反应详情

In 30 ml of DMF were dissolved 3.22 g of 2-(2-amino-1,3-thiazol-4-yl)-2-{1-[3-(3,4-dihydroxybenzoyl)carbazoyl]-1methylethoxyimino}acetic acid.hydrochloride, 5.32 g of diphenylmethyl 7-amino-3-[(2,5-bis(hydroxymethyl)-s-triazolo[1,5-a]pyrimidin-7-yl)thiomethyl]-3-cephem-4-carboxylate obtained in Example 41 and 1.38 g of 1-hydroxybenzotriazole and ice-cooled. Then, 1.86 g of DCC was added thereto and the mixture was stirred for 15 minutes under ice-cooling, and further stirred at room temperature for one hour. After the reaction mixture was filtered, 15 ml of chloroform was added thereto and the mixture was added dropwise into 2 liters of ether. Precipitates were collected by filtration, washed with ether and then dried. Powder obtained was purified through silica gel column chromatography to obtain powder. A mixed solution of 30 ml of trifluoroacetic acid and 8 ml of anisole was ice-cooled and the powder previously obtained was added thereto, and the mixture was stirred for 30 minutes and added dropwise into 400 ml of ether. Precipitates were collected by filtration, washed with ether and then dried to obtain powder. The powder was suspended in 200 ml of water and dissolved at pH 7 by adding a 5% sodium hydrogencarbonate solution. After the resulting solution was adsorbed to 200 ml of HP 20 column filled with water, it was washed with water. Subsequently, the mixture was eluted with a 50% methanol - water. After evaporation of methanol, the residue was freeze-dried to obtain 4.16 g of the title compound. 1H NMR (d6 -DMSO) δ: 1.60 (s, 6H), 3.86 (broad s, 2H), 4.60 (broad s, 2H), 4.78 (s, 4H), 5.40 (d, J=5Hz, 1H), 5.87 to 6.27 (m, 1H), 6.94 to 7.72 (m, 5H).

1. temperaturecooled
2. temperaturecooling
3. stirringfurther stirred at room temperature for one hour
4. filtrationAfter the reaction mixture was filtered
5. addition15 ml of chloroform was added
6. additionthe mixture was added dropwise into 2 liters of ether
7. customPrecipitates
8. filtrationwere collected by filtration
9. washwashed with ether
10. customdried
11. customPowder obtained
12. customwas purified through silica gel column chromatography
13. customto obtain powder
14. temperaturecooled
15. customthe powder previously obtained
16. additionwas added
17. stirringthe mixture was stirred for 30 minutes
18. customPrecipitates
19. filtrationwere collected by filtration
20. washwashed with ether
21. customdried
22. customto obtain powder
23. dissolutiondissolved at pH 7
24. washwas washed with water
25. washSubsequently, the mixture was eluted with a 50% methanol - water
26. customAfter evaporation of methanol
27. customthe residue was freeze-dried