反应详情

温度

50 °C

Triethylamine (0.47 mL, 3.38 mmol) was added to 5-aminoimidazole-4-carboxamide hydrochloride (0.50 g, 3.1 mmol) in anhydrous methanol (12 mL). The reaction mixture was stirred for 10 min and 6-phenoxynicotinaldehyde (0.74 g, 3.7 mmol) and acetic acid (0.09 mL, 1.57 mmol) were added. The dark solution was stirred over night and sodium cyanoborohydride (0.23 g, 3.7 mmol) was added. More sodium cyanoborohydride (0.15 g, 2.4 mmol) was added after 40 min and the mixture was stirred for another 3 h. The reaction mixture was heated at 50° C. for 3 h, sodium cyanoborohydride (0.15 g, 2.4 mmol) was added and the mixture was heated at 50° C. over night. Sodium borohydride (0.12 g, 3.2 mmol) was added and the mixture was heated at 50° C. for 1 h, more sodium borohydride (0.15 g, 4.0 mmol) and NMP (1.0 mL) were added and the mixture was heated at 60° C. for 3.5 h. After cooling, NaHCO3 (sat., 20 mL) was added and some of the methanol was removed in vacuo. The mixture was extracted with EtOAc, the organic phase was extracted with 1N HCl (2×30 mL) and the acidic phase was made basic with 2N NaOH and was extracted with DCM. The organic phase was dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography on silica (0 to 10% MeOH in DCM+NH3) to yield 0.25 g (0.81 mmol, 26%) of a slightly green syrup.

1. stirringThe dark solution was stirred over night
2. stirringthe mixture was stirred for another 3 h
3. temperaturethe mixture was heated at 50° C. over night
4. temperaturethe mixture was heated at 50° C. for 1 h
5. temperaturethe mixture was heated at 60° C. for 3.5 h
6. temperatureAfter cooling
7. customsome of the methanol was removed in vacuo
8. extractionThe mixture was extracted with EtOAc
9. extractionthe organic phase was extracted with 1N HCl (2×30 mL)
10. extractionwas extracted with DCM
11. dry with materialThe organic phase was dried over MgSO4
12. filtrationfiltered
13. concentrationconcentrated
14. customThe crude product was purified by column chromatography on silica (0 to 10% MeOH in DCM+NH3)
15. customto yield 0.25 g (0.81 mmol, 26%) of a slightly green syrup