合成路线1

The condensation of 2-amino-7-hydroxy-1,8-naphthyridine (I) with 5,6-dihydro-1,7-dithiin-2,3-dicarboxylic acid anhydride (II) in biphenyl-diphenyl ether at 230 C gives 5,7-dioxo-8-(7-hydroxy-1,8-naphthyridin-2-yl)-2,3,6,7-tetrahydro-5H-1,4-dithiino[2,3-c]pyrrole (III), which by reaction with POCl3 at 100 C is converted to the corresponding 7-chloro derivative (IV). Partial reduction of (IV) with KBH4 in methanol yields 6-(7-chloro-1,8-naphthyridin 2-yl)-5-hydroxy-7-oxo-2,3,6,7-tetrahydro-5H-1,4-dithiino[2,3-c]pyrrole (V), which is condensed with 4-chlorocarbonyl-1-(tert-butoxycarbonyl)piperazin (VI) by means of NaH in DMF affording 5-[(4-tert-butoxycarbonylpiperazin-1-yl)carbonyloxy]-6-(7-chloro-1,8-naphthyndin-2-yl)-7-oxo-2,3,6,7-tetrahydro-5H-1,4-dithiino[2,3-c]pyrrole (VII) Deprotection of (VII) by means of trifluoroacetic acid gives 6-(7-chloro-1,8-naphthyridin-2-yl)-7-oxo-5-[(piperazin-1-yl)carbonyloxy]-2,3,6,7-tetrahydro-5H-1,4-dithino[2,3-c]pyrrole (VIII), which is finally acetylated with propionic acid (IX) by means of dicyclohexylcarbodiimide in methylene chloride. The piperazine derivative (VI) is prepared as follows: The condensation of piperazine (X) with tert-butyl azidoformate (XI) in aqueous HCl gives 1-(tert-butoxycarbonyl)piperazine (XII), which is then condensed with phosgene in anhydrous toluene.