新产品编号:85937

Chemical Name: Glutaric acid 5,11-dimethyl-6H-pyrido[4,3-b]carbazol-9-yl monoester hydrochloride
CAS No. 160650-54-4, 160650-35-1 (monomethanesulfonate salt)
项目整合开发状态: Preclinical
项目研究机构: Tanabe Seiyaku (Originator)
合成路线:Treatment of 6-methoxy-1,4-dimethylcarbazole (I) with pivaloyl chloride and NaI in refluxing acetonitrile cleaved the methyl ether and afforded pivalate (II).The condensation of this with the Vilsmeier reagent from N-methylformanilide and phosphoryl chloride gave the formyl compound (III).Condensation of (III) with aminoacetaldehyde diethyl acetal in the presence of a catalytic amount of p-toluenesulfonic acid in refluxing toluene with azeotropic distillation of water,followed by hydrogenation of the intermediate imine in the presence of PtO2,afforded the corresponding amine,which was subsequently converted to the N-tosyl derivative (IV) on treatment with tosyl chloride and triethylamine.Refluxing (IV) with hydrogen chloride in aqueous dioxane effected cyclization,with simultaneous elimination of the tosyl and pivaloyl groups yielding the 9-hydroxyellipticine (V) (1).Glutaric acid monobenzyl ester (VIa) was converted to the active ester (VII) on treatment with 1-hydroxybenzotriazole (VIb) and dicyclohexyl carbodiimide,and this was condensed with (V) to afford diester (VIII).Finally,the benzyl ester was deprotected by hydrogenolysis in the presence of palladium-carbon and hydrogen.