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

HRID 615789Notes

Reaction equation

HRID 615789 reaction equation
I[CH2:2][C:3]1[CH2:4][S:5][C@@H:6]2[CH:26]([NH:27][C:28](=[O:58])/[C:29](=[N:55]\[O:56][CH3:57])/[C:30]3[N:31]=[C:32]([NH:35]C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[S:33][CH:34]=3)[C:25](=[O:59])[N:7]2[C:8]=1[C:9]([O:11]C(C1C=CC=CC=1)C1C=CC=CC=1)=[O:10].[S:60]1[C:68]2[CH:67]=[CH:66][N:65]=[CH:64][C:63]=2[N:62]=[CH:61]1>CS(C)=O.C(OCC)(=O)C>[NH2:35][C:32]1[S:33][CH:34]=[C:30](/[C:29](=[N:55]/[O:56][CH3:57])/[C:28]([NH:27][CH:26]2[C:25](=[O:59])[N:7]3[C:8]([C:9]([O-:11])=[O:10])=[C:3]([CH2:2][N+:65]4[CH:66]=[CH:67][C:68]5[S:60][CH:61]=[N:62][C:63]=5[CH:64]=4)[CH2:4][S:5][C@H:6]23)=[O:58])[N:31]=1

Participants

5

Reactant 2

HCID 585837Thiazolo[4,5-c]pyridineHCID 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-carboxylate

Product 1

HCID 141546260(6R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-3-([1,3]thiazolo[4,5-c]pyridin-5-ium-5-ylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 22%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of benzhydryl 3-iodomethyl-7-[(Z)-2-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylate [VIIa] (1.50 g, 1.61 mmoles) and thiazolo[4,5-c]-pyridine (300 mg, 2.20 mmoles) in dry dimethylsulfoxide (DMSO) (7.5 mL) was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate (20 mL), washed with water (5 mL), dried and evaporated to dryness. To a solution of the residue in CHCl3 (5 mL) was added ether (50 mL) to give the quaternized blocked cephalosporin [XIIIa] (1.7 g), which was collected by filtration and treated with 90% trifluoroacetic acid [TFA] (17 mL) at room temperature for 1 hour. After evaporation of the solvent, the residue was triturated with ether, filtered and dissolved in CH3OH (2 mL). The solution was treated with 1M sodium 2-ethylhexanoate [SEH] in ethyl acetate (3.2 mL) at room temperature for 30 minutes to afford 774 mg of the crude title compound (Ia), which was purified by HPLC (Column, Lichrosorb RP-18, 8×300 mm; eluted with 0.01M ammonium phosphate buffer, pH 7.2--15% CH3OH) and HP-20 column chromatography (3×30 cm, washed with 1 L of water and eluted with 700 mL of 30% CH3OH). The fractions containing the desired product were collected, concentrated and lyophilized to afford 180 mg (22%) of the title compound (Ia) as a colorless powder, mp 165° C. (dec.).

Workup

  1. washwashed with water (5 mL)
  2. customdried
  3. customevaporated to dryness
  4. additionTo a solution of the residue in CHCl3 (5 mL) was added ether (50 mL)
  5. customto give the
  6. filtrationwas collected by filtration
  7. additiontreated with 90% trifluoroacetic acid [TFA] (17 mL) at room temperature for 1 hour
  8. customAfter evaporation of the solvent
  9. customthe residue was triturated with ether
  10. filtrationfiltered
  11. dissolutiondissolved in CH3OH (2 mL)
  12. additionThe solution was treated with 1M sodium 2-ethylhexanoate [SEH] in ethyl acetate (3.2 mL) at room temperature for 30 minutes
  13. customto afford 774 mg of the crude title compound (Ia), which
  14. customwas purified by HPLC (Column, Lichrosorb RP-18, 8×300 mm; eluted with 0.01M ammonium phosphate buffer, pH 7.2--15% CH3OH) and HP-20 column chromatography (3×30 cm, washed with 1 L of water and eluted with 700 mL of 30% CH3OH)
  15. additionThe fractions containing the desired product
  16. customwere collected
  17. concentrationconcentrated

Sources & evidence

ORD record
ord-425710920ba84fcc8dd64a8211a0c8bd
Source dataset
uspto-grants-1985_02
Patent number
US04500526

Reaction notes

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