Pyrido benzothiazin-4-ones

Piperazine NH group of 9-fluoro-10-(l-piperazinyl)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-<7e]-l,4-benzothiazine-6-carboxylate was reacted with 4-nitrophenylsulfonyl chloride, 2,6-dichloropyrazine, 2,6-dichloropyridine in DMF in the presence of pyridine, and with 4-nitrophenyl isothiocyanate in aqueous acetone in the presence of KOH (01MIP13). A side chain amino group on a 2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazin-7-one skeleton was acylated (OOMIPIO). 

Reaction of 2-cyanomethyl-4H-l,3-benzothiazin-4-one with benzoylace-tonitrile at 160°C yielded 8-cyano-7-imino-9-phenyl-7//,ll//-pyrido[2,l-6][l,3]benzothiazin-l 1-one (85MI1 86MI2). Reaction of 2-ethoxy-2,3 dihydro-4//-l,3-benzothiazin-4-one with 1,2,3,4-tetramethylbutadiene and 2,4-dimethyl-l,3-pentadiene in the presence of boron trifluoride in diethyl ether gave rise to 6,7,8,9-tetramethyl- and 7,9)9-trimethyl-5a,6,9,ll-tetrahydropyrido[2,l-6][l,3]benzothiazin-ll-one, respectively (73JHC149). 

Optically active pipecolic acid and its derivatives can be prepared via 4-phenylpyrido[2,l-c][l,4]oxazin-l-one derivatives. Representatives of the third generation of quinoline-3-carboxylic acid antibacterial agents ofloxacin (19), its levorotatory enantiomer, levofloxacin (20), and rufloxacin (21) have gained wide acceptance for the treatment of bacterial infections of the respiratory and urinary tracts, skin, and soft tissues, as well as sexually transmitted diseases, and pazufloxacin (22) is under development. Other 10-aryl-9-fluoro-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-de]-l,4-benzox-azine-6-carboxylic acids and 7//-pyrido[l,2,3-de]-l,4-benzothiazine-6-carboxylic acids exhibit mammalian topoisomerase II inhibitory activity. 

Mixtures of l-(3-chloropropyl)-l,4-dihydro-2//-[3,l]benzothiazin-2-ones or their 3,3-dioxides and anhydrous AICI3 were stirred at ambient temperature for 30 min, and then at 170-180°C for 1 h, to give 1,5,6,7-tetrahydro-3i/-pyrido[3,2,l- ][3,l]benzothiazin-3-ones and their 2,2-dioxides [88JAP(K)88/170385]. 

Zinnes and co-workers prepared pyrido[l,2-b][l,2]benzothiazines (Scheme 8) 1,2-benzothiazine 182 with isopropyl iodide and potassium carbonate resulted in spontaneous aldol cyclization of the intermediate enol ether 183 to 7,8-dihydro-8-hydroxy-ll-isopropyloxy 8-substituted pyrido[l,2-b][l,2]benzothiazin-10(9//)-one 5,5 dioxide (184). In sulfuric acid, dehydration and ether cleavage of 184 gave the corresponding unsaturated )3-diketone 185. Hydrogenation gave the saturated analogs 186. An attempt to prepare 186 directly by base-catalyzed cyclization of 187 afforded a high yield of 2,3-dihydro-6/f-oxepino [3,2-c][l,2]benzothiazin-5(4H)-one 7,7-dioxide (188) (Eq. 39). 

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