合成路线:The condensation of isopropyl acetoacetate (I) with 3-nitrobenzaldehyde (II) gives isopropyl 2-(3-nitrobenzylidene)acetoacetate (III),which is cyclized with methyl 3-amino-4,4-dimethoxycrotonate (IV) at 100 C yielding 5-isopropyl-3-methyl-2-(dimethoxymethyl)-6-methyl-4-(3-nitropheny)-1,4-dihydropyridine-3,5-dicarboxylate (V).The hydrolysis of the acetal group of (V) with HCl in acetone affords the corresponding 2-formyl derivative (VI),which is finally treated with hydroxylamine and acetic anhydride in acetic acid at 100 C.
参考文献标题:FR-34,235
文献作者:Blancafort,P.; Castar,J.; Serradell,M.N.
参考来源:Drugs Fut 1983,8(9),776
合成路线:1) The synthesis of deuterated nilvadipine has been reported:The selective hydrolysis of nilvadipine (I) with lithium iodide and pyridine gives the monolithium salt (II),which is then treated with perdeuterated methanol and 2-bromo-1-methylpyridinium bromide and dimethylaniline in DMF.
合成路线:2) The optical isomers of nilvidapine have also been synthesized:The selective hydrolysis of nilvadipine (I) with formic acid gives the monocarboxylic acid (II),which is treated with (-)-cinconidine,yielding the corresponding salt (IV) as a diastereomeric mixture,which is separated by fractional crystallization to give,after hydrolysis with HCl,2-cyano-3-(methoxycarbonyl)-6-methyl-4(R)-(3-nitrophenyl)-1,4-dihydropy ridine-5-carboxylic acid (Va) and 2-cyano-3-(methoxycarbonyl)-6-methyl-4(S)-(3-nitrophenyl)-1,4-dihydropy ridine-5-carboxylic acid (Vb) as pure optical isomers.Both compounds are esterified by conversion to the corresponding acyl chlorides with PCl5 and esterification with isopropyl alcohol.
参考文献标题:Studies on nilvadipine.IV.Synthesis of deuterated and optically active isopropyl 2-cyano-3-methoxycarbonyl-4-(3-nitrophenyl)-6-methyl-1,4-dihydropyridine-5-carboxylate (nilvadipine)
文献作者:Satoh,Y.; Okumura,K.; Shiokawa,Y.
参考来源:Chem Pharm Bull 1994,42(4),950
产品链接: CAS No. 75530-68-6››