4-(2,3-dichlorophenyl)-5-(methoxycarbonyl)-2,6-dimethyl-1,4-dihydro-3-pyridinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】17945

【品名】4-(2,3-dichlorophenyl)-5-(methoxycarbonyl)-2,6-dimethyl-1,4-dihydro-3-pyridinecarboxylic acid

【CA登记号】105580-45-8

【分子式】C₁₆H₁₅Cl₂NO₄

【分子量】356.20484

【元素组成】C 53.95% H 4.24% Cl 19.91% N 3.93% O 17.97%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

Clevidipine is prepared by esterification of 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid monomethyl ester (I) with chloromethyl butyrate (II) by means of NaHCO3 in DMF at 80 oC (1) or refluxing acetonitrile (2).

参考文献中间体

合成目标

【1】 Andersson, K.H.; Nordlander, M.; Westerlund, R.C. (AstraZeneca plc); Short-acting dihydropyridines. EP 0726894; JP 1997504542; US 5856346; WO 9512578 .
【2】 Mattson, A.; Svensson, C.; Thornblom, K.; Odman, C. (AstraZeneca AB); New manufacturing process. CA 2349195; EP 1133473; US 6350877; WO 0031035 .
【3】 Castañer, J., Sorbera, L.A.; Clevidipine. Drugs Fut 2004, 29 (2): 105

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)	17945	4-(2,3-dichlorophenyl)-5-(methoxycarbonyl)-2,6-dimethyl-1,4-dihydro-3-pyridinecarboxylic acid	105580-45-8	C₁₆H₁₅Cl₂NO₄	详情	详情
(II)	17946	chloromethyl butyrate	33657-49-7	C₅H₉ClO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

参考文献中间体

合成目标

【1】 Andersson KH, Nordlander M, Westerlund RC, (AstraZeneca plc). Short-acting dihydropyridines. EP 0726894; JP 1997504542; US 5856346; WO 9512578.
【2】 Kosugi Y, Hori M, Nagasaka T. 1994. Synthesis of optically pure 1,4-dihydropyridine derivatives by means od diastereoisomeric separation of the Hantzsch intermediates bearing (R) -1-phenylethylamino group. Heterocycles, 39(2) : 591～602.
【3】 Mattson A, Svensson C, Thonblom K, et al. (AstraZeneca AB). New manufacturing process. CA 2349195; EP 1133473; US 6350877; WO 0031035.

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)	67067	(Z)-allyl 3-((1-phenylethyl)amino)but-2-enoate		C₁₅H₁₉NO₂	详情	详情
(III)	67068	1-methyl 5-vinyl 2-acetyl-3-(2,3-dichlorophenyl)-4-(1-((1-phenylethyl)amino)ethylidene)pentanedioate		C₂₇H₂₉Cl₂NO₅	详情	详情
(IV)	67069	3-allyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate		C₁₉H₁₉Cl₂NO₄	详情	详情
(V)	17945	4-(2,3-dichlorophenyl)-5-(methoxycarbonyl)-2,6-dimethyl-1,4-dihydro-3-pyridinecarboxylic acid	105580-45-8	C₁₆H₁₅Cl₂NO₄	详情	详情
(VI)	17946	chloromethyl butyrate	33657-49-7	C₅H₉ClO₂	详情	详情

Extended Information