5-bromo-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamide → 5-cyano-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-bromo-3-methyl-N-(pyridin-3-ylmethyl)thiophene-2-carboxamide (1.92 g, 6.17 mmol) and copper cyanide (2.21 g, 24.68 mmol) in anhydrous N,N-dimethylformamide (25 mL) was stirred under nitrogen atmosphere at 150° C. for 18 h. The reaction mixture was allowed to cool to ambient temperature, and partitioned between ethyl acetate (200 mL) and 14% aqueous ammonium hydroxide solution (200 mL). The aqueous layer was extracted with ethyl acetate (100 mL), and combined organic layer was washed with water (2×100 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluted with 7% methanol in dichloromethane to afford the title compound as an off-white solid (0.72 g, 45%): 1H NMR (300 MHz, CDCl3) δ 8.60 (s, 1H), 8.57 (s, 1H), 7.71 (dd, J=7.8, 7.8 Hz, 1H), 7.39 (s, 1H), 7.30 (m, 1H), 6.31 (br s, 1H), 4.63 (d, J=5.9 Hz, 2H), 2.50 (s, 3H); MS (ES+) m/z 258.2 (M+1).

Provenance & Evidence