DHP-218

2,6-二甲基-4-(2-硝基苯基)-5-(2-氧代-1,3,2-二氧磷杂环己烷-2-基)-1,4-二氢吡啶-3-羧酸甲酯Chemical Name: Methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate
CAS No. 102097-78-9
项目整合开发状态: Phase III
项目研究机构: Nippon Shinyaku (Originator)
合成路线:The condensation of Cyclic acetonylphosphonate (II),obtained from bromoacetone and cyclic phosphite (I) by an Arbuzov reaction,with o-nitrobenzaldehyde in the presence of piperidine - AcOH salt in boiling benzene gives benzylidene phosphonale (III),which is cyclized with methyl 3-aminocrotonate (IV) in reflux in 2-propanol affording methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2 oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4 dihydro-pyridine-3 carboxylate.
📌 参考资料/链接:
参考文献标题:1,4-Dihydropyridine-3-carboxylate derivs.
文献作者:Kimura,K.; Morita,I.(Nippon Shinyaku Co.,Ltd.)
参考来源:AU 8541405; BE 0902210; EP 0159040; ES 8606276; FR 2563222; GB 2157695; JP 1985248693; US 5036059

📄 详细内容


合成路线:The condensation of Cyclic acetonylphosphonate (II),obtained from bromoacetone and cyclic phosphite (I) by an Arbuzov reaction,with o-nitrobenzaldehyde in the presence of piperidine - AcOH salt in boiling benzene gives benzylidene phosphonale (III),which is cyclized with methyl 3-aminocrotonate (IV) in reflux in 2-propanol affording methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2 oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4 dihydro-pyridine-3 carboxylate.

参考文献标题:DHP-218
文献作者:Kimura,K.
参考来源:Drugs Fut 1987,12(3),212


合成路线:The reaction of trimethylene glycol (I) with PCl3 gives 2-chloro-1,3,2-dioxaphosphorinane (II),which is condensed with propargyl alcohol (III) by means of triethylamine in acetonitrile to give a mixture of 2-allenyl- and 2-propargyl-2-oxo-1,3,2-dioxaphosphorinane (IV and V).The reaction of this mixture with isobutylamine in acetonitrile affords 2-(2-isobutylamino-1-propenyl)-2-oxo-1,3,2-dioxaphosphorinane (VI).The hydrolysis of the enamine (VI) with malonic acid gives 2-acetonyl-2-oxo-1,3,2-dioxaphosphorinane (VII),which is condensed with isobutyl-(2-nitrobenzylidene)amine (VIII) to yield 2-[1-(2-nitrobenzylidene)-2-oxopropyl]-2-oxo-1,3,2-dioxaphosphorinane (IX).Finally,this compound is cyclized with methyl 3-aminocrotonate (X) in refluxing acetonitrile.
参考文献标题:Improved synthesis of methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2-yl)-1,4-dihydropyridine-3-carboxylate (DHP-218)
文献作者:Morita,I.; Tsuda,M.; Kise,M.; Sugiyama,M.
参考来源:Chem Pharm Bull 1988,36(3),1139-42


产品链接: CAS No. 102097-78-9››