新产品编号:494093
Chemical Name: 4-Amino-N-[1-[1-(4-aminobutyl)piperidin-4-ylmethyl]piperidin-4-yl]-5-chloro-2-methoxybenzamide
CAS No. 220027-02-1
项目整合开发状态: Preclinical
项目研究机构: Dainippon Pharmaceutical (Originator)
合成路线:Isonipecotic acid (I) was protected with benzyl chloroformate and the resultant 1-(benzyloxycarbonyl)piperidine-4-carboxylic acid (II) was subsequently converted to the corresponding acid chloride (III) by treatment with SOCl2.Coupling of acid chloride (III) with 4-(tert-butoxycarbonylamino)piperidine (IV) afforded the piperidinyl amide (V),which was further reduced with BH3 to the piperidinylmethyl piperidine (VI).Aminopiperidine (VII),obtained by acidic cleavage of the N-Boc group of (VI),was then coupled with 4-amino-5-chloro-2-methoxybenzoic acid (VIII) to provide amide (IX).Deprotection of the N-benzyloxycarbonyl group was carried out by means of methanesulfonic acid in the presence of anisole to give (X).Acylation of piperidine (X) with the protected aminoacid (XI) yielded amide (XII).Then,selective reduction of the aliphatic amide function,followed by deprotection of the amino group provided the title compound.
📌 参考资料/链接：
参考文献标题:Benzamido derivs.and medicinal compsns.containing the same
文献作者:Kato,S.; Yoshida,N.; Harada,H.; Toyotomi,Y.; Morikage,S.(Dainippon Pharmaceutical Co.,Ltd.)
参考来源:JP 1999001472
📄 详细内容
合成路线:Isonipecotic acid (I) was protected with benzyl chloroformate and the resultant 1-(benzyloxycarbonyl)piperidine-4-carboxylic acid (II) was subsequently converted to the corresponding acid chloride (III) by treatment with SOCl2.Coupling of acid chloride (III) with 4-(tert-butoxycarbonylamino)piperidine (IV) afforded the piperidinyl amide (V),which was further reduced with BH3 to the piperidinylmethyl piperidine (VI).Aminopiperidine (VII),obtained by acidic cleavage of the N-Boc group of (VI),was then coupled with 4-amino-5-chloro-2-methoxybenzoic acid (VIII) to provide amide (IX).Deprotection of the N-benzyloxycarbonyl group was carried out by means of methanesulfonic acid in the presence of anisole to give (X).Acylation of piperidine (X) with the protected aminoacid (XI) yielded amide (XII).Then,selective reduction of the aliphatic amide function,followed by deprotection of the amino group provided the title compound.
参考文献标题:Novel N-[1-(1-substituted 4-piperidinylmethyl)-4-piperidinyl]benzamides as potent colonic prokinetic agents
文献作者:Harada,H.; Yamazaki,H.; Toyotomi,Y.; Tateishi,H.; Mine,Y.; Yoshida,N.; Kato,S.
参考来源:Bioorg Med Chem Lett 2002,12(6),967