药物详细合成路线
| Name | Felodipine;H-154/82;CGH-869;Prevex;Perfudal;Lexxel(Comb. with enalapril);Logimax;Splendil;Munobal;Modip;Flodil;Plendil;Hydac | | Chemical Name | (±)-4-(2,3-Dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid ethyl methyl diester;(±)-4-(2,3-Dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3-ethoxycarbonyl-5-methoxycarbonylpyridine | | CAS | 86189-69-7 | | Related CAS | 72509-76-3 (undefined stereoch.) | | Formula | C18H19Cl2NO4 | | Structure |  | | Formula Weight | 384.26243 | | Stage | 上市-1988 | | Company | Asta Medica (Originator), AstraZeneca (Originator), Aventis Pharma (Originator), Kissei (Licensee), Merck & Co. (Licensee), Novartis (Licensee), Promed (Licensee) | | Activity/Mechanism | Angina pectoris, Treatment of, CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Calcium Channel Blockers | | Syn. Route | 3 | | Route 1 | | by cyclization of methyl 2,3-dichlorobenzyldeneacetoacetate (i) with ethyl 3-aminocrotonate (ii) in tert-butanol at room temperature. | | |  | | List of intermediates | No. | | 1-([[1-(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-2-oxohydrazino]carbonyl]oxy)-2,5-pyrrolidinedione | (ii) | | (3s,3ar,4s,4as,8ar,9as)-3-methyl-4-[(e)-2-[(2r,6s)-6-methylpiperidinyl]ethenyl]decahydronaphtho[2,3-c]furan-1(3h)-one | (i) | | | Reference 1: carter, r.e.; berntsson, p.; determination of te conformation of felodipine by 1h nmr-spinlattice relaxation time measurements. acta pharm suec 1981, 18, 221-226. Reference 2: bernston, p.b.; carlsson, s.a.i.; gaarder, j.o.; ljung, b.r. (astrazeneca ab); 2,6-dimethyl-4-2,3-disubstituted phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid-3,5-asymmetric diesters having hypotensive properties, as well as method for treating hypertensive conditions and pharmaceutical preparations containing same. ca 1117530; ep 0007293; jp 55009083; us 4264611 . Reference 3: blancafort, p.; serradell, m.n.; sneddon, j.m.; castaner, j.; felodipine. drugs fut 1982, 7, 3, 160. |
Route 2 | | by cyclization of 2,3-dichlorobenzaldehyde (i) with 3-aminocrotonic acid ethyl ester (ii) and acetylacetic acid methyl ester (iii) in refluxing ethanol. | | |  | | List of intermediates | No. | | 7-ethynyl-4,4-dimethyl-3,4-dihydro-1(2h)-naphthalenone | (iii) | | 1-([[1-(1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-2-oxohydrazino]carbonyl]oxy)-2,5-pyrrolidinedione | (ii) | | tert-butyl (1s)-1-[[(2,5-dioxo-2,5-dihydro-1h-pyrrol-1-yl)oxy]carbonyl]-2-methylpropylcarbamate | (i) | | | Reference 1: bernston, p.b.; carlsson, s.a.i.; gaarder, j.o.; ljung, b.r. (astrazeneca ab); 2,6-dimethyl-4-2,3-disubstituted phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid-3,5-asymmetric diesters having hypotensive properties, as well as method for treating hypertensive conditions and pharmaceutical preparations containing same. ca 1117530; ep 0007293; jp 55009083; us 4264611. |
Route 3 | | by cyclization of 2-(2,3-dichlorobenzylidene)acetyl acetic acid methyl ester (iv) with acetylacetic acid ethyl ester (v) and ammonia (vi) in tert-butanol. | | |  | | List of intermediates | No. | | 5-[4-hydroxy-2-(3-hydroxypentyl)-3,5,6-trimethylphenoxy]-2,2-dimethylpentanoic acid | (v) | | (3s,3ar,4s,4as,8ar,9as)-3-methyl-4-[(e)-2-[(2r,6s)-6-methylpiperidinyl]ethenyl]decahydronaphtho[2,3-c]furan-1(3h)-one | (iv) | | | Reference 1: bernston, p.b.; carlsson, s.a.i.; gaarder, j.o.; ljung, b.r. (astrazeneca ab); 2,6-dimethyl-4-2,3-disubstituted phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid-3,5-asymmetric diesters having hypotensive properties, as well as method for treating hypertensive conditions and pharmaceutical preparations containing same. ca 1117530; ep 0007293; jp 55009083; us 4264611. |
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来源:药化网
作者:药化小编
摘要:本文合成路线介绍的是药物中文名非洛地平；英文名Felodipine;H-154/82;CGH-869;Prevex;Perfudal;Lexxel(Comb. with enalapril);Logimax;Splendil;Munobal;Modip;Flodil;Plendil;Hydac；CAS[86189-69-7]
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