RP-60556A

合成路线:The condensation of 3,4-difluoroaniline (I) with 3-chloropropionyl chloride (II) and pyridine in hot acetone give the anilide (III),which is cyclized by means of AlCl3 at 110?C,yielding 6,7-difluoro-1,2,3,4-tetrahydroquinolin-2-one (IV).The reaction of (IV) with POCl3 and dimethylformamide affords the carbaldehyde (V),which is oxidized and aromatized by means of KMnO4 and KOH in water,providing 2-chloro-6,7-difluoroquinoline-3-carboxylic acid (VI).The reaction of (VI) with SOCl2 in chloroform gives the corresponding acyl chloride (VII),which is condensed with the magnesium salt of the malonic acid monoethyl ester (VIII) in THF to yield the 3-oxopropanoate (IX).The reaction of (IX) with dimethylformamide dimethylacetal (DMF) in hot ethyl acetate affords the 3-(dimethylamino)acrylate (X),which is cyclized by means of methylamine in ethanol to provide 7,8-difluoro-1-methyl-4-oxo-1,4-dihydrobenzo[g][1,8]naphthyridine-3-carboxylic acid ethyl ester (XI).The hydrolysis of (XI) with HCl in hot HOAc gives the corresponding carboxylic acid (XII) (1),which is condensed with 1-(4-fluorophenyl)piperazine (XIII) by heating at 90?C to yield the adduct (XIV).Finally,this compound is treated with choline hydroxide (XV) in methanol to afford the target choline salt.

参考文献标题:Synthesis and biological evaluation of RP60556A,a new topical antibacterial agent
文献作者:Tabart,M.; et al.
参考来源:40th Intersci Conf Antimicrob Agents Chemother (Sept 17 2000,Toronto) 2000,Abst F-1512


合成路线:The condensation of 3,4-difluoroaniline (I) with 3-chloropropionyl chloride (II) and pyridine in hot acetone give the anilide (III),which is cyclized by means of AlCl3 at 110?C,yielding 6,7-difluoro-1,2,3,4-tetrahydroquinolin-2-one (IV).The reaction of (IV) with POCl3 and dimethylformamide affords the carbaldehyde (V),which is oxidized and aromatized by means of KMnO4 and KOH in water,providing 2-chloro-6,7-difluoroquinoline-3-carboxylic acid (VI).The reaction of (VI) with SOCl2 in chloroform gives the corresponding acyl chloride (VII),which is condensed with the magnesium salt of the malonic acid monoethyl ester (VIII) in THF to yield the 3-oxopropanoate (IX).The reaction of (IX) with dimethylformamide dimethylacetal (DMF) in hot ethyl acetate affords the 3-(dimethylamino)acrylate (X),which is cyclized by means of methylamine in ethanol to provide 7,8-difluoro-1-methyl-4-oxo-1,4-dihydrobenzo[g][1,8]naphthyridine-3-carboxylic acid ethyl ester (XI).The hydrolysis of (XI) with HCl in hot HOAc gives the corresponding carboxylic acid (XII) (1),which is condensed with 1-(4-fluorophenyl)piperazine (XIII) by heating at 90?C to yield the adduct (XIV).Finally,this compound is treated with choline hydroxide (XV) in methanol to afford the target choline salt.
参考文献标题:Synthesis and biological evaluation of benzo[b]naphthyridones,a series of new topical antibacterial agents
文献作者:Tabart,M.; Picaut,G.; Desconclois,J.F.; Dutka-Malen,S.; Huet,Y.; Berthaud,N.
参考来源:Bioorg Med Chem Lett 2001,11(7),919