Gatifloxacin, BMS-206584, CG-5501, AM-1155, Zymar, Bonoq, Gatiflo, Tequin

盐酸加替沙星 加替沙星水合物 加替沙星Chemical Name: (?-1-Cyclopropyl-6-fluoro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
CAS No. 160738-57-8, 180200-66-2 (hydrate), 112811-59-3 (undefined isomer)
项目整合开发状态: Launched-1999
项目研究机构: Kyorin (Originator), Allergan (Licensee), Bristol-Myers Squibb (Licensee), Gr黱enthal (Licensee), Senju (Licensee), Dainippon Pharmaceutical (Comarketer), Lupin (Comarketer)
合成路线:The reaction of 1-bromo-2,4,5-trifluoro-3-methoxybenzene (I) with CuCN and N-methyl-2-pyrrolidone at 150 C gives 2,4,5-trifluoro-3-methoxybenzonitrile (II),which by treatment with concentrated H2SO4 yields the benzamide (III).The hydrolysis of (III) with H2SO4 - water at 110 C affords 2,4,5-trifluoro-2-methoxybenzoic acid (IV),which by reaction with SOCl2 is converted into the acyl chloride (V).The condensation of (V) with diethyl malonate by means of magnesium ethoxide in toluene affords diethyl 2-(2,4,5-trifluoro-3-methoxybenzoyl)malonate (VI),which by treatment with p-toluenesulfonic acid in refluxing water gives ethyl 2-(2,4,5-trifluoro-3-methoxybenzoyl)acetate (VII).The condensation of (VII) with triethyl orthoformate in refluxing acetic anhydride yields 3-ethoxy-2-(2,4,5-trifluoro-3-methoxybenzoyl)acrylic acid ethyl ester (VIII),which is treated with cyclopropylamine (IX) to afford the corresponding cyclopropylamino derivative (X).The cyclization of (X) by means of NaF in refluxing DMF gives 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (XI),which is hydrolyzed with H2SO4 in acetic acid to yield the corresponding free acid (XII).Finally,this compound is condensed with 2-methylpiperazine (XIII) in hot DMSO.