Felodipine, H-154/82, CGH-869, Prevex, Perfudal, Lexxel(Comb. with enalapril), Logimax, Splendil, Munobal, Modip, Flodil, Plendil, Hydac, -Drug Synthesis Database

【结构式】

【药物名称】Felodipine, H-154/82, CGH-869, Prevex, Perfudal, Lexxel(Comb. with enalapril), Logimax, Splendil, Munobal, Modip, Flodil, Plendil, Hydac

【化学名称】(±)-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

【CA登记号】86189-69-7, 72509-76-3 (undefined stereoch.)

【分子式】C₁₈H₁₉Cl₂NO₄

【分子量】384.26243

【开发单位】Asta Medica (Originator), AstraZeneca (Originator), Aventis Pharma (Originator), Kissei (Licensee), Merck & Co. (Licensee), Novartis (Licensee), Promed (Licensee)

【药理作用】Angina pectoris, Treatment of, CARDIOVASCULAR DRUGS, Hypertension, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Calcium Channel Blockers

合成路线1 合成路线2 合成路线3

合成路线1

By cyclization of methyl 2,3-dichlorobenzyldeneacetoacetate (I) with ethyl 3-aminocrotonate (II) in tert-butanol at room temperature.

参考文献中间体

【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.
【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 .
【3】 Blancafort, P.; Serradell, M.N.; Sneddon, J.M.; Castaner, J.; Felodipine. Drugs Fut 1982, 7, 3, 160.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	20790	Methyl (Z)-2,3-dichlorobenzyldeneacetoacetate; Methyl (Z)-2-acetyl-3-(2,3-dichlorophenyl)-2-propenoate	74073-22-6	C₁₂H₁₀Cl₂O₃	详情	详情
(II)	11975	Ethyl (E)-3-amino-2-butenoate	7318-00-5	C₆H₁₁NO₂	详情	详情

合成路线2

By cyclization of 2,3-dichlorobenzaldehyde (I) with 3-aminocrotonic acid ethyl ester (II) and acetylacetic acid methyl ester (III) in refluxing ethanol.

参考文献中间体

【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 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	14742	2,3-dichlorobenzaldehyde	6334-18-5	C₇H₄Cl₂O	详情	详情
(II)	11975	Ethyl (E)-3-amino-2-butenoate	7318-00-5	C₆H₁₁NO₂	详情	详情
(III)	11791	methyl 3-oxobutanoate; Methyl acetoacetate	105-45-3	C₅H₈O₃	详情	详情

合成路线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.

参考文献中间体

【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 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	20790	Methyl (Z)-2,3-dichlorobenzyldeneacetoacetate; Methyl (Z)-2-acetyl-3-(2,3-dichlorophenyl)-2-propenoate	74073-22-6	C₁₂H₁₀Cl₂O₃	详情	详情
(V)	11819	ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate	141-97-9	C₆H₁₀O₃	详情	详情

Extended Information