Methanol → 7-[2-(5-Amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-[3-(4-carbamoylpyridinio)-1-propenyl]-3-cephem-4-carboxylate

Participants

Reaction Steps

A mixture of diphenylmethyl 7-[2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetamido]-3-(3-iodo-1-propen-1-yl)-3-cephem-4-carboxylate (IX-1) (E isomer, 4.1 g, 5.7 mmoles) and isonicotinamide (1.4 g, 11 mmoles) in dry DMSO (6 ml) was stirred for 2 hours at room temperature while monitoring by TLC (silica gel plate, CHCl3 :CH3OH=3:1). The reaction mixture was diluted with ethyl acetate (100 ml) to separate a yellow gum, which was treated with formic acid (40 ml) and sodium bisulfite (390 mg) at 45° C. for 30 minutes. The resulting solution was concentrated to dryness. The residue was dissolved in H2O (100 ml) and insolubles were removed by filtration. The combined filtrate and water wash was applied to the top of a column containing reverse phase packing (PrepPAK-500/C18, 120 ml). The column was eluted with H2O. The eluate was collected in 300 ml fractions and monitored by uv (254 nm) and HPLC (Lichrosorb RP-18, 4×300 mm, 0.01M ammonium phosphate buffer, pH 7.2 containing 20% CH3OH). Fraction Nos. 4 and 5 were combined and concentrated to a small volume. Lyophilization gave 250 mg (8.1%) of the title compound I-1H, melting at >180° C. (dec.).

Provenance & Evidence