반응 단계
tert-Butyl isocyanide (538 mg, 0.73 mL, 6.48 mmol) was added to a stirred slurry of 1-(5′-chloro-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)-pent-4-en-1-one (900 mg, 3.24 mmol) and ammonium acetate (1.0 g, 12.96 mmol) in 2,2,2-trifluoroethanol (0.5 mL). After stirring at room temperature for 5 days, the reaction mixture was poured into water and extracted with ethyl acetate (3×). The combined organic phase was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. Purification by flash column chromatography (silica gel, 10-40% ethyl acetate in heptane) gave the title compound as a white solid (1.02 g, 74%); 1H NMR (CDCl3, 300 MHz) δ 8.06 (dd, J1=2.5 Hz, J2=0.5 Hz, 1H), 7.37 (dd, J1=9 Hz, J2=2.5 Hz, 1H), 7.01 (br s, NH, 1H), 6.55 (dd, J1=9.0 Hz, J2=0.5 Hz, 1H), 5.78 (m, 1H), 5.50 (br s, NH, 1H), 4.97 (m, 2H), 4.38 (m, 1H), 4.14 (m, 1H), 3.00 (ddd, J1=14.5 Hz, J2=11.5 Hz, J3=5.0 Hz, 1H), 2.72 (td, J1=13 Hz, J2=2.5 Hz, 2H), 2.44 (tt, J1=2.5 Hz, J2=3 Hz, 1H), 1.97-2.08 (m, 1H), 2.00 (s, 3H), 1.80 (m, 3H), 1.20-1.52 (m, 3H) and 1.30 (s, 9H).
