benzhydryl (6R)-3-(iodomethyl)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate → HCID 178502757, compound

HRID 2164986Notes

Reaction equation

HRID 2164986 reaction equation
[CH3:1][O:2]/[N:3]=[C:4](/[C:35]1[N:36]=[C:37]([NH:40]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[S:38][CH:39]=1)\[C:5]([NH:7][CH:8]1[C:33](=[O:34])[N:10]2[C:11]([C:17]([O:19]C(C3C=CC=CC=3)C3C=CC=CC=3)=[O:18])=[C:12]([CH2:15]I)[CH2:13][S:14][C@H:9]12)=[O:6].C(OC([NH:67][CH2:68][CH2:69][C:70]1[S:74][CH:73]=[N:72][C:71]=1[CH3:75])=O)(C)(C)C>C(Cl)Cl.CS(C)=O.C(OCC)(=O)C>[NH2:40][C:37]1[S:38][CH:39]=[C:35](/[C:4](=[N:3]/[O:2][CH3:1])/[C:5]([NH:7][CH:8]2[C:33](=[O:34])[N:10]3[C:11]([C:17]([O-:19])=[O:18])=[C:12]([CH2:15][C:73]4[S:74][C:70]([CH2:69][CH2:68][NH2:67])=[C:71]([CH3:75])[NH+:72]=4)[CH2:13][S:14][C@H:9]23)=[O:6])[N:36]=1

Participants

6

Reactant 2

HCID 13239634benzhydryl (6R)-3-(iodomethyl)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 20403509HCID 20403509, compound

Product 1

HCID 178502757HCID 178502757, compoundYield 14%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of diphenylmethyl 7-[(Z)-2-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-iodomethyl-3-cephem-4-carboxylate (VII-1) 468 mg, 0.5 mmole) and 5-(2-t-butoxycarbonylaminoethyl)-4-methylthiazole (242 mg, 1 mmole) [prepared by t-butoxycarbonylation of 5-(2-aminoethyl)-4-methylthiazole; see K. M. Muraveva and M. N. Shchukina, Zh. Obshch. Khim., 33, 3723 (1963); CA, 60, 8012a (1964)] in a mixture of methylene chloride (2 mL) and DMSO (0.5 mL) was stirred for 6 hours at room temperature and diluted with ethyl acetate (100 mL). The mixture was washed with water and evaporated under reduced pressure. The residue was triturated with ether and 400 mg of the quaternary salt was collected by filtration and treated with TFA (5 mL) for 2 hours at room temperature. After removal of TFA under reduced pressure below 20° C., the mixtrue was triturated with ether and 310 mg of the TFA salt of the crude product was collected by filtration. The TFA salt was dissolved in a small amount of aqueous NaHCO3 and chromatographed on a column of HP-20 (1.8×20 cm) by eluting with water. The fractions containing the title compound were combined, concentrated under reduced pressure and freeze-dried to give 36 mg (yield 14%) of the title product [Ij]. Estimated purity 50% (by HPLC).

Workup

  1. washThe mixture was washed with water
  2. customevaporated under reduced pressure
  3. customThe residue was triturated with ether and 400 mg of the quaternary salt
  4. filtrationwas collected by filtration
  5. additiontreated with TFA (5 mL) for 2 hours at room temperature
  6. customAfter removal of TFA under reduced pressure below 20° C.
  7. customthe mixtrue was triturated with ether and 310 mg of the TFA salt of the crude product
  8. filtrationwas collected by filtration
  9. dissolutionThe TFA salt was dissolved in a small amount of aqueous NaHCO3
  10. customchromatographed on a column of HP-20 (1.8×20 cm)
  11. washby eluting with water
  12. additionThe fractions containing the title compound
  13. concentrationconcentrated under reduced pressure
  14. customfreeze-dried

Sources & evidence

ORD record
ord-7e7364966ad941d7b76ac530b7f47e9f
Source dataset
uspto-grants-1985_03
Patent number
US04507487

Reaction notes

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