Ofloxacin, Hoe-280, DL-8280, Exocin, Exocine, Ocuflox, Floxin, Tarivid

氧氟沙星Chemical Name: (?-9-Fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid
CAS No. 82419-36-1
项目整合开发状态: Launched-1985
项目研究机构: Daiichi Pharmaceutical (Originator), Allergan (Licensee), Aventis Pharma (Licensee), Ortho-McNeil (Licensee), Santen (Licensee)
合成路线:The partial hydrolysis ot 2,3,4-trifluoronitrobenzene (I) with KOH in DMSO gives 2,3-difluoro-6-nitrophenol (II),which by condensation with chloroacetone (III) by means of K2CO3 - KI in refluxing acetone yields 2-acetonyloxy-3,4-difluoronitrobenzene (IV).The reductive cyclization of (IV) with H2 over Raney-Ni in ethanol affords 7,8-difluoro-2,3-dihydro-3-methyl-4H-benzoxazine (V),which is condensed with diethyl ethoxymethylenemalonate (VI) by heating at 145 C giving the malonic derivative (VII).The cyclization of (VII) by heating at 145 C with ethyl polyphosphate (PPE) yields ethyl 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylate (VIII),which is hydrolyzed with HCl in refluxing acetic acid affording the corresponding free acid (IX).Finally,this compound is condensed with N-methylpiperazine (X) in DMSO at 110 C.