反应详情

15 Milliliters of anhydrous pyridine was added to 1.0 g of 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]-benzoic acid.hydrochloride, 1.38 g of 6-amidino-1-dimethylcarbamoylmethoxycarbonyl-2-naphthol.hydrochloride, 1.28 g of DCC and 50.5 mg of DMAP, followed by stirring for 2 hours under cooling with ice and then 48 hours at room temperature. Then, the precipitate was collected by filtration, and dissolved by adding thereto 50 ml of warm DMF, 0.5 ml of 1N-hydrochloric acid and 2 ml of water, followed by stirring for 1 hour under cooling with ice. The precipitate was filtered and the filtrate was concentrated under reduced pressure. To the residue was added 15 ml of DMF, and the solution was added dropwise to a mixed liquid of 150 ml of acetone and 50 ml of ether, followed by stirring for 1 hour under cooling with ice. Then, the precipitate was collected by filtration to obtain a crude product. Then, the product was subjected to silica gel column chromatography using methyl ethyl ketone-water-acetic acid (80:15:5) as an eluent, and the desired fractions were collected and the solvent was distilled off under reduced pressure. To the residue were added 5 ml of DMF and 0.7 ml of concentrated hydrochloric acid, and the solution was added dropwise to 150 ml of acetone, followed by stirring for 24 hours under cooling with ice. Then, the precipitate was collected by filtration to obtain 447.8 mg of the desired product.

1. temperatureunder cooling with ice
2. custom48 hours
3. customat room temperature
4. filtrationThen, the precipitate was collected by filtration
5. dissolutiondissolved
6. additionby adding
7. stirringby stirring for 1 hour
8. temperatureunder cooling with ice
9. filtrationThe precipitate was filtered
10. concentrationthe filtrate was concentrated under reduced pressure
11. additionTo the residue was added 15 ml of DMF
12. additionthe solution was added dropwise to a mixed liquid of 150 ml of acetone and 50 ml of ether
13. stirringby stirring for 1 hour
14. temperatureunder cooling with ice
15. filtrationThen, the precipitate was collected by filtration
16. customto obtain a crude product
17. customthe desired fractions were collected
18. distillationthe solvent was distilled off under reduced pressure
19. additionTo the residue were added 5 ml of DMF and 0.7 ml of concentrated hydrochloric acid
20. additionthe solution was added dropwise to 150 ml of acetone
21. stirringby stirring for 24 hours
22. temperatureunder cooling with ice
23. filtrationThen, the precipitate was collected by filtration