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

HRID 615791Notes

Reaction equation

HRID 615791 reaction equation
[CH2:1]([O:4]/[N:5]=[C:6](/[C:37]1[N:38]=[C:39]([NH:42]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[S:40][CH:41]=1)\[C:7]([NH:9][CH:10]1[C:35](=[O:36])[N:12]2[C:13]([C:19]([O:21]C(C3C=CC=CC=3)C3C=CC=CC=3)=[O:20])=[C:14]([CH2:17]I)[CH2:15][S:16][C@H:11]12)=[O:8])[C:2]#[CH:3].[NH2:62][C:63]1[S:64][C:65]2[CH:70]=[CH:69][N:68]=[CH:67][C:66]=2[N:71]=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>CS(C)=O.C(OCC)(=O)C>[NH2:42][C:39]1[S:40][CH:41]=[C:37](/[C:6](=[N:5]/[O:4][CH2:1][C:2]#[CH:3])/[C:7]([NH:9][CH:10]2[C:35](=[O:36])[N:12]3[C:13]([C:19]([O-:21])=[O:20])=[C:14]([CH2:17][N+:68]4[CH:69]=[CH:70][C:65]5[S:64][C:63]([NH2:62])=[N:71][C:66]=5[CH:67]=4)[CH2:15][S:16][C@H:11]23)=[O:8])[N:38]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 14252938(1,3)Thiazolo(4,5-c)pyridin-2-amineHCID 88600779benzhydryl (6R)-3-(iodomethyl)-8-oxo-7-[[(2Z)-2-prop-2-ynoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 177706684(6R)-3-[(2-amino-[1,3]thiazolo[4,5-c]pyridin-5-ium-5-yl)methyl]-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-prop-2-ynoxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 81%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of diphenylmethyl 7-[(Z)-2-(propargyloxyimino)-2-(2-tritylaminothiazol-4-yl)acetamido]-3-iodomethyl-3-cephem-4-carboxylate [VIIf] (580 mg, 0.61 mmole), and 2-aminothiazolo[4,5-c]pyridine (94 mg, 0.62 mmole) in 2.5 ml of dry DMSO was stirred at room temperature for 30 minutes. The mixture was diluted with ethyl acetate (50 ml), and the resulting precipitate was collected by filtration and dissolved in CHCl3 --CH3OH (4:1, 50 ml). The solution was filtered and evaporated, and the residue was triturated with iso-propyl ether. The precipitate was collected by filtration to give 404 mg of crude quaternary salt [XIIIf], which was mixed with anisole (0.4 ml) and treated with 95% TFA (5 ml) under ice cooling. The solution was stirred at room temperature for an hour and then evaporated. The residue was triturated with iso-propyl ether and the resulting precipitate was collected by filtration to afford 282 mg of crude product If, which was purified on an HP-20 column (50 ml). Elution with water (150 ml), 30% aqueous CH3OH (200 ml) and 50% aqueous CH3OH (200 ml) gave 39 mg (5%) of If as pale yellow powder. Mp. 138°~150° C. (dec.). Estimated purity by HPLC: 45%.

Workup

  1. filtrationthe resulting precipitate was collected by filtration
  2. dissolutiondissolved in CHCl3 --CH3OH (4:1, 50 ml)
  3. filtrationThe solution was filtered
  4. customevaporated
  5. customthe residue was triturated with iso-propyl ether
  6. filtrationThe precipitate was collected by filtration
  7. customto give 404 mg of crude quaternary salt [XIIIf], which
  8. stirringThe solution was stirred at room temperature for an hour
  9. customevaporated
  10. customThe residue was triturated with iso-propyl ether
  11. filtrationthe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-8bc72ee809b54100b5bc56599d1abf8c
Source dataset
uspto-grants-1985_02
Patent number
US04500526

Reaction notes

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