Potassium Iodide → (6R,7R)-3-[[5-amino-4-[[2-(2-aminoethylamino)-2-oxoacetyl]amino]-1-methylpyrazol-2-ium-2-yl]methyl]-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(2-carboxypropan-2-yloxyimino)acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Participants

Reaction Steps

To a solution of 4-methoxybenzyl 7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-tert-butoxycarbonyl-1-methylethoxyimino)acetamido]-3-chloromethyl-3-cephem-4-carboxylate (618 mg) in N,N-dimethylformamide (1.5 ml) was added N-(trimethylsilyl)acetamide (656 mg), and the mixture was stirred at room temperature for 40 minutes. To the solution was added potassium iodide (232 mg), and the mixture was stirred at room temperature for 35 minutes. To the reaction mixture was added a solution of tert-butyl {2-[(2-{[1-methyl-5-(tritylamino)-1H-pyrazol-4-yl]amino}-2-oxoacetyl)amino]ethyl}carbamate (626 mg) in N,N-dimethylformamide (3 ml), and the whole mixture was stirred at 35–40° C. for 24 hours. To the resulting reaction mixture was added ethyl acetate (50 ml), and the solution was washed successively with water (50 ml×2), 10% aqueous sodium trifluoroacetate solution (50 ml×2), and brine (50 ml), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated to about 10 ml in vacuo. The concentrate was poured into diisopropyl ether (60 ml), and the resulting precipitate was collected by filtration and dried in vacuo. To a solution of the solid in methylene chloride (2.9 ml) were added anisole (0.95 ml) and trifluoroacetic acid (2.9 ml). The resulting solution was stirred at room temperature for 4 hours and poured into diisopropyl ether (60 ml). The resulting precipitate was collected by filtration and dried in vacuo to give a crude product (770 mg), which was purified by preparative HPLC utilizing ODS column. The eluate containing a desired product was concentrated to about 30 ml in vacuo. The concentrate was adjusted to about pH 3 with concentrated hydrochloric acid and chromatographed on Diaion® HP-20 (Mitsubishi Chemical Corporation) eluting with 30% aqueous 2-propanol. The eluate was concentrated to about 10 ml in vacuo and lyophilized to give 3-{[3-amino-4-({2-[(2-aminoethyl)amino]-2-oxoacetyl}amino)-2-methyl-1-pyrazolio]methyl}-7β-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(1-carboxy-1-methylethoxyimino)acetamido]-3-cephem-4-carboxylate (31 mg) as an amorphous solid.

Provenance & Evidence