Sodium Iodide → N-[1-({5-Chloro-2-[(phenylmethyl)oxy]phenyl}methyl)-1H-pyrazol-4-yl]-2,6-difluorobenzamide

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Reaction Steps

2,6-Difluoro-N-1H-pyrazol-4-ylbenzamide (for a preparation see Intermediate 2; 86 mg, 0.385 mmol) was dissolved in DMF (2.5 ml), sodium iodide (21 mg, 0.140 mmol), potassium carbonate (169 mg, 1.22 mmol) and 2-(bromomethyl)-4-chloro-1-[(phenylmethyl)oxy]benzene (synthesised according to Bioorganic & Medicinal Chemistry Letters (2009), 19, 2599-2603; 121 mg, 0.388 mmol) were then added using further DMF (2.5 ml). The reaction was then stirred overnight. Further 2-(bromomethyl)-4-chloro-1-[(phenylmethyl)oxy]benzene (125 mg) was added and the reaction was stirred for 4 h. The reaction was concentrated in vacuo. The crude material was treated with water (50 ml) and the aqueous solution was extracted with ethyl acetate (3×50 ml). The combined organic extracts were dried (MgSO4) and concentrated in vacuo. The sample was loaded in ethyl acetate and purified on silica (20 g) using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound (70 mg) as a colourless gum; LCMS (System 1): MH+=454, tRET=3.59 min.

Provenance & Evidence