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

HRID 580202

Reaction equation

HRID 580202 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][N:47]=[CH:46][CH:45]=1.C(Cl)(Cl)Cl.CO>CS(C)=O.C(OCC)(=O)C>[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+:47]4[CH:48]=[CH:49][C:44]([C:43](=[O:50])[NH2:51])=[CH:45][CH:46]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 6212ChloroformHCID 15074IsonicotinamideHCID 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 1317155907-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[3-(4-carbamoylpyridinio)-1-propenyl]-3-cephem-4-carboxylateYield 8.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

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 isomer, 4.1 g, 5.7 mmoles) and isonicotinamide (1.4 g, 11 mmoles) in dry DMSO (6 ml) was stirred for 2 hours at room temperature while monitoring by TLC (silica gel plate, CHCl3 :CH3OH=3:1). The reaction mixture was diluted with ethyl acetate (100 ml) to separate a yellow gum, which was treated with formic acid (40 ml) and sodium bisulfite (390 mg) at 45° C. for 30 minutes. The resulting solution was concentrated to dryness. The residue was dissolved in H2O (100 ml) and insolubles were removed by filtration. The combined filtrate and water wash was applied to the top of a column containing reverse phase packing (PrepPAK-500/C18, 120 ml). The column was eluted with H2O. The eluate was collected in 300 ml fractions and monitored by uv (254 nm) and HPLC (Lichrosorb RP-18, 4×300 mm, 0.01M ammonium phosphate buffer, pH 7.2 containing 20% CH3OH). Fraction Nos. 4 and 5 were combined and concentrated to a small volume. Lyophilization gave 250 mg (8.1%) of the title compound I-1H, melting at >180° C. (dec.).

Workup

  1. customto separate a yellow gum, which
  2. additionwas treated with formic acid (40 ml) and sodium bisulfite (390 mg) at 45° C. for 30 minutes
  3. concentrationThe resulting solution was concentrated to dryness
  4. dissolutionThe residue was dissolved in H2O (100 ml)
  5. custominsolubles were removed by filtration
  6. washThe combined filtrate and water wash
  7. additioncontaining reverse phase packing (PrepPAK-500/C18, 120 ml)
  8. washThe column was eluted with H2O
  9. customThe eluate was collected in 300 ml fractions
  10. additionmonitored by uv (254 nm) and HPLC (Lichrosorb RP-18, 4×300 mm, 0.01M ammonium phosphate buffer, pH 7.2 containing 20% CH3OH)
  11. concentrationconcentrated to a small volume

Sources & evidence

ORD record
ord-4a70d20d63d4452fbb7048fca6035b54
Source dataset
uspto-grants-1988_06
Patent number
US04751295

Linked notes

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