Aranidipine, MPC-1304, Bec, Sapresta
阿雷地平Chemical Name: (?-2,6-Dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid methyl 2-oxopropyl diester
CAS No. 86780-90-7
项目整合开发状态: Launched-1996
项目研究机构: Maruko (Originator), Bristol-Myers Squibb (Licensee), Taiho (Codevelopment)
合成路线:This compound can be prepared in two related ways:1) The condensation of diketene (I) with 2,2-(ethylenedioxy)propanol (II) by means of NaH in refluxing benzene gives 2,2-(ethylenedioxy)propyl acetylacetate (III),which is condensed with 2-nitrobenzaldehyde (IV) by means of piperidine and acetic acid in benzene,yielding 2,2-(ethylenedioxy)propyl 2-(2-nitrobenzylidene)acetoacetate (V).The cyclization of (V) with methyl 3-aminocrotonate (VI) in refluxing ethanol affords the protected dihydropyridine (VII),which is finally hydrolyzed with acetic acid in hot water.2) The reaction of the acetoacetate (III),obtained as before,with ammonia in methanol gives the 3-aminocrotonate (VIII),which is cyclized with methyl 2-(2-nitrobenzylidene)acetoacetate (IX) in refluxing ethanol to afford the dihydropyridine (VII),already obtained.
📌 参考资料/链接：
参考文献标题:Novel 1,4-dihydropyridines,especially useful as hypotensives
文献作者:Ohno,S.; Mizukoshi,K.; Komatsu,O.; Ichiara,K.; Morishima,T.(Maruko Seiyaku)
参考来源:FR 2514761
📄 详细内容
合成路线:This compound can be prepared in two related ways:1) The condensation of diketene (I) with 2,2-(ethylenedioxy)propanol (II) by means of NaH in refluxing benzene gives 2,2-(ethylenedioxy)propyl acetylacetate (III),which is condensed with 2-nitrobenzaldehyde (IV) by means of piperidine and acetic acid in benzene,yielding 2,2-(ethylenedioxy)propyl 2-(2-nitrobenzylidene)acetoacetate (V).The cyclization of (V) with methyl 3-aminocrotonate (VI) in refluxing ethanol affords the protected dihydropyridine (VII),which is finally hydrolyzed with acetic acid in hot water.2) The reaction of the acetoacetate (III),obtained as before,with ammonia in methanol gives the 3-aminocrotonate (VIII),which is cyclized with methyl 2-(2-nitrobenzylidene)acetoacetate (IX) in refluxing ethanol to afford the dihydropyridine (VII),already obtained.
参考文献标题:MPC-1304
文献作者:Castar,J.; Prous,J.
参考来源:Drugs Fut 1991,16(1),25
合成路线:This compound can be prepared in two related ways:1) The condensation of diketene (I) with 2,2-(ethylenedioxy)propanol (II) by means of NaH in refluxing benzene gives 2,2-(ethylenedioxy)propyl acetylacetate (III),which is condensed with 2-nitrobenzaldehyde (IV) by means of piperidine and acetic acid in benzene,yielding 2,2-(ethylenedioxy)propyl 2-(2-nitrobenzylidene)acetoacetate (V).The cyclization of (V) with methyl 3-aminocrotonate (VI) in refluxing ethanol affords the protected dihydropyridine (VII),which is finally hydrolyzed with acetic acid in hot water.2) The reaction of the acetoacetate (III),obtained as before,with ammonia in methanol gives the 3-aminocrotonate (VIII),which is cyclized with methyl 2-(2-nitrobenzylidene)acetoacetate (IX) in refluxing ethanol to afford the dihydropyridine (VII),already obtained.
参考文献标题:Synthesis of asymmetric 4-aryl-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylates with vasodilating and antihypertensive activities
文献作者:Sumita,T.; Nakamura,Y.; Ichihara,K.; Mizukoshi,K.; Komatsu,O.; Morishima,T.; Ohno,S.
参考来源:Chem Pharm Bull 1986,34(4),1589-606
产品链接: CAS No. 86780-90-7››