Trifluoroacetic acid → (6R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[[2-(dimethylamino)-[1,3]thiazolo[4,5-c]pyridin-5-ium-5-yl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 615803Notes

Reaction equation

HRID 615803 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].[CH3:60][N:61]([CH3:71])[C:62]1[S:63][C:64]2[CH:69]=[CH:68][N:67]=[CH:66][C:65]=2[N:70]=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>CS(C)=O.CCOCC.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][N+:67]4[CH:68]=[CH:69][C:64]5[S:63][C:62]([N:61]([CH3:71])[CH3:60])=[N:70][C:65]=5[CH:66]=4)[CH2:13][S:14][C@H:9]23)=[O:6])[N:36]=1

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 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 15593551Thiazolo[4,5-c]pyridin-2-amine, N,N-dimethyl-

Product 1

HCID 177744000(6R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[[2-(dimethylamino)-[1,3]thiazolo[4,5-c]pyridin-5-ium-5-yl]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 31.3%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of diphenylmethyl 7-[(Z)-2-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-iodomethyl-3-cephem-4-carboxylate [VIIa] (466 mg, 0.5 mmole) and 2-dimethylaminothiazolo[4,5-c]pyridine (90 mg, 0.5 mmole) in dry DMSO (1 ml) was stirred at room temperature for 40 minutes, and diluted with a mixture of ether (20 ml) and ethyl acetate (50 ml). The precipitate was collected by filtration to obtain 517 mg of the crude quaternary salt. The salt was mixed with 0.3 ml of anisole and was treated with 95% TFA under ice cooling. The solution was stirred for an hour at room temperature and evaporated. The residue was triturated with iso-propyl ether and the resulting precipitate was collected by filtration to give 367 mg of the crude title compound as a yellow powder. The crude product was purified by chromatography (HP-20 column 90 ml), eluted with water (200 ml), 30% CH3OH (240 ml), and 50% CH3OH (450 ml). The desired fractions were combined, concentrated and lyophilized to give 90 mg of yellow powder, which was further purified by column chromatography by using the packing of PrepPAK/C18 cartridge (50 ml). The column was eluted with water (100 ml) and 30% CH3OH (200 ml). The desired fractions were concentrated and lyophilized to obtain 40 mg of Iu as pale yellow powder (14% yield). Mp. 119°~123° C. (dec.). Estimated purity by HPLC: 65%.

Workup

  1. filtrationThe precipitate was collected by filtration
  2. customto obtain 517 mg of the crude quaternary salt
  3. stirringThe solution was stirred for an hour at room temperature
  4. customevaporated
  5. customThe residue was triturated with iso-propyl ether
  6. filtrationthe resulting precipitate was collected by filtration
  7. customto give 367 mg of the crude title compound as a yellow powder
  8. customThe crude product was purified by chromatography (HP-20 column 90 ml)
  9. washeluted with water (200 ml), 30% CH3OH (240 ml), and 50% CH3OH (450 ml)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-e2814fa1be724a4ebcd0bd62764074e8
Source dataset
uspto-grants-1985_02
Patent number
US04500526

Reaction notes

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