The mono-silylation of 2-aminoresorcinol (I) by means of tert-butyldimethylsilyl chloride and triethylamine yields silyl ether (II). Condensation of rifamycin S (III) with aminophenol (II), followed by oxidative treatment with MnO2 produces the benzoxazinorifamycin derivative (IV). Addition of N-propyl piperazine (V) to (IV) in the presence of MnO2 leads to the target piperazinyl benzoxazinorifamycin.
The benzoxazinorifamycin (III) was obtained by oxidative condensation of rifamycin S (I) with 2-aminoresorcinol (II). 1-Isobutylpiperazine (V), prepared by alkylation of piperazine (IV) with isobutyl bromide, was then coupled to the benzoxazine ring of (III) in the presence of MnO2 as the oxidant to afford the target piperazinyl derivative. In an improved procedure, 2-aminoresorcinol (II) was protected as the mono-silyl ether (VI) and subsequently coupled to rifamycin S (I) in the presence of MnO2, yielding (VII). Oxidative coupling of the benzoxazino derivative (VII) with 1-isobutylpiperazine (V) proceeded with simultaneous desilylation to furnish the title compound.