Iganidipine hydrochloride, NKY-722
3,5-吡啶二羧酸,1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-,3-[2,2-二甲基-3-[4-(2-丙烯-1-基)-1-哌嗪酰]丙基] 5-甲基酯,盐酸盐(1:2) 伊加地平 Chemical Name: (?-2,6-Dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-[3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl] 5-methyl diester dihydrochloride
CAS No. 117241-46-0, 119687-33-1 (free base)
项目整合开发状态: Phase II
项目研究机构: Kyoto Pharmaceutical (Originator)
合成路线:Iganidipine can be obtained by two similar ways:1) The condensation of 1-(tert-butoxycarbonyl)piperazine (I) with isobutyraldehyde (II) and formaldehyde in acetic acid gives 3-[4-(tert-butoxycarbonyl)piperazin-1-yl]-2,2-dimethylpropionaldehyde (III),which is reduced with NaBH4 in isopropanol to the corresponding alcohol (IV).The condensation of (IV) with diketene (V) by mens of dimethylaminopyridine (DMAP) in dichloromethane affords the acetoacetic ester (VI),which is cyclized with 3-nitrobenzaldehyde (VII) and methyl 3-aminocrotonate (VIII) in refluxing isopropanol to give the protected dihydropyridine (IX).The elimination of the tert-butoxycarbonyl group of (IX) with HCl in ethanol yields dihydropyridine (X),which is finally alkylated with allyl chloride (XI) and triethylamine in hot THF.2) The condensation of 3-(4-allylpiperazin-1-yl)-2,2-dimethylpropanol (XII) with diketene (V) in dichloromethane gives the corresponding acetoacetic ester (XIII),which is treated with dry NH3 in methanol to yield the 3-aminocrotonic ester (XIV).Finally,this compound is cyclized with 2-(3-nitrobenzylidene)acetoacetic acid methyl ester (XV) in hot isopropanol.
📌 参考资料/链接：
参考文献标题:1,4-Dihydropyridine derivs.and pharmaceutical compsn.Thereof
文献作者:Matsui,H.; Fukata,F.M.; Mori,T.; Kakeya,N.; Kitao,K.(Kyoto Pharmaceutical Industries,Ltd.)
参考来源:AU 8812519; EP 0289746; JP 1988225355; US 4937242
📄 详细内容
合成路线:Iganidipine can be obtained by two similar ways:1) The condensation of 1-(tert-butoxycarbonyl)piperazine (I) with isobutyraldehyde (II) and formaldehyde in acetic acid gives 3-[4-(tert-butoxycarbonyl)piperazin-1-yl]-2,2-dimethylpropionaldehyde (III),which is reduced with NaBH4 in isopropanol to the corresponding alcohol (IV).The condensation of (IV) with diketene (V) by mens of dimethylaminopyridine (DMAP) in dichloromethane affords the acetoacetic ester (VI),which is cyclized with 3-nitrobenzaldehyde (VII) and methyl 3-aminocrotonate (VIII) in refluxing isopropanol to give the protected dihydropyridine (IX).The elimination of the tert-butoxycarbonyl group of (IX) with HCl in ethanol yields dihydropyridine (X),which is finally alkylated with allyl chloride (XI) and triethylamine in hot THF.2) The condensation of 3-(4-allylpiperazin-1-yl)-2,2-dimethylpropanol (XII) with diketene (V) in dichloromethane gives the corresponding acetoacetic ester (XIII),which is treated with dry NH3 in methanol to yield the 3-aminocrotonic ester (XIV).Finally,this compound is cyclized with 2-(3-nitrobenzylidene)acetoacetic acid methyl ester (XV) in hot isopropanol.
参考文献标题:3-Aminocrotonic acid ester
文献作者:Kakeya,N.; Fukada,F.; Nishizawa,S.(Kyoto Pharmaceutical Industries,Ltd.)
参考来源:JP 1991099064
合成路线:Iganidipine can be obtained by two similar ways:1) The condensation of 1-(tert-butoxycarbonyl)piperazine (I) with isobutyraldehyde (II) and formaldehyde in acetic acid gives 3-[4-(tert-butoxycarbonyl)piperazin-1-yl]-2,2-dimethylpropionaldehyde (III),which is reduced with NaBH4 in isopropanol to the corresponding alcohol (IV).The condensation of (IV) with diketene (V) by mens of dimethylaminopyridine (DMAP) in dichloromethane affords the acetoacetic ester (VI),which is cyclized with 3-nitrobenzaldehyde (VII) and methyl 3-aminocrotonate (VIII) in refluxing isopropanol to give the protected dihydropyridine (IX).The elimination of the tert-butoxycarbonyl group of (IX) with HCl in ethanol yields dihydropyridine (X),which is finally alkylated with allyl chloride (XI) and triethylamine in hot THF.2) The condensation of 3-(4-allylpiperazin-1-yl)-2,2-dimethylpropanol (XII) with diketene (V) in dichloromethane gives the corresponding acetoacetic ester (XIII),which is treated with dry NH3 in methanol to yield the 3-aminocrotonic ester (XIV).Finally,this compound is cyclized with 2-(3-nitrobenzylidene)acetoacetic acid methyl ester (XV) in hot isopropanol.
参考文献标题:Iganidipine Hydrochloride
文献作者:Robinson,C.P.; Robinson,K.A.; Castar,J.
参考来源:Drugs Fut 1997,22(1),23
产品链接: CAS No. 117241-46-0›› 产品链接: CAS No.119687-33-1››