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

HRID 580196Notes

Reaction equation

HRID 580196 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.[N:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=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+:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 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 1317155827-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[3-pyridinio-1-propen-1-yl]-3-cephem-4-carboxylateYield 8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture 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), pyridine (158 mg, 2 mmoles) in dimethylsulfoxide (DMSO) (1 ml) was stirred for 1 hour at room temperature. To the mixture was added ethyl acetate (20 ml) to precipitate a solid (620 mg), which was added to formic acid (6 ml) containing sodium bisulfite (60 mg). The mixture was stirred for 30 minutes at 40° C. and concentrated to dryness. The residue was dissolved in H2O (40 ml) and some insolubles were removed. The aqueous solution was charged on a column of reverse phase (PrepPAK-500/C18, 100 ml) eluting with H2O (300 ml) and 5% aqueous CH3OH (800 ml), and the eluate was monitored by uv (254 nm) and HPLC. The fractions (5% aqueous CH3OH) containing the desired product were combined, concentrated to a small volume and lyophilized to yield 40 mg (8%) of the title compound (I-1B), melting at >200° C. (dec.).

Workup

  1. customto precipitate a solid (620 mg), which
  2. additionwas added to formic acid (6 ml)
  3. additioncontaining sodium bisulfite (60 mg)
  4. stirringThe mixture was stirred for 30 minutes at 40° C.
  5. concentrationconcentrated to dryness
  6. dissolutionThe residue was dissolved in H2O (40 ml)
  7. customsome insolubles were removed
  8. additionThe aqueous solution was charged on a column of reverse phase (PrepPAK-500/C18, 100 ml)
  9. washeluting with H2O (300 ml) and 5% aqueous CH3OH (800 ml)
  10. additionThe fractions (5% aqueous CH3OH) containing the desired product
  11. concentrationconcentrated to a small volume

Sources & evidence

ORD record
ord-5eb95024453c49799e531b79888852a8
Source dataset
uspto-grants-1988_06
Patent number
US04751295

Reaction notes

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