反应详情

45 Milliliters of 20% hydrous pyridine was added to 2.71 g of 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]benzoic acid.hydrochloride, 3.0 g of 6-amidino-1-(2-carbamoylethyl)-2-naphthol.hydrochloride, 2.52 g of DCC and 124.6 mg of DMAP, followed by stirring for 2 hours under cooling with ice and 6 days under cooling with water. The precipitate was filtered and the filtrate was concentrated under reduced pressure. To the residue was added 15 ml of DMF, and a small amount of insoluble matter was filtered off. The filtrate was added dropwise to 400 ml of acetone, followed by stirring for 1 hour under cooling with ice and 24 hours under cooling with water. The supernatant was decanted, and to the residue was added 15 ml of methanol, followed by stirring for 1 hour under cooling with ice. The precipitate was collected by filtration to obtain a crude product. Then, the product was subjected to silica gel column chromatography using a mixed liquid of methyl ethyl ketone-water-acetic acid (80:15:5) as an eluent solvent, and the desired fractions were collected and the solvent was distilled off under reduced pressure. The residue was dissolved in 5 ml of DMF and 200 μl of concentrated hydrochloric acid, and the solution was added dropwise to 200 ml of acetone. After stirring for 1 hour under cooling with ice and then 24 hours under cooling with water, the precipitate was collected by filtration to obtain 495.4 mg of the desired product.

1. temperatureunder cooling with ice and 6 days
2. filtrationThe precipitate was filtered
3. concentrationthe filtrate was concentrated under reduced pressure
4. additionTo the residue was added 15 ml of DMF
5. filtrationa small amount of insoluble matter was filtered off
6. additionThe filtrate was added dropwise to 400 ml of acetone
7. stirringby stirring for 1 hour
8. temperatureunder cooling with ice and 24 hours
9. temperatureunder cooling with water
10. customThe supernatant was decanted
11. additionto the residue was added 15 ml of methanol
12. stirringby stirring for 1 hour
13. temperatureunder cooling with ice
14. filtrationThe precipitate was collected by filtration
15. customto obtain a crude product
16. customthe desired fractions were collected
17. distillationthe solvent was distilled off under reduced pressure
18. dissolutionThe residue was dissolved in 5 ml of DMF
19. addition200 μl of concentrated hydrochloric acid, and the solution was added dropwise to 200 ml of acetone
20. stirringAfter stirring for 1 hour
21. temperatureunder cooling with ice
22. temperature24 hours under cooling with water
23. filtrationthe precipitate was collected by filtration