Coluracetam, MKC-231
考拉西坦Chemical Name: 1-[N-(2,3-Dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl)carbamoylmethyl]pyrrolidin-2-one; N-(2,3-Dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-yl)-2-(2-oxopyrrolidin-1-yl)acetamide
CAS No. 135463-81-9
项目整合开发状态: Phase II
项目研究机构: Mitsubishi Chemical (Originator), Mitsubishi Pharma (Originator), Takeda (Codevelopment)
合成路线:The intermediate 2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-amine (IV) has been obtained by two different ways:The cyclization of the bicyclic isatin (I) with cyclohexanone,NH4OH and NH4OAc in methanol gives 2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-carboxamide (III),which is submitted to a Hofmann rearrangement by means of Br2 and NaOH in water to yield the intermediate amine (IV).The cyclization of 2-amino-4,5-dimethylfuran-3-carbonitrile (V) with cyclohexanone (II) by means of ZnCl2 in hot xylene or nitrobenzene gives directly the intermediate amine (IV).Finally,amine (IV) is condensed with 2-(2-oxopyrrolidin-1-yl)acetic acid methyl ester (VI) by means of NaH in NMP to provide the target amide.
📌 参考资料/链接：
参考文献标题:4-Acylaminopyridine derivs.
文献作者:Ninomiya,K.; Saito,K.; Sugano,M.; Tobe,A.; Morinaka,Y.; Bessho,T.; Harada,H.(Mitsubishi Chemical Corp.)
参考来源:EP 0427636; JP 1991151366; JP 1991218360; JP 1991218361; US 5397785; US 5536728; US 5861411
📄 详细内容
合成路线:The intermediate 2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-amine (IV) has been obtained by two different ways:The cyclization of the bicyclic isatin (I) with cyclohexanone,NH4OH and NH4OAc in methanol gives 2,3-dimethyl-5,6,7,8-tetrahydrofuro[2,3-b]quinolin-4-carboxamide (III),which is submitted to a Hofmann rearrangement by means of Br2 and NaOH in water to yield the intermediate amine (IV).The cyclization of 2-amino-4,5-dimethylfuran-3-carbonitrile (V) with cyclohexanone (II) by means of ZnCl2 in hot xylene or nitrobenzene gives directly the intermediate amine (IV).Finally,amine (IV) is condensed with 2-(2-oxopyrrolidin-1-yl)acetic acid methyl ester (VI) by means of NaH in NMP to provide the target amide.
参考文献标题:Design and syntheses of 4-acylaminopyridine derivatives: Novel high affinity choline uptake enhancers II
文献作者:Chaki,H.; et al.
参考来源:Bioorg Med Chem Lett 1995,5(14),1495
产品链接: CAS No. 135463-81-9››