Reaction Steps
To a solution of 3-(6-bromopyridin-2-yl)-2-cyano-N-(1-(4-hydroxyphenyl)butyl)acrylamide (21 mg, 0.05 mmol) in acetone was added MeI (32.6 μL, 0.52 mmol) and potassium carbonate powder (7.25 mg, 0.05 mmol). The resulting mixture was stirred at room temperature for 4 hours before the addition of ethyl acetate. The organic solution was then washed with water (1×), saturated brine (1×), dried over sodium sulfate and concentrated to give a yellow oil as the crude product. The crude material was purified with preparative TLC plate to afford (E)-3-(6-bromopyridin-2-yl)-2-cyano-N-(1-(4-methoxyphenyl)butyl)acrylamide (8) as a light yellow solid (9.2 mg, 42% yield) and (Z)-3-(6-bromopyridin-2-yl)-2-cyano-N-(1-(4-methoxyphenyl)butyl)acrylamide (9) as a white solid (4.4 mg, 20% yield). Mass spec ES+, m/z=414.0 (m+H+). E-isomer (8): 1H NMR (500 MHz, CDCl3/CD3OD) δ 7.59 (t, J=7.7, 1H), 7.52 (d, J=8.0, 1H), 7.27 (d, J=8.7, 2H), 7.22 (d, J=7.4, 1H), 6.83 (d, J=8.9, 2H), 6.81 (s, 1H), 3.89-3.83 (m, 2H), 3.81 (s, 3H), 1.65 (dd, J=15.4, 7.9, 2H), 1.39 (dd, J=15.1, 7.5, 2H), 0.94 (t, J=7.4, 3H). Z-isomer (9): 1H NMR (500 MHz, CDCl3) δ 7.83 (s, 1H), 7.79 (d, J=7.6, 1H), 7.61 (t, J=7.8, 1H), 7.52 (d, J=7.9, 1H), 7.15 (d, J=8.8, 2H), 6.93 (d, J=8.8, 2H), 3.84 (s, 3H), 3.84-3.79 (m, 2H), 1.57 (dd, J=14.8, 7.1, 5H), 1.37 (dq, J=15.0, 7.5, 2H), 0.94 (t, J=7.4, 3H).
