反应详情

温度

60 °C

To a solution of 6-[(1S)-1,3-dihydroxy-1-(1H-imidazol-4-yl)propyl]-N-methyl-2-naphthamide (1.0 g, 3.1 mmol) in tetrahydrofuran (100 mL) were added N-ethyldiisopropylamine (2.39 g, 18.4 mmol) and methanesulfonyl chloride (2.11 g, 18.4 mmol) at room temperature. The mixture was stirred at the same temperature for 3 hr. To the reaction mixture was added a solution of sodium carbonate (1.31 g, 12.3 mmol) in water (3 mL). The mixture was heated to 60° C. and stirred for 5 hr. After the reaction mixture was allowed to cool to room temperature, ethyl acetate (25 mL) was added thereto. The organic layer was separated and concentrated under reduced pressure. Methanol (16.7 mL) and water (6.4 mL) were added to the residue. The mixture was heated to 65° C., and activated carbon (45 mg) was added thereto. After stirring at the same temperature for 30 min, the activated carbon was filtered off and washed with methanol (1.1 mL). Water (6.4 mL) was added to the filtrate at 55° C. The resulting mixture was allowed to cool to room temperature and stirred for 30 min. To the mixture was added water (6.4 mL) at the same temperature, and the mixture was stirred for 2 hr. The mixture was cooled to 0° C. and stirred for 2 hr. The obtained precipitated crystals were collected by filtration, washed with 45% aqueous methanol (3 mL), and dried under reduced pressure to give 6-((7S)-hydroxy-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-7-yl)-N-methyl-2-naphthamide (540 mg, 1.8 mmol). yield 57%.

1. stirringstirred for 5 hr
2. temperatureto cool to room temperature
3. customThe organic layer was separated
4. concentrationconcentrated under reduced pressure
5. additionMethanol (16.7 mL) and water (6.4 mL) were added to the residue
6. temperatureThe mixture was heated to 65° C.
7. additionactivated carbon (45 mg) was added
8. stirringAfter stirring at the same temperature for 30 min
9. filtrationthe activated carbon was filtered off
10. washwashed with methanol (1.1 mL)
11. additionWater (6.4 mL) was added to the filtrate at 55° C
12. temperatureto cool to room temperature
13. stirringstirred for 30 min
14. additionTo the mixture was added water (6.4 mL) at the same temperature
15. stirringthe mixture was stirred for 2 hr
16. temperatureThe mixture was cooled to 0° C.
17. stirringstirred for 2 hr
18. customThe obtained precipitated crystals
19. filtrationwere collected by filtration
20. washwashed with 45% aqueous methanol (3 mL)
21. customdried under reduced pressure