Indisetron hydrochloride, N-3389, Indisetron HCl Nisshin, Sinseron
1H-吆佐-3-羔酰胺,N-[(7-endo)-3,9-二甲基-3,9-二氮双环[3.3.1]非7-基]-,二盐酸盐(9CI)Chemical Name: N-(endo-3,9-Dimethyl-3,9-diazabicyclo[3.3.1]non-7-yl)-1H-indazole-3-carboxamide dihydrochloride
CAS No. 160472-97-9, 141549-75-9 (free base)
项目整合开发状态: Launched-2004
项目研究机构: Nisshin Pharma (Originator), Yakult Honsha (Marketer), Kyorin (Licensee)
合成路线:The condensation of bromoacetaldehyde dimethyl acetal (I) with methylamine (II) by means of KOH in refluxing ethylene glycol gives bis(2,2-dimethoxyethyl)methylamine (III),which is cyclized with acetonedicarboxylic acid (IV) and more methylamine (II),yielding 3,9-dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-one (V).The reaction of (V) with hydroxylamine affords the corresponding oxime (VI),which is reduced with H2 over RaNi in ethanol giving endo-3,9-dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-amine (VII).Finally,this compound is condensed with 1H-indazole-3-carbonyl chloride (VIII) by means of dimethylaminopyridine (DMAP) in pyridine.
📌 参考资料/链接：
参考文献标题:Azabicyclo derivs.and their use as antiemetics
文献作者:Kikuchi,H.; Satoh,H.; Yahata,N.; Hagihara,K.; Hayakawa,T.; Mino,S.; Yanai,M.(Nisshin Flour Milling Co.,Ltd.)
参考来源:EP 0469449; JP 1993310749; US 5187166
📄 详细内容
合成路线:The condensation of bromoacetaldehyde dimethyl acetal (I) with methylamine (II) by means of KOH in refluxing ethylene glycol gives bis(2,2-dimethoxyethyl)methylamine (III),which is cyclized with acetonedicarboxylic acid (IV) and more methylamine (II),yielding 3,9-dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-one (V).The reaction of (V) with hydroxylamine affords the corresponding oxime (VI),which is reduced with H2 over RaNi in ethanol giving endo-3,9-dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-amine (VII).Finally,this compound is condensed with 1H-indazole-3-carbonyl chloride (VIII) by means of dimethylaminopyridine (DMAP) in pyridine.
参考文献标题:N-3389
文献作者:Castar,J.; Rabasseda,X.; Mealy,N.
参考来源:Drugs Fut 1995,20(8),780
产品链接: CAS No. 160472-97-9›› 产品链接: CAS No.141549-75-9››