Triethylamine → HCID 178503265, compound

Participants

Reaction Steps

2-(4-Methylsulfanyl-phenoxy)-nicotinic acid (500 mg, 1.91 mmol) was dissolved in dimethylformamide (10 ml) and triethylamine (800 μl, 5.74 mmol) was added followed by cis-4-aminocyclohexanol hydrochloride (290 mg, 1.91 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (404 mg, 2.10 mmol) and 1-hydroxybenzotriazole (284 mg, 2.10 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 sat. sodium bicarbonate solution (25 ml) and ethyl acetate (20 ml) and the aqueous phase was extracted with ethyl acetate (2×20 ml). The combined organic extracts were washed with water (10 ml), brine (10 ml), dried over MgSO4 and the solvent was removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of dichloromethane:methanol:concentrated aqueous ammonia (97.5:2.5:0.25 changing to 97:3:0.3, by volume) to give N-(cis-4-hydroxy-cyclohexyl)-2-(4-methylsulfanyl-phenoxy)-nicotinamide (620 mg) as a white solid.

Provenance & Evidence