反应详情

温度

0 °C

Phenyl chloroformate (0.98 mL, 7.8 mmol) was dissolved in CH2Cl2, cooled down to 0° C. and 5-aminobenzimidazole (0.865 g, 6.5 mmol) was added slowly. The mixture was kept at 0° C. for 30 min and then the mixture was allowed to adapt ambient temperature. The mixture was stirred at ambient temperature for 2 h. The resulting solid was withdrawn by suction, dried and taken up in a small amount of DMF. To the solution, 1-amino-3,3-dimethylbutan-2-one (0.986, 6.5 mmol) and TEA (2.73 mL, 19.5 mmol) were added. The mixture was kept at 40° C. for 2 h. The solvent was removed and purified by means of preparative HPLC. The remains were re-dissolved in MeOH and a small amount of HCl was added (1-2%). The solution was subjected to hydrogenation (PdC, 10% on charcoal, 4 bar, 60° C.) for 4 h. The catalyst was removed by filtration through a pad of CELITE® and the residue was washed with water. The organic layer was dried, filtrated and the solvent was removed to result in the final product. Yield: 0.087 g (6.3%); MS m/z 259.4 (M+H)+; 1H NMR (DMSO, 400 MHz): δ 0.72 (s, 9H); 3.23-3.27 (m, H); 3.46-3.50 (m, H); 4.37-4.41 (m, H); 6.84 (bs, H); 7.56 (dd, H, 3J=9.1 Hz, 4J=1.7 Hz); 7.70 (d, H, J=9.1 Hz); 7.81 (d, H, 4J=1.7 Hz); 9.27 (s, H), HPLC (λ=214 nm, [B]: rt 6.83 min (99%).

1. customto adapt ambient temperature
2. customThe resulting solid was withdrawn by suction
3. customdried
4. waitThe mixture was kept at 40° C. for 2 h
5. customThe solvent was removed
6. custompurified by means of preparative HPLC
7. dissolutionThe remains were re-dissolved in MeOH
8. additiona small amount of HCl was added (1-2%)
9. waitThe solution was subjected to hydrogenation (PdC, 10% on charcoal, 4 bar, 60° C.) for 4 h
10. customThe catalyst was removed by filtration through a pad of CELITE®
11. washthe residue was washed with water
12. customThe organic layer was dried
13. filtrationfiltrated
14. customthe solvent was removed