Mercaptoproline derivative (I) was condensed with protected piperazine (II) via activation with carbonyl diimidazole to afford amide (III). The 4-methoxybenzyl group of (III) was then removed with trifluoromethanesulfonic acid in the presence of anisole and trifluoroacetic acid, and the resulting mercaptan (IV) was condensed with carbapenem phosphate (VI), (prepared from ketone (V) and diphenylphosphorochloridate), to afford thioether (VII). N-Methylation was carried out using methyl fluorosulfonate to yield quaternary ammonium salt (VIII). Finally, the 4-nitrobenzyl ester and carbamate groups of (VIII) were eliminated by hydrogenation in the presence of Pd/C, and the target product was isolated by ion-exchange chromatography.

Mercaptoproline derivative (I) was condensed with N-(carbamoylmethyl)homopiperazine (II) via activation with carbonyl diimidazole to afford amide (III). The 4-methoxybenzyl group of (III) was then removed with trifluoromethanesulfonic acid in the presence of anisole and trifluoroacetic acid, and the resulting mercaptan (IV) was condensed with carbapenem phosphate (VI), (prepared from ketone (V) and diphenylphosphorochloridate), to afford thioether (VII). N-Methylation of (VII) was carried out using methyl fluorosulfonate to yield quaternary ammonium salt (VIII). Finally, the 4-nitrobenzyl ester and carbamate groups of (VIII) were eliminated by hydrogenation in the presence of Pd/C, and the target product was isolated by ion-exchange chromatography.

Mercaptoproline derivative (I) was condensed with protected piperazine (II) via activation with carbonyl diimidazole to afford amide (III). The 4-methoxybenzyl group of (III) was then removed with trifluoromethanesulfonic acid in the presence of anisole and trifluoroacetic acid, and the resulting mercaptan (IV) was condensed with carbapenem phosphate (VI), (prepared from ketone (V) and diphenylphosphorochloridate), to afford thioether (VII). N-Methylation was carried out using methyl fluorosulfonate to yield quaternary ammonium salt (VIII). Finally, the 4-nitrobenzyl ester and carbamate groups of (VIII) were eliminated by hydrogenation in the presence of Pd/C, and the target product was isolated by ion-exchange chromatography.

Mercaptoproline derivative (I) was condensed with N-(carbamoylmethyl)homopiperazine (II) via activation with carbonyl diimidazole to afford amide (III). The 4-methoxybenzyl group of (III) was then removed with trifluoromethanesulfonic acid in the presence of anisole and trifluoroacetic acid, and the resulting mercaptan (IV) was condensed with carbapenem phosphate (VI), (prepared from ketone (V) and diphenylphosphorochloridate), to afford thioether (VII). N-Methylation of (VII) was carried out using methyl fluorosulfonate to yield quaternary ammonium salt (VIII). Finally, the 4-nitrobenzyl ester and carbamate groups of (VIII) were eliminated by hydrogenation in the presence of Pd/C, and the target product was isolated by ion-exchange chromatography.