Dimethylformamide → 7-[2-(2-Formamidothiazol-4-yl)-2-cyanomethoxyiminoacetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid

HRID 255755Notes

Reaction equation

HRID 255755 reaction equation
P(Cl)(Cl)(Cl)=O.CN(C)C=O.[CH:11]([NH:13][C:14]1[S:15][CH:16]=[C:17]([C:19](=[N:23][O:24][CH2:25][C:26](=O)[NH2:27])[C:20]([OH:22])=O)[N:18]=1)=[O:12].[NH2:29][CH:30]1[C:47](=[O:48])[N:32]2[C:33]([C:44]([OH:46])=[O:45])=[C:34]([CH2:37][S:38][C:39]3[S:40][CH:41]=[N:42][N:43]=3)[CH2:35][S:36][C@H:31]12>CC(C)=O.C(N(CC)CC)C.O1CCCC1>[CH:11]([NH:13][C:14]1[S:15][CH:16]=[C:17]([C:19](=[N:23][O:24][CH2:25][C:26]#[N:27])[C:20]([NH:29][CH:30]2[C:47](=[O:48])[N:32]3[C:33]([C:44]([OH:46])=[O:45])=[C:34]([CH2:37][S:38][C:39]4[S:40][CH:41]=[N:42][N:43]=4)[CH2:35][S:36][C@H:31]23)=[O:22])[N:18]=1)=[O:12]

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 24813Phosphorus oxychlorideHCID 128891877-Amino-3-(1,3,4-thiadiazol-2-ylthiomethyl)-3cephem-4-carboxylic acidHCID 538052302-(2-Formamidothiazol-4-yl)-2-carbamoylmethoxyiminoacetic acid

Product 1

HCID 1317152817-[2-(2-Formamidothiazol-4-yl)-2-cyanomethoxyiminoacetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acidYield 34.8%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

Phosphoryl chloride (0.96 g.), N,N-dimethylformamide (0.459 g.), tetrahydrofuran (12 ml.) and 2-(2-formamidothiazol-4-yl)-2-carbamoylmethoxyiminoacetic acid (syn isomer, 1.2 g.) were treated in a similar manner to that of Example 1-(1) to give an activated acid solution. After a suspension of 7-amino-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (1.75 g.) in 50% aqueous acetone (16 ml.) was adjusted to pH 7 to 8.5 with triethylamine, the activated acid solution was added to the stirred solution at -5° to 0° C. while keeping at pH 6.5 to 7.5 and stirred at the same temperature for 30 minutes. After removing the solvent from the resultant solution in vacuo, ethyl acetate was added to the residue. The solution was adjusted to pH 1.5 with 10% hydrochloric acid and the insoluble substance was filtered off. The filtrate was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated in vacuo. The residue was pulverized with diethyl ether to give 7-[2-(2-formamidothiazol-4-yl)-2-cyanomethoxyiminoacetamido]-3-(1,3,4-thiadiazol-2-yl)thiomethyl-3-cephem-4-carboxylic acid (syn isomer, 0.87 g.).

Workup

  1. customto give an activated acid solution
  2. additionthe activated acid solution was added to the stirred solution at -5° to 0° C.
  3. customAfter removing the solvent from the resultant solution in vacuo, ethyl acetate
  4. additionwas added to the residue
  5. filtrationthe insoluble substance was filtered off
  6. extractionThe filtrate was extracted with ethyl acetate
  7. washThe extract was washed with a saturated aqueous solution of sodium chloride
  8. dry with materialdried over magnesium sulfate
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cbc6549da07743cea36d49f9ada22982
Source dataset
uspto-grants-1987_10
Patent number
US04698337

Reaction notes

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