反应详情

温度

100 °C

To a stirred solution of methyl 3,4,6-trichloropyridine-2-carboxylate (310 mg, 1.29 mmol) in DMF (5 ml) was added TEA (359 μl, 2.58 mmol) followed by tert-butyl 4-(methylamino)piperidine-1-carboxylate (276 mg, 1.29 mmol) and the reaction mixture was heated at 100° C. for 4 h. The reaction mixture was then cooled to room temperature and poured onto water (50 ml), followed by extraction of the product into TBME (3×50 ml), washing of the combined organics with brine (50 ml), drying with Na2SO4 and evaporation. The crude product was then purified over a 10 g silica Isolute column eluting with a gradient of 0% to 50% EtOAc in heptane to afford the title compound as a white solid (95 mg, 18%). LC-MS 95%, 2.29 min (3.5 minute LC-MS method), m/z=418.1/419.8, 1H NMR (500 MHz, Chloroform-d) δ 6.87 (s, 1H) 4.12-4.34 (m, 2H) 3.99 (s, 3H) 3.69-3.80 (m, 1H) 2.79 (s, 3H) 2.64-2.77 (m, 2H) 1.75 (br. s., 4H) 1.48 (s, 9H).

1. temperatureThe reaction mixture was then cooled to room temperature
2. additionpoured onto water (50 ml)
3. extractionfollowed by extraction of the product into TBME (3×50 ml)
4. washwashing of the combined organics with brine (50 ml)
5. dry with materialdrying with Na2SO4 and evaporation
6. customThe crude product was then purified over a 10 g silica Isolute column
7. washeluting with a gradient of 0% to 50% EtOAc in heptane