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

HRID 580195Notes

Reaction equation

HRID 580195 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.[CH3:43][N:44]1[CH2:48][CH2:47][CH2:46][CH2:45]1>C(OCC)(=O)C.C(OC(C)C)(C)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+:44]4([CH3:43])[CH2:48][CH2:47][CH2:46][CH2:45]4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1

Participants

5

Reactant 2

HCID 84541-MethylpyrrolidineHCID 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 1317155797-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[3-(1-methylpyrrolidinio)-1-propen-1-yl]-3-cephem-4-carboxylateYield 12.2%

Reagents, catalysts & solvents 2

HCID 7914Diisopropyl EtherSolventHCID 8857Ethyl AcetateSolvent2×

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) (Z/E=2/1, 150 mg, 0.21 mmole) in ethyl acetate (2 ml) was added a solution of 1-methylpyrrolidine (36 mg, 0.42 mmole) in ethyl acetate (1 ml) in one portion with stirring. The mixture was stirred for 15 minutes and diluted with isopropyl ether (10 ml) to form a precipitate, which was collected by filtration. A mixture of the solid (130 mg), formic acid (1 ml) and concentrated HCl (0.1 ml) was stirred at room temperature. After 1 hour, the reaction mixture was concentrated under reduced pressure, diluted with water (20 ml) and filtered. The aqueous solution was passed through a reverse phase column (the packing of PrepPAK-500/C18 cartridge, 100 ml), eluting with water and 10% CH3OH. The desired fractions were collected, and concentrated in vacuo to a small volume and freeze-dried to give 13 mg (12%) of the title compound (I-1A) (Z/E=1/1), melting at >280° C. (dec.).

Workup

  1. stirringThe mixture was stirred for 15 minutes
  2. customto form a precipitate, which
  3. filtrationwas collected by filtration
  4. additionA mixture of the solid (130 mg), formic acid (1 ml) and concentrated HCl (0.1 ml)
  5. stirringwas stirred at room temperature
  6. concentrationthe reaction mixture was concentrated under reduced pressure
  7. additiondiluted with water (20 ml)
  8. filtrationfiltered
  9. washeluting with water and 10% CH3OH
  10. customThe desired fractions were collected
  11. concentrationconcentrated in vacuo to a small volume
  12. customfreeze-dried

Sources & evidence

ORD record
ord-dd4a66f088fc462aaf4551f5dd8bb551
Source dataset
uspto-grants-1988_06
Patent number
US04751295

Reaction notes

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