新产品编号:2072929
Chemical Name: N1-(Cyclohexylmethyl)-N4-[1-[2-(1-naphthyl)acetyl]piperidin-4-ylmethyl]butane-1,4-diamine hydrochloride
项目整合开发状态: Preclinical
项目研究机构: Daiichi Pharmaceutical (Originator)
合成路线:The primary amino group of 4-(aminomethyl)piperidine (I) was protected by conversion to the phthalimide (III) upon heating with phthalic anhydride (II).After coupling of piperidine (III) with 1-naphthylacetic acid (IV) to give amide (V),hydrazinolysis of the phthalimido group of (V) liberated the primary amine (VI).Alkylation of (VI) with N-(4-bromobutyl)phthalimide (VII) furnished the secondary amine (VIII),which was further protected with a tert-butoxycarbonyl group to provide (IX).The phthaloyl group of (IX) was then removed by hydrazinolysis,yielding amine (X).This was subjected to reductive alkylation with cyclohexanecarboxaldehyde (XI) in the presence of NaBH4 to afford the cyclohexylmethyl amine (XII).After purification as the di-Boc derivative,acid cleavage of the tert-butyl carbamate groups provided the title compound.
📌 参考资料/链接：
参考文献标题:Synthesis of diaminobutane derivatives as potent Ca2+-permeable AMPA receptor antagonists
文献作者:Yoneda,Y.; Kawajiri,S.; Sugimura,M.; Osanai,K.; Kito,F.; Ota,E.; Mimura,T.
参考来源:Bioorg Med Chem Lett 2001,11(19),2663
📄 详细内容
合成路线:The primary amino group of 4-(aminomethyl)piperidine (I) was protected by conversion to the phthalimide (III) upon heating with phthalic anhydride (II).After coupling of piperidine (III) with 1-naphthylacetic acid (IV) to give amide (V),hydrazinolysis of the phthalimido group of (V) liberated the primary amine (VI).Alkylation of (VI) with N-(4-bromobutyl)phthalimide (VII) furnished the secondary amine (VIII),which was further protected with a tert-butoxycarbonyl group to provide (IX).The phthaloyl group of (IX) was then removed by hydrazinolysis,yielding amine (X).This was subjected to reductive alkylation with cyclohexanecarboxaldehyde (XI) in the presence of NaBH4 to afford the cyclohexylmethyl amine (XII).After purification as the di-Boc derivative,acid cleavage of the tert-butyl carbamate groups provided the title compound.
参考文献标题:Discovery of diaminobutane derivatives as Ca2+ -permeable AMPA receptor antagonists
文献作者:Yoneda,Y.; Mimura,T.; Kawagoe,K.; Yasukouchi,T.; Tatematu,T.; Ito,M.; Saito,M.; Sugimura,M.; Kito,F.; Kawajiri,S.
参考来源:Bioorg Med Chem 2002,10(5),1347