Treatment of clarithromycin (I) with ethylene carbonate in refluxing triethylamine followed by dilute hydroalcoholic HCl removed the cladinose unit and dehydrated the C-11 hydroxyl to afford enone (II). Selective acetylation with acetic anhydride and triethylamine in dichloromethane gave the 2'-acetate (III), which was then mesylated at the 3-hydroxyl with methanesulfonic anhydride in pyridine to yield sulfonate (IV). Reaction of IV with carbonyldiimidazole (CDI) in DMF-THF, followed by NaH effected elimination of the methylsulfonyl group and gave the acylimidazole (V). Subsequent treatment of V with hydrazine in DMF, followed by methanolysis of the 2'-acetate gave a mixture of the epimeric carbazates (VI and VII) and the pyrazoline (VIII).

Chromatographic separation of the mixture afforded the desired 10(R)-carbazate (VII), which was reductively alkylated with 4-nitrocinnamaldehyde (IX) in the presence of sodium cyanoborohydride and acetic acid to yield the title compound.

Treatment of clarithromycin (I) with ethylene carbonate in refluxing triethylamine followed by dilute hydroalcoholic HCl removed the cladinose unit and dehydrated the C-11 hydroxyl to afford enone (II). Selective acetylation with acetic anhydride and triethylamine in dichloromethane gave the 2'-acetate (III), which was then mesylated at the 3-hydroxyl with methanesulfonic anhydride in pyridine to yield sulfonate (IV). Reaction of IV with carbonyldiimidazole (CDI) in DMF-THF, followed by NaH effected elimination of the methylsulfonyl group and gave the acylimidazole (V) (1). Subsequent treatment of V with hydrazine in DMF, followed by methanolysis of the 2'-acetate gave a mixture of the epimeric carbazates (VI and VII) and the pyrazoline (VIII).

Chromatographic separation of the mixture afforded the desired 10(R)-carbazate (VII), which was reductively alkylated with 4-nitrocinnamaldehyde (IX) in the presence of sodium cyanoborohydride and acetic acid to yield the 4-nitrocinnamyl compound (X). Finally, reduction with zinc dust in methanolic HCl gave the target aminocompound.

Treatment of clarithromycin (I) with ethylene carbonate in refluxing triethylamine followed by dilute hydroalcoholic HCl removed the cladinose unit and dehydrated the C-11 hydroxyl to afford enone (II). Selective acetylation with acetic anhydride and triethylamine in dichloromethane gave the 2'-acetate (III), which was then mesylated at the 3-hydroxyl with methanesulfonic anhydride in pyridine to yield sulfonate (IV). Reaction of IV with carbonyldiimidazole (CDI) in DMF-THF, followed by NaH effected elimination of the methylsulfonyl group and gave the acylimidazole (V). Subsequent treatment of V with hydrazine in DMF, followed by methanolysis of the 2'-acetate gave a mixture of the epimeric carbazates (VI and VII) and the pyrazoline (VIII).

Chromatographic separation of the mixture afforded the desired 10(R)-carbazate (VII), which was reductively alkylated with 4-nitrocinnamaldehyde (IX) in the presence of sodium cyanoborohydride and acetic acid to yield the title compound.

Treatment of clarithromycin (I) with ethylene carbonate in refluxing triethylamine followed by dilute hydroalcoholic HCl removed the cladinose unit and dehydrated the C-11 hydroxyl to afford enone (II). Selective acetylation with acetic anhydride and triethylamine in dichloromethane gave the 2'-acetate (III), which was then mesylated at the 3-hydroxyl with methanesulfonic anhydride in pyridine to yield sulfonate (IV). Reaction of IV with carbonyldiimidazole (CDI) in DMF-THF, followed by NaH effected elimination of the methylsulfonyl group and gave the acylimidazole (V) (1). Subsequent treatment of V with hydrazine in DMF, followed by methanolysis of the 2'-acetate gave a mixture of the epimeric carbazates (VI and VII) and the pyrazoline (VIII).

Chromatographic separation of the mixture afforded the desired 10(R)-carbazate (VII), which was reductively alkylated with 4-nitrocinnamaldehyde (IX) in the presence of sodium cyanoborohydride and acetic acid to yield the 4-nitrocinnamyl compound (X). Finally, reduction with zinc dust in methanolic HCl gave the target aminocompound.