Hydrochloric Acid → (6R,7R)-3-[[5-amino-4-(aminomethyl)-1-(2-hydroxyethyl)pyrazol-2-ium-2-yl]methyl]-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 349537Notes

Reaction equation

HRID 349537 reaction equation
[NH2:1][C:2]1[S:6][N:5]=[C:4](/[C:7](=[N:37]/[O:38][C:39]([C:42]([OH:44])=[O:43])([CH3:41])[CH3:40])/[C:8]([NH:10][C@@H:11]2[C:35](=[O:36])[N:13]3[C:14]([C:32]([O-:34])=[O:33])=[C:15]([CH2:18][N+:19]4[N:20]([CH2:29][CH2:30][OH:31])[C:21]([NH2:28])=[C:22]([CH2:24][NH:25]C=O)[CH:23]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1.Cl.C(OCC)(=O)C>CO>[NH2:1][C:2]1[S:6][N:5]=[C:4](/[C:7](=[N:37]/[O:38][C:39]([C:42]([OH:44])=[O:43])([CH3:41])[CH3:40])/[C:8]([NH:10][C@@H:11]2[C:35](=[O:36])[N:13]3[C:14]([C:32]([O-:34])=[O:33])=[C:15]([CH2:18][N+:19]4[N:20]([CH2:29][CH2:30][OH:31])[C:21]([NH2:28])=[C:22]([CH2:24][NH2:25])[CH:23]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:3]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 141600993(6R,7R)-3-[[5-amino-4-(formamidomethyl)-1-(2-hydroxyethyl)pyrazol-2-ium-2-yl]methyl]-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 141600997(6R,7R)-3-[[5-amino-4-(aminomethyl)-1-(2-hydroxyethyl)pyrazol-2-ium-2-yl]methyl]-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 18.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[3-amino-4-formamidomethyl-2-(2-hydroxyethyl)-1-pyrazolio]methyl-3-cephem-4-carboxylate (97 mg) in methanol (1 ml) was added concentrated hydrochloric acid (0.1 ml) at room temperature. The mixture was stirred at room temperature for 4.5 hours and poured into ethyl acetate. The resulting precipitate was collected by filtration and dried in vacuo. The obtained powder was dissolved in a phosphate buffer (pH 7), and the solution was adjusted to about pH 6 with saturated aqueous sodium hydrogencarbonate solution. The solution containing the objective compound was purified by preparative HPLC utilizing ODS column. The eluate containing the desired product was concentrated in vacuo. The concentrate was adjusted to about pH 2 with concentrated hydrochloric acid and chromatographed on Diaion® HP-20 (Mitsubishi Chemical Corporation) eluting with 20% aqueous 2-propanol. The eluate was concentrated in vacuo and lyophilized to give 7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-[3-amino-4-aminomethyl-2-(2-hydroxyethyl)-1-pyrazolio]methyl-3-cephem-4-carboxylate (17.5 mg).

Workup

  1. filtrationThe resulting precipitate was collected by filtration
  2. customdried in vacuo
  3. dissolutionThe obtained powder was dissolved in a phosphate buffer (pH 7)
  4. additionThe solution containing the objective compound
  5. customwas purified by preparative HPLC utilizing ODS column
  6. additionThe eluate containing the desired product
  7. concentrationwas concentrated in vacuo
  8. customchromatographed on Diaion®
  9. wash(Mitsubishi Chemical Corporation) eluting with 20% aqueous 2-propanol
  10. concentrationThe eluate was concentrated in vacuo

Sources & evidence

ORD record
ord-634ce5b286ba410abaa26490ab4468b7
Source dataset
uspto-grants-2007_02
Patent number
US07179801B2

Reaction notes

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