Dimethylformamide → HCID 59331560, compound

Participants

Reaction Steps

To a solution of 6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine-3-carboxylic acid (0.500 g) in N,N-dimethylformamide (10 mL) were added N-methoxymethanamine hydrochloride (152 mg), triethylamine (0.436 mL), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (300 mg) and 1-hydroxybenzotriazole (239 mg), and the mixture was stirred at room temperature for 16 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (ethyl acetate:hexane=30:70-100:0, volume ratio) to give a colorless oil. A solution of the obtained oil in tetrahydrofuran (5 mL) was purged with nitrogen, and a 1.0M methylmagnesium bromide tetrahydrofuran solution (1.5 mL) was added under ice-cooling. The reaction solution was warmed to room temperature, and stirred at room temperature for 16 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70-100:0, volume ratio) to give a colorless oil. A solution of the obtained oil in tetrahydrofuran (3 mL) was purged with nitrogen, a 1.0M methylmagnesium bromide tetrahydrofuran solution (5.0 mL) was added under ice-cooling, and the mixture was stirred at 0° C. for 4 hr. A saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=30:70-100:0, volume ratio) and recrystallized from hexane-ethyl acetate to give the title compound (0.096 g, yield 19%) as colorless crystals. MS: 495 (MH+). melting point 112-114° C.

Provenance & Evidence