DK-507K
Chemical Name: 7-[7(S)-Amino-5-azaspiro[2.4]hept-5-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride hydrate
CAS No. 364069-13-6, 364069-14-7 (free base), 364069-16-9 (hydrate), 364069-15-8 (hydrochloride), 364069-17-0 (methanesulfonate)
项目整合开发状态: Discontinued
项目研究机构: Daiichi Pharmaceutical (Originator), Pfizer (Licensee)
合成路线:The reaction of 2,4,5-trifluoro-3-methoxybenzoic acid (I) with SOCl2 in toluene gives the corresponding acyl chloride (II),which is condensed with 3-(dimethylamino)acrylic acid ethyl ester (III) by means of TEA to yield 3-(dimethylamino)-2-(2,4,5-trifluoro-3-methoxybenzoyl)acrylic acid ethyl ester (IV).The cyclization of (IV) with 2-fluorocyclopropylamine (V) by means of TEA and K2CO3 in DMF affords the quinolone-3-carboxylate (VI),which is hydrolyzed with HCl in HOAc to provide the carboxylic acid (VII).The reaction of (VII) with BF3/Et2O in diethyl ether gives the boronic ester (VIII),which is condensed with the spiropyrrolidine (IX) by means of TEA in ethanol.Finally,the boronic ester of (IX) is hydrolyzed with HCl to afford the target quinolone-3-carboxylic acid.
📌 参考资料/链接：
参考文献标题:Quinolonecarboxylic acid deriv.
文献作者:Suzuki,T.; Takahashi,H.; Hayakawa,I.; Takemura,M.; Ohtani,T.; Kawakami,K.; Itoh,M.; Miyauchi,R.; Sekiguchi,M.(Daiichi Pharmaceutical Co.,Ltd.)
参考来源:WO 0172738
📄 详细内容
合成路线:The reaction of 2,4,5-trifluoro-3-methoxybenzoic acid (I) with SOCl2 in toluene gives the corresponding acyl chloride (II),which is condensed with 3-(dimethylamino)acrylic acid ethyl ester (III) by means of TEA to yield 3-(dimethylamino)-2-(2,4,5-trifluoro-3-methoxybenzoyl)acrylic acid ethyl ester (IV).The cyclization of (IV) with 2-fluorocyclopropylamine (V) by means of TEA and K2CO3 in DMF affords the quinolone-3-carboxylate (VI),which is hydrolyzed with HCl in HOAc to provide the carboxylic acid (VII).The reaction of (VII) with BF3/Et2O in diethyl ether gives the boronic ester (VIII),which is condensed with the spiropyrrolidine (IX) by means of TEA in ethanol.Finally,the boronic ester of (IX) is hydrolyzed with HCl to afford the target quinolone-3-carboxylic acid.
参考文献标题:DK-570k,a new 8-methoxyquinolone: Synthesis and biological evaluation of 7-[(3-amino-4-substituted)pyrrolidin-1-yl] derivatives
文献作者:Kawakami,K.; et al.
参考来源:41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001,Chicago) 2001,Abst F-546
产品链接: CAS No. 364069-13-6›› 产品链接: CAS No.364069-14-7››