BMY-43351
Chemical Name: 7-[4-[4-(Cyclohexylmethyl)piperazin-1-yl]-4-oxobutoxy]-2,3-dihydro-1H-imidazo[4,5-b]quinolin-2-one dihydrochloride; 1-(Cyclohexylmethyl)-4-[4-(2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolin-7-yloxy)-1-oxobutyl]piperazine dihydrochloride
CAS No. 134346-48-8 (free base)
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:Alkylation of 5-hydroxy-2-nitrobenzaldehyde (I) with ethyl 4-bromobutyrate (II) in the presence of potassium carbonate at 110 C in DMF provided the aldehyde (III).Coupling of (III) with the phosphonate (IV) using triethylamine as the base afforded the unsaturated hydantoin derivative (V) as a mixture of geometrical isomers.Exhaustive catalytic hydrogenation of (V) over palladium on charcoal in DMF furnished the saturated aniline (VI),which underwent acid-catalyzed cyclization-dehydration in methanol at reflux,followed by oxidation upon addition of a molar equivalent of iodine to give the imidazo[4,5-b]quinoline derivative (VII).Alkaline hydrolysis of (VII) provided acid (VIII),which was coupled with N-cyclohexylmethylpiperazine,using diphenylphosphoryl azide in DMF at room temperature,to furnish BMY 43351 (IX).The dihydrochloride salt of (IX) was prepared by dissolution of the free base in a solution of 10% hydrogen chloride in methanol and subsequent precipitation with diethyl ether.
📌 参考资料/链接：
参考文献标题:BMY 43351
文献作者:Russell,J.W.; Seiler,S.M.; Meanwell,N.A.; Fleming,J.S.
参考来源:Drugs Fut 1992,17(1),15
📄 详细内容
合成路线:Alkylation of 5-hydroxy-2-nitrobenzaldehyde (I) with ethyl 4-bromobutyrate (II) in the presence of potassium carbonate at 110 C in DMF provided the aldehyde (III).Coupling of (III) with the phosphonate (IV) using triethylamine as the base afforded the unsaturated hydantoin derivative (V) as a mixture of geometrical isomers.Exhaustive catalytic hydrogenation of (V) over palladium on charcoal in DMF furnished the saturated aniline (VI),which underwent acid-catalyzed cyclization-dehydration in methanol at reflux,followed by oxidation upon addition of a molar equivalent of iodine to give the imidazo[4,5-b]quinoline derivative (VII).Alkaline hydrolysis of (VII) provided acid (VIII),which was coupled with N-cyclohexylmethylpiperazine,using diphenylphosphoryl azide in DMF at room temperature,to furnish BMY 43351 (IX).The dihydrochloride salt of (IX) was prepared by dissolution of the free base in a solution of 10% hydrogen chloride in methanol and subsequent precipitation with diethyl ether.
参考文献标题:Diethyl 2,4-dioxoimidazolidine-5-phosphonates: Horner-Wadsworth-Emmons reagents for the mild and efficient preparations of C-5 unsaturated hydantoin derivatives
文献作者:Wedding,D.L.; Meanwell,N.A.; Roth,H.R.; Wright,J.J.K.; Smith,E.C.R.
参考来源:J Org Chem 1991,566897-904
产品链接: CAS No. 134346-48-8››