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温度

0 °C

Concentrated sulfuric acid (0.95 ml, 17.2 mmol, 0.5 equiv) is added to a solution of 6-aminonicotinic acid (5.0 g, 34.4 mmol) in ethanol (50 ml). After heating to reflux for 16 hours, the reaction mixture is carefully poured into a concentrated aqueous Na2CO3 solution. The aqueous phase is extracted three times with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue is dissolved in anhydrous THF (25 ml). At −60° C., lithium aluminium hydride (2.68 g, 68.6 mmol, 3.0 equiv) is carefully added. The mixture is warmed to 0° C., and then refluxed for 1 hour. After cooling, water (1.5 ml) and 5 N aqueous NaOH solution (1.5 ml) are added. The precipitate is filtered off, and the filtrate is concentrated in vacuo. The residue is purified via flash chromatography (EtOAc/MeOH 95:5) to afford the title compound (2.15 g, 72%). 1H NMR (400 MHz, d6-DMSO): δ=7.82 (d, J=1.7 Hz, 1H), 7.32 (dd, J=8.3/2.5 Hz, 1H), 6.40 (dd, J=9.3/1.0 Hz, 1H), 5.77 (br s, 2H), 4.88 (t, J=5.5 Hz, 1H), 4.27 (d, J=5.5 Hz, 2H), MS (ES+): 125 (M+H)+.

1. temperatureAfter heating
2. temperatureto reflux for 16 hours
3. extractionThe aqueous phase is extracted three times with EtOAc
4. washThe combined organic layers are washed with brine
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. dissolutionThe residue is dissolved in anhydrous THF (25 ml)
9. temperaturerefluxed for 1 hour
10. temperatureAfter cooling
11. filtrationThe precipitate is filtered off
12. concentrationthe filtrate is concentrated in vacuo
13. customThe residue is purified via flash chromatography (EtOAc/MeOH 95:5)