Imidazole → HCID 22310820, compound

Participants

Reaction Steps

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.

Provenance & Evidence