Trifluoroacetic acid → Sodium 7-{2-[2-amino-1,3-thiazol-4-yl]-2-[1-(3-(3,4-dihydroxybenzoyl)carbazoyl)-1-methylethoxyimino]acetamido}-3-[(5-hydroxymethyl-2-methyl-s-triazolo[1,5-a]pyrimidin-7-yl)thiomethyl]-3-cephem-4-carboxylate

HRID 1032591Notes

Reaction equation

HRID 1032591 reaction equation
Cl.[NH2:2][C:3]1[S:4][CH:5]=[C:6]([C:8](=[N:12][O:13][C:14]([C:17](=[O:30])[NH:18][NH:19][C:20](=[O:29])[C:21]2[CH:26]=[CH:25][C:24]([OH:27])=[C:23]([OH:28])[CH:22]=2)([CH3:16])[CH3:15])[C:9](O)=[O:10])[N:7]=1.[NH2:31][CH:32]1[C:69](=[O:70])[N:34]2[C:35]([C:53]([O:55]C(C3C=CC=CC=3)C3C=CC=CC=3)=[O:54])=[C:36]([CH2:39][S:40][C:41]3[N:46]4[N:47]=[C:48]([CH3:50])[N:49]=[C:45]4[N:44]=[C:43]([CH2:51][OH:52])[CH:42]=3)[CH2:37][S:38][C@H:33]12.ON1C2C=CC=CC=2N=N1.C1CCC(N=C=NC2CCCCC2)CC1.FC(F)(F)C(O)=O.C1(OC)C=CC=CC=1.C(=O)([O-])O.[Na+:115]>CN(C=O)C.O.CCOCC>[NH2:2][C:3]1[S:4][CH:5]=[C:6]([C:8](=[N:12][O:13][C:14]([C:17](=[O:30])[NH:18][NH:19][C:20](=[O:29])[C:21]2[CH:26]=[CH:25][C:24]([OH:27])=[C:23]([OH:28])[CH:22]=2)([CH3:16])[CH3:15])[C:9]([NH:31][CH:32]2[C:69](=[O:70])[N:34]3[C:35]([C:53]([O-:55])=[O:54])=[C:36]([CH2:39][S:40][C:41]4[N:46]5[N:47]=[C:48]([CH3:50])[N:49]=[C:45]5[N:44]=[C:43]([CH2:51][OH:52])[CH:42]=4)[CH2:37][S:38][C@H:33]23)=[O:10])[N:7]=1.[Na+:115]

Participants

11

Reactant 7

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 884942522-(2-Amino-1,3-thiazol-4-yl)-2-{1-[3-(3,4-dihydroxybenzoyl)carbazoyl]-1-methylethoxyimino}acetic acid.hydrochlorideHCID 131716549Diphenylmethyl 7-amino-3-[(5-hydroxymethyl-2-methyl-s-triazolo[1,5-a]pyrimidin-7-yl)thiomethyl]-3-cephem-4-carboxylate

Product 1

HCID 131716550Sodium 7-{2-[2-amino-1,3-thiazol-4-yl]-2-[1-(3-(3,4-dihydroxybenzoyl)carbazoyl)-1-methylethoxyimino]acetamido}-3-[(5-hydroxymethyl-2-methyl-s-triazolo[1,5-a]pyrimidin-7-yl)thiomethyl]-3-cephem-4-carboxylate

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

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]-1-methylethoxyimino}acetic acid.hydrochloride, 5.17 g of diphenylmethyl 7-amino-3-[(5-hydroxymethyl-2-methyl-s-triazolo[1,5-a]pyrimidin-7-yl)thiomethyl]-3-cephem-4-carboxylate obtained in Example 37 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 30 minutes. After the reaction mixture was filtered, 15 ml of chloroform was added thereto and the mixture was added dropwise into 4 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 icecooled 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 3.75 g of the title compound.

Workup

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

Sources & evidence

ORD record
ord-8d5e03734b2345c894404968d02d460f
Source dataset
uspto-grants-1990_09
Patent number
US04958019

Reaction notes

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