Sodium hydride → tert-Butyl {2-[1-(6-cyanopyridin-2-ylmethyl)-2-(1-methylcyclopropyl)-2-oxoethyl]-5-methoxyphenyl}carbamate

Participants

Reaction Steps

Under an argon atmosphere, to a solution of tert-butyl {5-methoxy-2-[2-(1-methylcyclopropyl)-2-oxoethyl]phenyl}carbamate (300 mg) in N,N-dimethylformamide (3.1 mL) was added sodium hydride (50-72% in oil, 50 mg) under ice-cooling, and the mixture was stirred for 1 hour. 6-(Chloromethyl)pyridine-2-carbonitrile (158 mg) was added thereto in one portion, and the mixture was gradually warmed to room temperature. 13 Hours later, to the reaction mixture were added a saturated aqueous ammonium chloride solution and water, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine successively, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (271 mg). 1H-NMR (CDCl3) δ ppm: 0.62-0.73 (2H, m), 1.22-1.30 (5H, m), 1.57 (9H, s), 3.21 (1H, dd, J=8.2, 15.7 Hz), 3.54 (1H, dd, J=6.7, 15.7 Hz), 3.78 (3H, s), 4.68-4.78 (1H, m), 6.54-6.61 (1H, m), 6.95 (1H, d, J=8.5 Hz), 7.18-7.25 (1H, m), 7.33-7.40 (1H, m), 7.48-7.55 (1H, m), 7.64 (1H, t, J=7.8 Hz), 7.82 (1H, br s).

Provenance & Evidence