The intermediate 1-substituted imidazopyridine (III) was prepared by several procedures. Alkylation of imidazo[4,5-b]pyridine (I) with mesylate (II) in the presence of NaH provided a mixture of the desired compound (III) and its 3-substituted regioisomer (IV), which were separated by column chromatography.

In a different strategy, reductive alkylation of 2,3-diaminopyridine (V) with aldehyde (VI) using borane-pyridine complex yielded regioselectively the 3-alkylamino pyridine (VII). Subsequent cyclization of (VII) with triethyl orthoformate afforded the desired imidazopyridine (III). In an alternative, more direct procedure, the bicyclic compound (III) was obtained by reductive condensation of the 2-formamido derivative (VIII) with aldehyde (VI) in the presence of borane-pyridine complex.

Imidazopyridine (III) was alkylated either with the iodomethyl cephem derivative (IX) or with the chloromethyl analogue (X) in the presence of NaBr to obtain a mixture of the desired 4-alkylated imidazopyridinium salt (XI) and the 3-alkylated isomer (XII). After acidic cleavage of the N-Boc and PMB protecting groups of (XI) and (XII), the corresponding mixture of deprotected compounds was separated by column chromatography. The target 4-alkylated imidazopyridinium derivative was finally converted to the title sulfate salt.

The intermediate 1-substituted imidazopyridine (III) was prepared by several procedures. Alkylation of imidazo[4,5-b]pyridine (I) with mesylate (II) in the presence of NaH provided a mixture of the desired compound (III) and its 3-substituted regioisomer (IV), which were separated by column chromatography.

In a different strategy, reductive alkylation of 2,3-diaminopyridine (V) with aldehyde (VI) using borane-pyridine complex yielded regioselectively the 3-alkylamino pyridine (VII). Subsequent cyclization of (VII) with triethyl orthoformate afforded the desired imidazopyridine (III). In an alternative, more direct procedure, the bicyclic compound (III) was obtained by reductive condensation of the 2-formamido derivative (VIII) with aldehyde (VI) in the presence of borane-pyridine complex.

Imidazopyridine (III) was alkylated either with the iodomethyl cephem derivative (IX) or with the chloromethyl analogue (X) in the presence of NaBr to obtain a mixture of the desired 4-alkylated imidazopyridinium salt (XI) and the 3-alkylated isomer (XII). After acidic cleavage of the N-Boc and PMB protecting groups of (XI) and (XII), the corresponding mixture of deprotected compounds was separated by column chromatography. The target 4-alkylated imidazopyridinium derivative was finally converted to the title sulfate salt.

The intermediate 1-substituted imidazopyridine (III) was prepared by several procedures. Alkylation of imidazo[4,5-b]pyridine (I) with mesylate (II) in the presence of NaH provided a mixture of the desired compound (III) and its 3-substituted regioisomer (IV), which were separated by column chromatography.

In a different strategy, reductive alkylation of 2,3-diaminopyridine (V) with aldehyde (VI) using borane-pyridine complex yielded regioselectively the 3-alkylamino pyridine (VII). Subsequent cyclization of (VII) with triethyl orthoformate afforded the desired imidazopyridine (III). In an alternative, more direct procedure, the bicyclic compound (III) was obtained by reductive condensation of the 2-formamido derivative (VIII) with aldehyde (VI) in the presence of borane-pyridine complex.

Imidazopyridine (III) was alkylated either with the iodomethyl cephem derivative (IX) or with the chloromethyl analogue (X) in the presence of NaBr to obtain a mixture of the desired 4-alkylated imidazopyridinium salt (XI) and the 3-alkylated isomer (XII). After acidic cleavage of the N-Boc and PMB protecting groups of (XI) and (XII), the corresponding mixture of deprotected compounds was separated by column chromatography. The target 4-alkylated imidazopyridinium derivative was finally converted to the title sulfate salt.

The condensation of the aminocephem derivative (I) with the ethoxyiminoacetic acid (II) by means of POCl3 and NMM gives the corresponding amide (III), which is condensed with the imidazo pyridine (IV) by means of NaI or NaBr to yield the protected imidazopyridinium salt (V). Finally, this compound is deprotected by means of AlCl3 and anisole, TiCl4 and anisole or sulfuric and formic acids to afford the target cephem-carboxylate derivative.