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

HRID 615802Notes

Reaction equation

HRID 615802 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].[N:60]1([C:65]([NH:67][C:68]2[S:69][C:70]3[CH:75]=[CH:74][N:73]=[CH:72][C:71]=3[N:76]=2)=[O:66])[CH2:64][CH2:63][CH2:62][CH2:61]1.C(O)(C(F)(F)F)=O>CS(C)=O.C1(OC)C=CC=CC=1>[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+:73]4[CH:74]=[CH:75][C:70]5[S:69][C:68]([NH:67][C:65]([N:60]6[CH2:64][CH2:63][CH2:62][CH2:61]6)=[O:66])=[N:76][C:71]=5[CH:72]=4)[CH2:13][S:14][C@H:9]23)=[O:6])[N:36]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acidHCID 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 15593550HCID 15593550, compound

Product 1

HCID 177720691(6R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-[[2-(pyrrolidine-1-carbonylamino)-[1,3]thiazolo[4,5-c]pyridin-5-ium-5-yl]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 51.3%

Reagents, catalysts & solvents 2

HCID 7519AnisoleCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

A solution 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-(pyrrolidin-1-yl-carbonylamino)thiazolo[4,5-c]pyridine (124 mg, 0.5 mmoles) in 2 ml DMSO was allowed to stand at room temperature for 1.5 hours and then triturated with ether to give 606 mg of crude quaternary salt as a powder. The powder was added to a mixture of 5 ml of TFA and 3 drops of anisole and stirred 30 minutes at room temperature. The mixture then was evaporated under reduced pressure and triturated with ether to give 375 mg of crude It, which was purified on a column of HP-20 resin (40 ml) using 50% aqueous CH3OH as an eluant to give 165 mg (51%) of the desired product It. Mp. 184°~198° C. (dec.). Estimated purity by HPLC: 65%.

Workup

  1. customtriturated with ether
  2. customto give 606 mg of crude quaternary salt as a powder
  3. customThe mixture then was evaporated under reduced pressure
  4. customtriturated with ether
  5. customto give 375 mg of crude It, which
  6. customwas purified on a column of HP-20 resin (40 ml)

Sources & evidence

ORD record
ord-58c0249110564b59809f3587b22682ad
Source dataset
uspto-grants-1985_02
Patent number
US04500526

Reaction notes

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