反应详情

To a solution of nicotinic acid (454 mg, 3.69 mmol) in DMF (33 mL) were added successively TBTU (1.18 g, 3.69 mmol), N,N-diisopropylethylamine (3.16 mL, 18.4 mmol) and 5-bromo-6-(2,2,2-trifluoroethoxy)pyridin-3-amine (1 g, 3.69 mmol). The brown mixture was stirred under argon for 3 h at room temperature. After evaporation of DMF, the brown oil was partitioned between ethyl acetate (50 mL) and 1M NaOH (30 mL). The aqueous layers were back-extracted with ethyl acetate (1×50 mL). The organic parts were washed with water (2×25 mL) and brine (25 mL), then dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 10% to 100% ethyl acetate in heptane) to deliver the desired product as a white solid (580 mg; 42%); MS (EI): 376.1; 378.0 (M+H).

1. customAfter evaporation of DMF
2. customthe brown oil was partitioned between ethyl acetate (50 mL) and 1M NaOH (30 mL)
3. extractionThe aqueous layers were back-extracted with ethyl acetate (1×50 mL)
4. washThe organic parts were washed with water (2×25 mL) and brine (25 mL)
5. dry with materialdried over MgSO4
6. concentrationconcentrated in vacuo
7. customThe crude material was purified by flash chromatography (silica gel, 40 g, 10% to 100% ethyl acetate in heptane)