Dimethylformamide → HCID 86686761, compound

HRID 1403130Notes

Reaction equation

HRID 1403130 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][CH3:10])[N:3]=1.[F:11][CH:12]([F:25])[C:13]1[NH:17][C:16]2[CH:18]=[CH:19][CH:20]=[C:21]([O:22][CH2:23][CH3:24])[C:15]=2[N:14]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[Cl:8][C:6]1[N:5]=[C:4]([S:9][CH3:10])[N:3]=[C:2]([N:17]2[C:16]3[CH:18]=[CH:19][CH:20]=[C:21]([O:22][CH2:23][CH3:24])[C:15]=3[N:14]=[C:13]2[CH:12]([F:11])[F:25])[CH:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 805314,6-Dichloro-2-(methylthio)pyrimidineHCID 56595292HCID 56595292, compound

Product 1

HCID 86686761HCID 86686761, compoundYield 34.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of 4,6-dichloro-2-(methylsulfanyl)pyrimidine (700 mg), 2-(difluoromethyl)-4-ethoxy-1H-benzimidazole (761 mg), potassium carbonate (744 mg), and N,N-dimethylformamide (7 mL) was stirred at room temperature overnight. To the mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The desiccant was removed by filtration and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=100:0-80:20) to obtain 1-[6-chloro-2-(methylsulfanyl)pyrimidin-4-yl]-2-(difluoromethyl)-4-ethoxy-1H-benzimidazole (464 mg) (Preparation Example 86-1) and 1,1′-[2-(methylsulfanyl)pyrimidine-4,6-diyl]bis[2-(difluoromethyl)-4-ethoxy-1H-benzimidazole]. 1,1′-[2-(Methylsulfanyl)pyrimidine-4,6-diyl]bis[2-(difluoromethyl)-4-ethoxy-1H-benzimidazole] was suspended in ethyl acetate and warmed. After leaving to be cooled, the insoluble matter was collected by filtration to obtain 1,1′-[2-(methylsulfanyl)pyrimidine-4,6-diyl]bis[2-(difluoromethyl)-4-ethoxy-1H-benzimidazole] (275 mg) (Preparation Example 86-2).

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe desiccant was removed by filtration
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (chloroform:methanol=100:0-80:20)

Sources & evidence

ORD record
ord-6a38d895a5a440978d0197bd7fcbdc35
Source dataset
uspto-grants-2014_12
Patent number
US08912180B2

Reaction notes

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