HCID 178451388, compound → sodium (6R,7R)-3-[[3-(2-amino-2-iminoethyl)sulfanyl-4-cyano-1,2-thiazol-5-yl]sulfanylmethyl]-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(carboxymethoxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1073823Notes

Reaction equation

HRID 1073823 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:25]/[O:26][CH2:27][C:28]([O:30]C(C)(C)C)=[O:29])/[C:8]([NH:10][C@@H:11]2[C:23](=[O:24])[N:13]3[C:14]([C:20]([O-:22])=[O:21])=[C:15]([CH2:18]O)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.[Na+:35].[C:36]([CH2:39][S:40][C:41]1[C:45]([C:46]#[N:47])=[C:44]([SH:48])[S:43][N:42]=1)(=[NH:38])[NH2:37]>CN(C=O)C>[C:36]([CH2:39][S:40][C:41]1[C:45]([C:46]#[N:47])=[C:44]([S:48][CH2:18][C:15]2[CH2:16][S:17][C@@H:12]3[C@H:11]([NH:10][C:8](=[O:9])/[C:7](/[C:5]4[N:6]=[C:2]([NH2:1])[S:3][CH:4]=4)=[N:25]\[O:26][CH2:27][C:28]([OH:30])=[O:29])[C:23](=[O:24])[N:13]3[C:14]=2[C:20]([O-:22])=[O:21])[S:43][N:42]=1)(=[NH:37])[NH2:38].[Na+:35]

Participants

4

Reactant 2

HCID 178451388HCID 178451388, compoundHCID 178510535HCID 178510535, compound

Product 1

HCID 23676290sodium (6R,7R)-3-[[3-(2-amino-2-iminoethyl)sulfanyl-4-cyano-1,2-thiazol-5-yl]sulfanylmethyl]-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(carboxymethoxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 50.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of sodium 7β-[2-(2-aminothiazol-4-yl) -(Z)-2-(tert-butoxycarbonylmethoxyimino)acetamido]-3-hydroxymethyl-3-cephem-4-carboxylate (554 mg) and 3-amidinomethylthio-4-cyano-5-mercaptoisothiazole (345 mg) in 7 ml of DMF was added 1.2 g of ethyl o-phenylenephosphate under stirring at -20° C. After stirring under ice-cooling for 2 hours, the reaction mixture was subjected to a column chromatography on silica gel (150 g), being washed with acetonitrile and eluted with acetonitrile/water (6:1). The eluate was concentrated. The resultant precipitate was collected by filtration and dissolved in 40 ml of trifluoroacetic acid under ice-cooling. The mixture was stirred at room temperature for an hour and distilled to remove the solvent. The residue was dissolved in a mixture of water and THF and then adjusted to pH 6 with an aqueous sodium hydrogencarbonate solution. The solution was washed with ethyl acetate, concentrated under reduced pressure and subjected to a column chromatography on XAD-II (150 ml), being washed with water and eluted with 20% aqueous ethanol. The eluate was concentrated under reduced pressure and lyophilized to give 363 mg of the title compound as a pale yellow powder.

Workup

  1. stirringAfter stirring under ice-
  2. temperaturecooling for 2 hours
  3. washbeing washed with acetonitrile
  4. washeluted with acetonitrile/water (6:1)
  5. concentrationThe eluate was concentrated
  6. filtrationThe resultant precipitate was collected by filtration
  7. dissolutiondissolved in 40 ml of trifluoroacetic acid under ice-
  8. temperaturecooling
  9. stirringThe mixture was stirred at room temperature for an hour
  10. distillationdistilled
  11. customto remove the solvent
  12. dissolutionThe residue was dissolved in a mixture of water and THF
  13. washThe solution was washed with ethyl acetate
  14. concentrationconcentrated under reduced pressure
  15. washbeing washed with water
  16. washeluted with 20% aqueous ethanol
  17. concentrationThe eluate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-a363fa09345f4701b2a4ef77e90b612f
Source dataset
uspto-grants-1990_11
Patent number
US04971963

Reaction notes

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