Cronidipine, LF-2.0254

氯硝地平Chemical Name: 2,6-Dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-[8-(4-chlorophenyl)-8-aza-1,4-dioxaspiro[4.5]deca-2-ylmethyl] 5-methyl diester
CAS No. 113759-50-5
项目整合开发状态: Discontinued
项目研究机构: Fournier (Originator), SORI (Originator)
合成路线:This compound can be obtained in two different ways:1) The reaction of 8-(4-chlorophenyl)-8-aza-1,4-dioxaspiro[4.5]decane-2-methanol (I) with 5-acetyl-2,2-dimethyl-1,3-dioxane-4,6-dione (acetylated Meldrum's acid,II) in refluxing toluene gives the corresponding acetylacetic ester (III),which by reaction with NH3 in dry dichloromethane is converted into the 3-aminocrotonic ester (IV).Finally,this compound is cyclized with methyl 2-(3-nitrobenzylidene)acetylacetate (V) in refluxing tert-butanol.2) The partial hydrolysis of 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-(2,2-dimethyl-1,3-dioxolan-4-ylmethyl) 5-methyl diester (VI) with HCl 1N in methanol gives the corresponding glycerol ester (VII),which is then spiranized with 1-(4-chlorophenyl)-4-piperidone (VIII) by means of p-toluenesulfonic acid in refluxing methanol.