1-Hydroxybenzotriazole → 5-fluoro-N-(1-hydroxymethyl-cyclohexyl)-2-(3-methylsulfanyl-phenoxy)-nicotinamide

A solution of (1-aminocyclohexyl)-methanol (R. J. W. Cremlyn et al J. Chem. Soc Perkins I, 1972, 1727) (130 mg, 0.78 mmol) and triethylamine (300 μl) in dimethylformamide (5 ml) was added to a solution of 5-fluoro-2-(3-methylsulfanyl-phenoxy)-nicotinic acid (218 mg, 0.78 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (165 mg, 0.86 mmol) and 1-hydroxybenzotriazole (116 mg, 0.86 mmol) in dimethylformamide (4 ml) and the reaction was stirred under nitrogen at room temperature for 64 h. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned between ethyl acetate (25 ml) and water (25 ml). The organic phase was removed and washed with sat. sodium bicarbonate solution (25 ml) followed by 1M citric acid (25 ml) and brine (25 ml). The organic layer was 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 ethyl acetate:pentane (20:80 changing to 30:70 then 50:50, by volume) to give 5-fluoro-N-(1-hydroxymethyl-cyclohexyl)-2-(3-methylsulfanyl-phenoxy)-nicotinamide (191 mg) as a colourless oil.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. customthe residue was partitioned between ethyl acetate (25 ml) and water (25 ml)
3. customThe organic phase was removed
4. washwashed with sat. sodium bicarbonate solution (25 ml)
5. dry with materialThe organic layer was dried over MgSO4
6. customthe solvent was removed under reduced pressure
7. customThe residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of ethyl acetate:pentane (20:80 changing to 30:70

ORD record

ord-642b4c3a222e4760948a6043c23257ba

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07141586B2