反应详情

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).

1. extractionextracted with ethyl acetate (3×)
2. washThe combined organic phase was washed with saturated aqueous sodium chloride
3. dry with materialdried over anhydrous magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customPurification by flash column chromatography (silica gel, 10-40% ethyl acetate in heptane)