Pyridine → N-cyclohexyl-N-methyl-4-(pyridin-3-yl)-1H-imidazole-1-carboxamide

HRID 530300Notes

Reaction equation

HRID 530300 reaction equation
Cl.Cl.[NH:3]1[CH:7]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[N:5]=[CH:4]1.CC([O-])(C)C.[K+].N1C=CC=CC=1.[CH:26]1([N:32]([CH3:36])[C:33](Cl)=[O:34])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1>O1CCCC1.CN(C=O)C.CN(C)C1C=CN=CC=1.O>[CH:26]1([N:32]([CH3:36])[C:33]([N:3]2[CH:7]=[C:6]([C:8]3[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=3)[N:5]=[CH:4]2)=[O:34])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1

Participants

9

Reactant 4

HCID 1049PyridineHCID 15209947N-cyclohexyl-N-methylcarbamoyl chlorideHCID 23665647Potassium tert-butoxideHCID 178478555HCID 178478555, compound

Product 1

HCID 66554294N-cyclohexyl-N-methyl-4-(pyridin-3-yl)-1H-imidazole-1-carboxamide

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred suspension of 3-(1H-imidazol-4-yl)pyridine dihydrochloride (1.745 g, 8 mmol) in a mixture of tetrahydrofuran (29 mL) and DMF (2.90 mL) was added potassium 2-methylpropan-2-olate (1.795 g, 16.0 mmol) and the mixture was refluxed for 30 minutes. The resulting brown suspension was cooled to room temperature and treated with pyridine (0.979 mL, 12 mmol) and N,N-dimethylpyridin-4-amine (0.098 g, 0.8 mmol), followed by the addition of cyclohexyl(methyl)carbamic chloride (1.476 g, 8.4 mmol). The reaction was heated to 90° C. overnight, whereupon the mixture was diluted with water and extracted with ethyl acetate. The organic phase was dried (MgSO4) and filtered. After evaporation, the crude product was chromatographed over silica gel using a dichloromethane/methanol (9:1) mixture. Homogenous fractions were pooled and evaporated to leave a white powder, (160 mg, 7%).

Workup

  1. temperaturethe mixture was refluxed for 30 minutes
  2. temperatureThe reaction was heated to 90° C. overnight, whereupon the mixture
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic phase was dried (MgSO4)
  5. filtrationfiltered
  6. customAfter evaporation
  7. customthe crude product was chromatographed over silica gel using a dichloromethane/methanol (9:1) mixture
  8. customevaporated
  9. customto leave a white powder, (160 mg, 7%)

Sources & evidence

ORD record
ord-37c6e3b4cc5f41a99746f2b94244b462
Source dataset
uspto-grants-2016_05
Patent number
US09353082B2

Reaction notes

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