| 摘要 |
A process for preparing S-(-)-amlodipine.HCl is provided to improve preparation yield and purity of symmetric isomers by reducing the reaction steps and inhibiting side reactions, and inhibit explosion possibility of intermediates by using safe intermediates. A process for preparing S-(-)-amlodipine.HCl comprises the steps of: dissolving 2-(1,3-dimethylhexahydro-2-oxo-1,3,5-triazin-5-yl)ethanol represented by the formula(1) in organic solvent and reacting with metal haloacetate in the presence of base to prepare 2-(1,3-dimethylhexahydro-2-oxo-1,3,5-triazin-5-yl) represented by the formula(2); dissolving Im2CO(CD1, carbonyldiimidazol) represented by the formula(2) and 2,2-dimethyl-1,3-dioxan-4,6-dione in organic solvent, and reacting with ethanol in the presence of organic base to prepare ethyl-4-[2-(1,3-dimethylhexahydro-2-oxo-1,3,5-triazin-5-yl)ethoxy]-methyl-3-oxo-acetate represented by the formula(3); dissolving the compounds represented by the formula(3) and 2-chloro benzaldehyde in organic solvent, and reacting with (S)-(+)-2-methoxy-2-phenylethyl-3-amino isocrotonate represented by the formula(4) to prepare 2-[2-(1,3-dimethylhexahydro-2-oxo-1,3,5-triazin-5-yl)ethoxy]-methyl-4-(2-chlorophenyl)-3-ethoxy carbonyl-5-[(S)-(+)-2-methoxy-2-phenylethoxy carbonyl-6-methyl]-1,4-dihydro pyridine represented by the formula(5); dissolving the compounds represented by the formula(5) in organic solvent and reacting with base to prepare 2-[2-(1,3-dimethylhexahydro-2-oxo-1,3,5-triazin-5-yl)ethoxy]-methyl-4-(2-chlorophenyl)-3-ethoxy carbonyl-6-methyl]-1,4-dihydro pyridine represented by the formula(6); and dissolving the compounds represented by the formula(6) in organic solvent and reacting with anhydrous acid to prepare 2-(2-amino ethoxymethyl)-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarbonic acid-3-ethylester-5-methylester hydrochloric acid represented by the formula(7). |
