2-[3-(Methylsulfanyl)phenoxy]-5-fluoronicotinic acid (100 mg, 0.358 mmol) was dissolved in dimethylformamide (5 ml) and triethylamine (250 μl, 3.41 mmol) was added followed by 2-amino-1-methylcyclohexanol hydrochloride (65 mg, 0.39 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (205 mg, 1.07 mmol) and 1-hydroxybenzotriazole (53 mg, 0.39 mmol). The reaction was stirred under nitrogen at room temperature for 18 h and the solvent was removed under reduced pressure. The residue was partitioned between 10% aq. citric acid solution and diethyl ether. The organic was washed with sat. sodium bicarbonate solution, water and brine, dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography using ethyl acetate:cyclohexane (5:95 to 50:50) as eluant to give 5-fluoro-N-(2-hydroxy-2-methylcyclohexyl)-2-[3-(methylsulfanyl)phenoxy]nicotinamide (140 mg) as a gum.
