Water → 1-[4-(4-Chlorobenzoyl)benzyl]-2,3-dichloro-5-methyl-1H-pyrrolo[2,3-d]pyridazin-4(5H)-one

HRID 1291268Notes

Reaction equation

HRID 1291268 reaction equation
[Cl:1][C:2]1[NH:12][C:5]2[CH:6]=[N:7][N:8]([CH3:11])[C:9](=[O:10])[C:4]=2[C:3]=1[Cl:13].[H-].[Na+].[Cl:16][C:17]1[CH:32]=[CH:31][C:20]([C:21]([C:23]2[CH:30]=[CH:29][C:26]([CH2:27]Br)=[CH:25][CH:24]=2)=[O:22])=[CH:19][CH:18]=1.O>CN(C=O)C>[Cl:16][C:17]1[CH:18]=[CH:19][C:20]([C:21]([C:23]2[CH:30]=[CH:29][C:26]([CH2:27][N:12]3[C:5]4[CH:6]=[N:7][N:8]([CH3:11])[C:9](=[O:10])[C:4]=4[C:3]([Cl:13])=[C:2]3[Cl:1])=[CH:25][CH:24]=2)=[O:22])=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 98396514-(4-Chlorobenzoyl)benzyl bromideHCID 1356675802,3-Dichloro-5-methyl-1H-pyrrolo[2,3-d]pyridazin-4(5H)-one

Product 1

HCID 189189391-[4-(4-Chlorobenzoyl)benzyl]-2,3-dichloro-5-methyl-1H-pyrrolo[2,3-d]pyridazin-4(5H)-oneYield 42.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of 2,3-dichloro-5-methyl-1H-pyrrolo[2,3-d]pyridazin-4(5H)-one (404 mg) in DMF (70 ml) was dripped into a suspension of 60% sodium hydride-oil (96 mg) in DMF (10 ml) on an ice-water bath. After 3 hours of stirring at room temperature, a solution of 4-(4-chlorobenzoyl)benzyl bromide (681 mg) in DMF (15 ml) was added and the mixture was further stirred at room temperature for 18 hours. The reaction was stopped by adding water and the reaction mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was then purified by silica gel column chromatography (developer; n-hexane: ethyl acetate=2:1→1:1) to provide the title compound as white powder (351 mg, yield 39%). 1H-NMR (DMSO-d6) δ: 3.68(3H,s), 5.73(2H,s), 7.30(2H,d,J=8.6Hz), 7.61(2H,d,J=8.6Hz), 7.72(2H,d,J=8.6Hz), 7.73(2H,d,J=8.6Hz), 8.71(1H,s).

Workup

  1. stirringthe mixture was further stirred at room temperature for 18 hours
  2. extractionthe reaction mixture was extracted with ethyl acetate
  3. dry with materialThe extract was dried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled off under reduced pressure
  5. customThe residue was then purified by silica gel column chromatography (developer; n-hexane: ethyl acetate=2:1→1:1)

Sources & evidence

ORD record
ord-f9a871829bc64c8e97ca51d2c5a0ca0a
Source dataset
uspto-grants-1998_05
Patent number
US05753664

Reaction notes

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