藥物詳細合成路線

Name	Difloxacin hydrochloride;A-56619;ABBOTT-56619
Chemical Name	1-(4-Fluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-7-(4-methyl-1-piperazinyl)quinoline-3-carboxylic acid hydrochloride
CAS	91296-86-5
Related CAS	98106-17-3 (free base)
Formula	C21H20ClF2N3O3
Structure
Formula Weight	435.86165
Stage	II 期臨床
Company	Abbott (Originator), Solvay (Licensee)
Activity/Mechanism	Antibacterial Drugs, ANTIINFECTIVE THERAPY, Quinolones
Syn. Route	1

Route 1 condensation of 2,4-dichoro-5-fluoroacetophenone (i) with diethyicarbonate (ii) in the presence of sodium hydride gives ethyl 2,4-dichloro-5-fluorobenzoylacetate (iii). the condensation of (iii) with triethylorthoformate in reftuxing acetic anhydride yields ethyl 2-(2,4-dichloro-5-fluornbenzoyl)-3-ethoxyacrylate (iv), which is treated with p-fluoroaniline in methylene chloride to yield ethyl 2-(2,4-dichloro-5-fluorobenzoyl)-3-(p-fluoroanilino)acrylate (v). cyclization of (v) with sodium hydride in tetrahydrofuran followed by hydrolysis yields 7-chloro-1-(p-fluorophenyl)-8 fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (vi). condensation of (vi) with n-methylpiperazine in 1-methyl-2-pyrrolidinone followed by treatment with hydrochloric acid yields a-56619. List of intermediates No. 5-(hydroxymethyl)-2-nitrophenol tert-butyl (1r,2r,4s)-2-(6-methoxy-3-pyridinyl)-7-azabicyclo[2.2.1]heptane-7-carboxylate (ii) 3-methoxy-5,11-dihydro-10h-dibenzo[a,d]cyclohepten-10-one (iii) ethyl 2-(3-methoxy-10,11-dihydro-5h-dibenzo[a,d]cyclohepten-10-yl)acetate (iv) n-(4-bromophenyl)-n-(methylsulfonyl)methanesulfonamide (i) n,n-bis(2-chloroethyl)-n-phenylurea (v) 1-(2-chloroethyl)-3-phenyl-2-imidazolidinone (vi) 1-(2-nitrophenyl)hydrazine Reference 1:     clairbone, a.k.; pihuleac, e.; nordeen, c.; fernandes, p.b.; pernet, a.; chu, d.t.w.; odonell, t.j.; a-56619 and a-56620: synthesis and antibacterial activities of the novel aryl-fluoro-quinolones and their analogs. 24th intersci conf antimicrob agents chemother (oct 8-10, washington, d.c) 1984, abs 72. Reference 2:     granneman, g.r.; chu, d.t.w.; fernandes, p.b.; abbott-56619. drugs fut 1985, 10, 7, 543.

來源:藥化網

作者:藥化小編

摘要:本文合成路線介紹的是藥物中文名鹽酸二氟沙星；英文名Difloxacin hydrochloride;A-56619;ABBOTT-56619；CAS[91296-86-5]

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