Ozagrel sodium, Xanbon, Cataclot, -Drug Synthesis Database

【结构式】

【药物名称】Ozagrel sodium, Xanbon, Cataclot

【化学名称】(E)-p-(Imidazol-1-ylmethyl)cinnamic acid sodium salt
　　　　　　(E)-3-[4-(1H)-Imidazol-1-ylmethyl)phenyl]-2-propenoic acid sodium salt

【CA登记号】82571-53-7 (free acid)

【分子式】C₁₃H₁₁N₂NaO₂

【分子量】250.23462

【开发单位】Kissei (Originator), Ono (Originator)

【药理作用】Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Thromboxane Synthase Inhibitors

合成路线1 合成路线2

合成路线1

The condensation of ethyl 4-(bromomethyl)cinnamate (I) with imidazole (II) by means of NaH in DMF give ethyl 4-(1-imidazolylmethyl)cinnamate (III), wich is hydrolyzed with NaOH in methanol - water, and acidified with HCl.

参考文献中间体

【1】 Bergstrom, S.; Carlson, L.A.; Weeks, J.R.; The protaglandins: A family of biologically active lipids. J Med Chem 1981, 24, 10, 409-412.
【2】 Iizuka, K.; Akahane, K.; Kamijo, Y.; Momose, D.; Matsumoto, A.; Yukiyoshi, O. (Kissei Pharmaceutical Co., Ltd.; Ono Pharmaceutical Co., Ltd.); Imidazole derivative. DE 2923815; GB 2025946; US 4226878 .
【3】 Blancafort, P.; Serradell, M.N.; Pento, J.T.; Castaner, J.; OKY-046. Drugs Fut 1983, 8, 4, 328.

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)	30685	ethyl (E)-3-[4-(bromomethyl)phenyl]-2-propenoate; ethyl 4-(bromomethyl)cinnamate		C₁₂H₁₃BrO₂	详情	详情
(II)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情
(III)	30686	ethyl (E)-3-[4-(1H-imidazol-1-ylmethyl)phenyl]-2-propenoate; 4-(1-Imidazolylmethyl)cinnamate		C₁₅H₁₆N₂O₂	详情	详情

合成路线2

2-Methylimidazole (I) is converted into the bisulfate salt, and then nitrated by means of a sulfonitric mixture in Ac2O to produce 2-methyl-4-nitroimidazole (II) . In a variant of this procedure, 2-methylimidazole (I) is nitrated by using a ferric nitrate-tonsyl adduct in several solvents. Imidazole (II) is then regioselectively alkylated with boiling 2-chloroethanol to produce the title compound. Alternatively, the alkylation of (II) has been reported by treatment with ethylene oxide (III) under acidic conditions.

参考文献中间体

【1】 Frank, A.; Karn, H.; Spanig, H. (Abbott GmbH & Co. KG); Production of 1-hydroxyalkyl-5-nitroimidazoles. DE 2359625; FR 2253019; GB 1481349 .
【2】 Frank, A.; Dockner, T.; Karn, H. (Abbott GmbH & Co. KG); Process for the preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole of high purity. EP 0150407 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成

Extended Information