MF-10058
Chemical Name: 5-[2-[4-[4-(Diethylamino)butyl]piperidin-1-yl]acetyl]-5H-dibenzo[b,f]azepine
CAS No. 315719-45-0
项目整合开发状态: Preclinical
项目研究机构: Mediolanum (Originator)
合成路线:Horner-Emmons reaction of 1-benzyl-4-piperidone (I) with triethyl 4-phosphonocrotonate (II) afforded the (piperidinylidene)butenoate (III).Catalytic hydrogenation of the double bond of (III) with concomitant N-debenzylation yielded the piperidinylbutanoate (IV).After reprotection as the N-benzyl derivative (V),reduction of the ester function of (V) using LiAlH4 gave alcohol (VI),which was further converted to mesylate (VII).Displacement of the mesylate group of (VII) with diethylamine produced diamine (VIII).The N-benzyl group of (VIII) was then deprotected by transfer hydrogenation to furnish piperidine (IX).The chloroacetyl derivative (XI) was prepared by acylation of iminodibenzyl (X) with chloroacetyl chloride.Chloride (XI) was finally condensed with piperidine (IX) in the presence of Na2CO3 and NaI to afford the title compound.
📌 参考资料/链接：
参考文献标题:Selective M2 muscarinic receptor antagonists having 5H-dibenz[b,f]azepine structure
文献作者:Imbimbo,B.P.; Mandelli,G.R.; Terni,P.M.L.; Maiorana,S.(Mediolanum Farmaceutici)
参考来源:WO 0102386
📄 详细内容
合成路线:Horner-Emmons reaction of 1-benzyl-4-piperidone (I) with triethyl 4-phosphonocrotonate (II) afforded the (piperidinylidene)butenoate (III).Catalytic hydrogenation of the double bond of (III) with concomitant N-debenzylation yielded the piperidinylbutanoate (IV).After reprotection as the N-benzyl derivative (V),reduction of the ester function of (V) using LiAlH4 gave alcohol (VI),which was further converted to mesylate (VII).Displacement of the mesylate group of (VII) with diethylamine produced diamine (VIII).The N-benzyl group of (VIII) was then deprotected by transfer hydrogenation to furnish piperidine (IX).The chloroacetyl derivative (XI) was prepared by acylation of iminodibenzyl (X) with chloroacetyl chloride.Chloride (XI) was finally condensed with piperidine (IX) in the presence of Na2CO3 and NaI to afford the title compound.
参考文献标题:Synthesis of new cardioselective M2 muscarinic receptor antagonists
文献作者:Mandelli,G.R.; Maiorana,S.; Terni,P.; Lamperti,G.; Colibretti,M.L.; Imbimbo,B.P.
参考来源:Chem Pharm Bull 2000,48(11),1611