Imidazole → HCID 22310820, compound

HRID 967047Notes

Reaction equation

HRID 967047 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.C(=O)([O-])[O-].[Cs+].[Cs+].[N+]([C:15]1[CH:20]=[CH:19][N:18]=[C:17]([C:21]#[N:22])[C:16]=1[O:23][CH3:24])([O-])=O>CN(C=O)C>[N:1]1([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([C:21]#[N:22])[C:16]=2[O:23][CH3:24])[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 10796Cesium carbonateHCID 22310829HCID 22310829, compound

Product 1

HCID 22310820HCID 22310820, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 0.2 g (0.51 mmol) 2-{N-meta-[4-(trifluoromethylphenoxy)phenyl]} aminocarbonyl-3-hydroxy-4-amino pyridine (prepared according to the method described in WO 0149666) and 78 mg (0.56 mmol) of 2,5-dimethoxytetrahydrofuran) in 1 ml of glacial acetic acid, is heated at 110° C. for 1 hour. The reaction is cooled and solvent evaporated, the residue is dissolved in dichloromethane and washed with aqueous sodium bicarbonate, the organic phase was dried over MgSO4 and solvent evaporated. The crude product was chromatographed on silica to yield 137 mg (61% yield) of a yellow solid. (M+1=440) 2-N-(3-trifluoromethyl phenyl) aminocarbonyl-3-hydroxy-4-(imidazol-1-yl) pyridine (compound 2-24) A mixture of 1.36 g (20 mmol) of imidazol and 60.52 g (20 mmol) of cesium carbonate is stirred at room temperature in 20 ml of DMF for 20 minutes. 3.58 g (20 mmol) of 4-nitro-3-methoxy-2-cyano pyridine (prepared according to the methods described in WO 0149667) is added in one pot and the mixture is stirred overnight. DMF is removed in vacuo and the residue is partitioned between water and ethyl acetate. The aqueous phase is further extracted with ethyl acetate. The organic phases are washed with dilute brine, dried and solvent evaporated. Purification on silica gave 1.4 g of 4-(imidazol-1-yl)-3-methoxy-2-cyano pyridine.

Workup

  1. additionis added in one pot
  2. customDMF is removed in vacuo
  3. customthe residue is partitioned between water and ethyl acetate
  4. extractionThe aqueous phase is further extracted with ethyl acetate
  5. washThe organic phases are washed with dilute brine
  6. customdried
  7. customsolvent evaporated
  8. customPurification on silica

Sources & evidence

ORD record
ord-df51a4841a4f44cd96d854da933dfd85
Source dataset
uspto-grants-2005_10
Patent number
US06953807B2

Reaction notes

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