Nicotinamide → 7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[3-(3-carbamoylpyridinio)-1-propen-1-yl]-3-cephem-4-carboxylate

HRID 580199Notes

Reaction equation

HRID 580199 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4]([C:7](=[N:40][O:41][CH3:42])[C:8]([NH:10][CH:11]2[C:38](=[O:39])[N:13]3[C:14]([C:22]([O:24]C(C4C=CC=CC=4)C4C=CC=CC=4)=[O:23])=[C:15]([CH:18]=[CH:19][CH2:20]I)[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1.[C:43]([NH2:51])(=[O:50])[C:44]1[CH:49]=[CH:48][CH:47]=[N:46][CH:45]=1.C(OCC)(=O)C>CS(C)=O>[NH2:1][C:2]1[S:6][N:5]=[C:4]([C:7](=[N:40][O:41][CH3:42])[C:8]([NH:10][CH:11]2[C:38](=[O:39])[N:13]3[C:14]([C:22]([O-:24])=[O:23])=[C:15]([CH:18]=[CH:19][CH2:20][N+:46]4[CH:47]=[CH:48][CH:49]=[C:44]([C:43](=[O:50])[NH2:51])[CH:45]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1

Participants

5

Reactant 3

HCID 936NicotinamideHCID 8857Ethyl AcetateHCID 131715581Diphenylmethyl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-(3-iodo-1-propen-1-yl)-3-cephem-4-carboxylate

Product 1

HCID 1317155887-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[3-(3-carbamoylpyridinio)-1-propen-1-yl]-3-cephem-4-carboxylateYield 3.9%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of diphenylmethyl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-(3-iodo-1-propen-1-yl)-3-cephem-4-carboxylate (IX-1) (E, 716 mg, 1 mmole) in DMSO (2 ml) was added nicotinamide (244 mg, 2 mmoles), and the mixture was stirred at ambient temperature for 1.5 hours and poured into ethyl acetate (200 ml) with stirring. The resulting precipitate was collected by filtration. The quaternized salt (500 mg) was dissolved in HCOOH (5 ml) in the presence of sodium bisulfite (50 mg), and the mixture was heated at 40°-50° C. for 40 minutes, with stirring, and evaporated to dryness. The residue was dissolved in water (40 ml) and an insoluble solid was filtered off and washed with a small amount of water. The filtrate and wash were combined and chromatographed on a reverse phase column, PrepPAK-500/C18 (100 ml). After elution with water and 5%, 10% and 20% aqueous CH3OH, successively, the fractions containing the desired material were combined, concentrated in vacuo and freeze-dried to yield 21 mg (3.8%) of the title compound (I-1G) (E) as a yellow powder. Mp. >175° C. (dec.).

Workup

  1. stirringwith stirring
  2. filtrationThe resulting precipitate was collected by filtration
  3. dissolutionThe quaternized salt (500 mg) was dissolved in HCOOH (5 ml) in the presence of sodium bisulfite (50 mg)
  4. temperaturethe mixture was heated at 40°-50° C. for 40 minutes
  5. stirringwith stirring
  6. customevaporated to dryness
  7. dissolutionThe residue was dissolved in water (40 ml)
  8. filtrationan insoluble solid was filtered off
  9. washwashed with a small amount of water
  10. washThe filtrate and wash
  11. customchromatographed on a reverse phase column
  12. washAfter elution with water and 5%, 10% and 20% aqueous CH3OH
  13. additionsuccessively, the fractions containing the desired material
  14. concentrationconcentrated in vacuo
  15. customfreeze-dried

Sources & evidence

ORD record
ord-3cb73090aa8a46b0806ab0a41ba37d44
Source dataset
uspto-grants-1988_06
Patent number
US04751295

Reaction notes

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