反应详情

To a solution of 4-[(2-hydroxybutylamino)methyl]benzenesulfonamide hydrochloride (842 mg) and 2-benzoyl-4-bromobenzoic acid (915 mg) and 1-hydroxy-1H-benzotriazole (643 mg) in DMF (20 ml) was added triethylamine (1.25 ml) and then WSC (1.03 g) was added at room temperature, and the mixture was stirred at room temperature for 15 hrs. The solvent was evaporated under reduced pressure, and the residue was partitioned between dichloromethane and water, washed with 1N hydrochloric acid, aqueous sodium hydrogen carbonate and brine and dried by adding sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=1/1→1/9). The obtained colorless amorphous form was dissolved in dichloromethane (20 ml) and 4-methylmorpholine N-oxide (612 mg) and molecular sieves 4A (500 mg) were added. Under ice-cooling, tetra-n-propylammonium perruthenate (31 mg) was added, and the mixture was stirred at room temperature for 3 hrs. The molecular sieves 4A was removed from the reaction solution by filtration. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=7/3→1/1). The obtained colorless amorphous form was dissolved in ethanol (20 ml) and 1,8-diazabicyclo[5.4.0]-7-undecene (0.84 ml) was added. The mixture was heated under reflux for 12 hrs. The solvent was evaporated under reduced pressure, and the residue was partitioned between ethyl acetate and 1N hydrochloric acid, washed with aqueous sodium hydrogen carbonate and brine and sodium sulfate was added to dry the mixture. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=7/3→1/1) to give the title compound (267 mg, 17%).

1. customThe solvent was evaporated under reduced pressure
2. customthe residue was partitioned between dichloromethane and water
3. washwashed with 1N hydrochloric acid, aqueous sodium hydrogen carbonate and brine
4. customdried
5. additionby adding sodium sulfate
6. customThe solvent was evaporated under reduced pressure
7. customthe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=1/1→1/9)
8. dissolutionThe obtained colorless amorphous form was dissolved in dichloromethane (20 ml)
9. addition4-methylmorpholine N-oxide (612 mg) and molecular sieves 4A (500 mg) were added
10. temperatureUnder ice-cooling
11. additiontetra-n-propylammonium perruthenate (31 mg) was added
12. stirringthe mixture was stirred at room temperature for 3 hrs
13. customThe molecular sieves 4A was removed from the reaction solution by filtration
14. customThe solvent was evaporated under reduced pressure
15. customthe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=7/3→1/1)
16. dissolutionThe obtained colorless amorphous form was dissolved in ethanol (20 ml)
17. addition1,8-diazabicyclo[5.4.0]-7-undecene (0.84 ml) was added
18. temperatureThe mixture was heated
19. temperatureunder reflux for 12 hrs
20. customThe solvent was evaporated under reduced pressure
21. customthe residue was partitioned between ethyl acetate and 1N hydrochloric acid
22. washwashed with aqueous sodium hydrogen carbonate and brine and sodium sulfate
23. additionwas added
24. customto dry the mixture
25. customThe solvent was evaporated under reduced pressure
26. customthe obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=7/3→1/1)