反应详情

EDC (1.3 equiv.) was added to a solution of 5-bromo-6-methylpyridin-3-amine (1.05 equiv), 2-(2-cyanopropan-2-yl)isonicotinic acid (1.0 equiv), HOAt (1.3 equiv) in DMF (0.17 M). The mixture was stirred at ambient temperature 3 hrs. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine, dried over sodium sulfate, filtered, and concentrated. The crude was purified by ISCO(50% EtOAc/Heptane). Combined fractions still contained 17% 5-bromo-6-methylpyridin-3-amine. Add 2-(2-cyanopropan-2-yl)isonicotinic acid (0.3 equiv), EDC (0.3 equiv), HOAt (0.3 equiv) in DMF (0.17 M). After stirred at rt overnight, the reaction mixture was diluted with water and extracted with ethyl acetate. The combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine, dried over sodium sulfate, filtered, and concentrated to yield N-(5-bromo-6-methylpyridin-3-yl)-2-(2-cyanopropan-2-yl)isonicotinamide in 71% over three steps. LCMS (m/z) (M+H)=359.0, Rt=0.73 min.

1. extractionextracted with ethyl acetate
2. washThe combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude was purified by ISCO(50% EtOAc/Heptane)
7. stirringAfter stirred at rt overnight
8. extractionextracted with ethyl acetate
9. washThe combined extracts were washed sequentially with 1M aqueous sodium hydroxide and brine
10. dry with materialdried over sodium sulfate
11. filtrationfiltered
12. concentrationconcentrated