【结 构 式】 |
【药物名称】Clofurenadine hydrochloride, (?-BN-1267 【化学名称】(±)-3-(4-Chlorophenyl)-1,3-dihydro-3,6-dimethylfuro[3,4-c]pyridin-7-ol hydrochloride 【CA登记号】91868-84-7 (free base) 【 分 子 式 】C15H15Cl2NO2 【 分 子 量 】312.1983 |
【开发单位】Institut Henri Beaufour (Originator) 【药理作用】Histamine H1 Antagonists |
合成路线1
The synthesis of (rac)-BN-1267 is presented. The Grignard reaction of 2,2,8-trimethyl-5-formylpyrido[4,3-e]-1,3-dioxane (I) with 4-chloro phenyl magnesium bromide in refluxing ether gives 2,2,8-trimethyl-5-(4-chloro-alpha-hydroxybenzyl)pyrido[4,3-e]-1,3-dioxane (II), which by oxidation with MnO2 affords the corresponding ketone (III). The Grignard reaction of (III) with methyl maynesium iodide gives 2,2,8-trimethyl-5-(4-chloro-alpha-methyl-alpha-hydraxybenzyl)pyrido[4,3-e]-1,3-dioxane (IV), which is then hydrolyzed and cyclized by treatment with aqueous concentrated HCl.
【1】 De Salvia, R.; et al.; J Meet Franco-Ital Pharmacol Soc (June, Paris) 1984, 135, 1-2, 1. |
【2】 Esanu, A. (SCRAS (Societé de Conseils de Recherches et d'Applications Scientifiques)); Furo[3,4-c]pyridine derivatives and therapeutic compositions containing the same. BE 0899222; CH 660191; GB 2137618; JP 1984193888; US 4581363; US 4735950 . |
【3】 Esanu, A.; Etienne, A.; Laurent, J.-P.; Braquet, P.; Mencia Huerta, J.M. Clostre, F.; Touvay, C.; Clofurenadine hydrochloride. Drugs Fut 1987, 12, 7, 627. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(A) | 25127 | bromo(4-chlorophenyl)magnesium | 873-77-8 | C6H4BrClMg | 详情 | 详情 |
(I) | 28771 | 2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridine-5-carbaldehyde | C11H13NO3 | 详情 | 详情 | |
(II) | 28772 | (3-chlorophenyl)(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)methanol | C17H18ClNO3 | 详情 | 详情 | |
(III) | 28773 | (3-chlorophenyl)(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)methanone | C17H16ClNO3 | 详情 | 详情 | |
(IV) | 28774 | 1-(3-chlorophenyl)-1-(2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)-1-ethanol | C18H20ClNO3 | 详情 | 详情 |