Ethyl Acetate → 7beta-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-(3-carboxymethylamino-2-methyl-1-pyrazolio)methyl-3-cephem-4-carboxylate

HRID 1376420Notes

Reaction equation

HRID 1376420 reaction equation
Cl.Cl.Cl.[NH2:4][C@@H:5]1[C:28](=[O:29])[N:7]2[C:8]([C:25]([O-:27])=[O:26])=[C:9]([CH2:12][N+:13]3[N:14]([CH3:24])[C:15]([NH:18][CH2:19][C:20]([O:22]C)=[O:21])=[CH:16][CH:17]=3)[CH2:10][S:11][C@H:6]12.C[Si](C)(C)NC(=O)C.Cl.[NH2:39][C:40]1[S:44][N:43]=[C:42](/[C:45](=[N:49]/[O:50][CH3:51])/[C:46](Cl)=[O:47])[N:41]=1.C(OCC)(=O)C>O1CCCC1>[NH2:39][C:40]1[S:44][N:43]=[C:42]([C:45](=[N:49][O:50][CH3:51])[C:46]([NH:4][C@@H:5]2[C:28](=[O:29])[N:7]3[C:8]([C:25]([O-:27])=[O:26])=[C:9]([CH2:12][N+:13]4[N:14]([CH3:24])[C:15]([NH:18][CH2:19][C:20]([OH:22])=[O:21])=[CH:16][CH:17]=4)[CH2:10][S:11][C@H:6]23)=[O:47])[N:41]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25989Acetamide, N-(trimethylsilyl)-HCID 19930550(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl chloride;hydrochlorideHCID 1317201457beta-Amino-3-[2-methyl-3-methoxycarbonylmethylamino-1-pyrazolio]methyl-3-cephem-4-carboxylate trihydrochloride

Product 1

HCID 1317201437beta-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-(3-carboxymethylamino-2-methyl-1-pyrazolio)methyl-3-cephem-4-carboxylateYield 30.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7β-amino-3-[2-methyl-3-methoxycarbonylmethylamino-1-pyrazolio]methyl-3-cephem-4-carboxylate trihydrochloride (0.7 g) and N-(trimethylsilyl)acetamide (1.87 g) in tetrahydrofuran (14 ml) was added (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetyl chloride hydrochloride (0.37 g) under ice-cooling and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into ethyl acetate (140 ml) and the resultant powder was collected by filtration. The powder was dissolved in ice-water and adjusted to pH 13 with 1N aqueous sodium hydroxide. After stirring for 20 minutes under ice-cooling, the solution was adjusted to pH 2 with 3N hydrochloric acid and subjected to column chromatography on "Diaion HP-20" using 5% aqueous isopropyl alcohol as an eluent. Fractions containing the object compound were combined, evaporated in vacuo to remove isopropyl alcohol and lyophilized to give 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-(3-carboxymethylamino-2-methyl-1-pyrazolio)methyl-3-cephem-4-carboxylate (syn isomer) (0.24 g).

Workup

  1. temperaturecooling
  2. filtrationthe resultant powder was collected by filtration
  3. dissolutionThe powder was dissolved in ice-water
  4. stirringAfter stirring for 20 minutes under ice-
  5. temperaturecooling
  6. additionFractions containing the object compound
  7. customevaporated in vacuo
  8. customto remove isopropyl alcohol

Sources & evidence

ORD record
ord-3de1180b0a0a4da9b33af6ec73206707
Source dataset
uspto-grants-1997_09
Patent number
US05663163

Reaction notes

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