(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-8-oxo-3-(pyrazin-2-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid → (6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(pyrazin-2-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

HRID 992704Notes

Reaction equation

HRID 992704 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:31]/[O:32]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)/[C:8]([NH:10][C@@H:11]2[C:29](=[O:30])[N:13]3[C:14]([C:26]([OH:28])=[O:27])=[C:15]([S:18][CH2:19][C:20]4[CH:25]=[N:24][CH:23]=[CH:22][N:21]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1>C(O)=O>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:31]/[OH:32])/[C:8]([NH:10][C@@H:11]2[C:29](=[O:30])[N:13]3[C:14]([C:26]([OH:28])=[O:27])=[C:15]([S:18][CH2:19][C:20]4[CH:25]=[N:24][CH:23]=[CH:22][N:21]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1

Participants

3

Reactant 1

HCID 88179745(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-trityloxyiminoacetyl]amino]-8-oxo-3-(pyrazin-2-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Product 1

HCID 88179048(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(pyrazin-2-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acidYield 13%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Procedure

A solution of 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(trityloxyimino)acetamido]-3-[(pyrazin-2-yl)methylthio]-3-cephem-4-carboxylic acid (1.5 g, 2.04 m mol) in 90% formic acid aqueous solution was stirred at room temperature for 2 hours. Insoluble material in the reaction mixture was filtered off. The filtrate was adjusted to pH 3 and washed with ethyl acetate. The aqueous solution was chromatographed on HP-20 and eluted with 5-14% isopropanol aqueous solution. The eluent was lyophilized to give crude product (275 mg). The crude product was purified with preparative HPLC to give 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-(hydroxyimino)acetamido]-3-[(pyrazin-2-yl)methylthio]-3-cephem-4-carboxylic acid (131 mg, 0.265 m mol).

Workup

  1. filtrationInsoluble material in the reaction mixture was filtered off
  2. washwashed with ethyl acetate
  3. customThe aqueous solution was chromatographed on HP-20
  4. washeluted with 5-14% isopropanol aqueous solution
  5. customto give crude product (275 mg)
  6. customThe crude product was purified with preparative HPLC

Sources & evidence

ORD record
ord-b6dbd1e32d7a4e729cc4b83df18aa082
Source dataset
uspto-grants-2002_10
Patent number
US06468995B1

Reaction notes

Loading…