反应详情

温度

80 °C

Chloroacetaldehyde (˜50% in H2O, 3.24 ml, 26 mmol) was added to a stirred mixture of 2-amino-isonicotinonitrile (1.6 g, 3.4 mmol) and NaHCO3 (2.23 g, 26.5 mmol) in ethanol (20 ml) at RT under N2. The reaction was stirred and heated at 80° C. for 18 hours. After cooling to RT the volatiles were removed in vacuo and the residue was partitioned between EtOAc/H2O. This mixture was filtered to remove some dark insoluble residue. The solid was washed with MeOH. The aqueous layer was extracted with EtOAc (×2). The combined EtOAc extracts were dried (Na2SO4) and filtered. The MeOH washings were added and the volatiles were removed in vacuo. The residue was purified by chromatography on silica: 100% DCM→1% 2M NH3-MeOH/DCM to give the title product. 1H NMR (400 MHz, DMSO-d6): 8.74 (1H, dd), 8.35 (1H, s), 8.19 (1H, s), 7.86 (1H, s), 7.21 (1H, dd).

1. temperatureAfter cooling to RT the volatiles
2. customwere removed in vacuo
3. customthe residue was partitioned between EtOAc/H2O
4. filtrationThis mixture was filtered
5. customto remove some dark insoluble residue
6. washThe solid was washed with MeOH
7. extractionThe aqueous layer was extracted with EtOAc (×2)
8. dry with materialThe combined EtOAc extracts were dried (Na2SO4)
9. filtrationfiltered
10. additionThe MeOH washings were added
11. customthe volatiles were removed in vacuo
12. customThe residue was purified by chromatography on silica