Benzimidazole → 2-Ethylthio-4-(benzimidazol-1-yl)-5-cyanopyrimidine

HRID 2300825Notes

Reaction equation

HRID 2300825 reaction equation
[H-].[Na+].[N:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[NH:5][CH:4]=1.[CH2:12]([S:14][C:15]1[N:20]=[C:19](Cl)[C:18]([C:22]#[N:23])=[CH:17][N:16]=1)[CH3:13]>CN(C=O)C.O>[CH2:12]([S:14][C:15]1[N:16]=[C:17]([N:3]2[C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=3[N:5]=[CH:4]2)[C:18]([C:22]#[N:23])=[CH:19][N:20]=1)[CH3:13]

Participants

6

Reactant 3

HCID 5798BenzimidazoleHCID 24758Sodium hydrideHCID 183753954-Chloro-2-(ethylthio)pyrimidine-5-carbonitrile

Product 1

HCID 183759622-Ethylthio-4-(benzimidazol-1-yl)-5-cyanopyrimidineYield 68.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a suspension of sodium hydride (31 mg, 0.78 mmol) in DMF (2.5 mL) at 0° C. was added benzimidazole (86 mg, 0.72 mmol). After stirring for 5 min, the reaction mixture was warmed to room temperature. To this was added 2-ethylthio-4-chloro-5-cyanopyrimidine (130 mg, 0.65 mmol) dissolved in DMF (1.0 mL), then the mixture was heated at 100° C. for 1 h. The reaction mixture was cooled and carefully diluted with H2O. The aqueous layer was extracted with EtOAc several times, and the combined extracts were washed with brine. After drying over Na2SO4, the crude material was purified by flash chromatography using 1:7 acetone:hexane system to give 126 mg of the title compound. Mass spectrum 282.2 (ESI, M+1).

Workup

  1. temperaturethe mixture was heated at 100° C. for 1 h
  2. temperatureThe reaction mixture was cooled
  3. extractionThe aqueous layer was extracted with EtOAc several times
  4. washthe combined extracts were washed with brine
  5. dry with materialAfter drying over Na2SO4
  6. customthe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-74e33135689a43e28445ef4660cd15bc
Source dataset
uspto-grants-2002_12
Patent number
US06498165B1

Reaction notes

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