazinylsulfonyl)-1-propanol

Product 1

HCID 538163707-Methyl-6-[(3-(1-methyl-4-piperazinyl) sulfonylpropyl)oxy]imidazo[1,2-b]pyridazineYield 50.5%

Reagents, catalysts & solvents 1

HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

In 20 ml of tetrahydrofuran-dimethylformamide (3:1) was suspended 110 mg of60% sodium hydride in oil followed by addition of 611 mg of 3-(1-methyl-4-piperazinylsulfonyl)-1-propanol and the mixture was stirred under nitrogen at room temperature for 30 minutes and at 50° C. for30 minutes. Then, 420 mg of 6-chloro-7-methylimidazo[1,2-b]pyridazine was added and the mixture was further stirred at 50° C. for 1 hour and at 70° C. for 1 hour. Following addition of 100 ml of iced water, the reaction mixture was extracted with ethylacetate (100 ml ). The extract was washed with 50 ml of saturated saline and dried over anhydrousmagnesium sulfate. The solvent was then distilled off under reduced pressure and the residue was subjected to silica gel column chromatography, elution being carried out with dichloromethanemethanol (50:3). The fraction containing the desired product were pooled and concentrated. The residue was recrystallized dichloromethane-isopropyl ether to obtain 447 mg of the title compound.

Workup

  1. stirringthe mixture was further stirred at 50° C. for 1 hour and at 70° C. for 1 hour
  2. extractionthe reaction mixture was extracted with ethylacetate (100 ml )
  3. washThe extract was washed with 50 ml of saturated saline
  4. dry with materialdried over anhydrousmagnesium sulfate
  5. distillationThe solvent was then distilled off under reduced pressure
  6. washthe residue was subjected to silica gel column chromatography, elution
  7. additionThe fraction containing the desired product
  8. concentrationconcentrated
  9. customThe residue was recrystallized dichloromethane-isopropyl ether

Sources & evidence

ORD record
ord-53c07997e02c4e6b864a79a7dd649c78
Source dataset
uspto-grants-1996_02
Patent number
US05491145

Reaction notes

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