反应详情

温度

150 °C

5-(tert-Butoxycarbonylamino)-2-chloroisonicotinic acid (502 mg, 1.84 mmol) was suspended in polyphosphoric acid (9.5 g, 102 mmol) at ambient temperature and stirred for 10 mins causing a bright yellow coloration and visible evolution of gas. 2′-Chloroacetophenone (570 mg, 3.69 mmol) was added and the mixture heated to 150° C. for 2.5 h. The mixture was diluted with cold water (50 mL), and then cooled in ice and treated with solid sodium hydroxide (6.0 g, 150 mmol) to pH ˜7. The mixture was filtered and the recovered oily solids washed with water, dissolved in methanol and reconcentrated in vacuo. The residue was purified by flash chromatography (silica, ISCO, 0.5-20% methanol in DCM) to afford the title compound as a cream solid (29.2 mg, 5.5%). 1H NMR (400 MHz, MeOD) δ 8.87 (s, 1H), 8.12 (s, 1H), 7.64-7.58 (m, 2H), 7.58-7.46 (m, 2H), 6.47 (s, 1H); NH absent. LCMS: M+H+=291 & 293.

1. temperaturecooled in ice
2. filtrationThe mixture was filtered
3. washthe recovered oily solids washed with water
4. dissolutiondissolved in methanol
5. customThe residue was purified by flash chromatography (silica, ISCO, 0.5-20% methanol in DCM)