Cyanogen Bromide → 5-(4-{1,2-Dimethyl-1-[4-(1-methyl-1-pyridin-2-ylethoxy)phenyl]propyl}phenyl)-1,3,4-oxadiazol-2-amine

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Reaction Steps

Hydrazine monohydrate (10 equiv.) is added to a stirred solution of 5g (1 equiv.) in ethanol and the resulting solution heated at reflux until 5g is consumed. After cooling to room temperature, the volatiles are removed in vacuo, and the residue is partitioned between EtOAc and water. The organic phase is separated, washed three times with water, brine, dried (MgSO4) and concentrated in vacuo. The crude residue is dissolved in dioxane to which aqueous sodium bicarbonate (1.1 equiv) in water is added dropwise via syringe. A solution of cyanogen bromide (1.1 equiv.) in dioxane is then added slowly, and the resulting mixture is aged at ambient temperature until the reaction is deemed complete. The reaction mixture is poured into saturated aqueous sodium bicarbonate and extracted three times with EtOAc. The combined organic extracts are washed with brine, dried (MgSO4) and concentrated in vacuo. Purification of the crude residue by flash chromatography on silica gel affords the title compound 5h. If desired, 5h can be resolved into its enantiomeric components using preparative chiral HPLC techniques.

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