Temelastine, SK&F-93944

替美斯汀Chemical Name: 2-[4-(3-Bromo-5-methylpyridin-6-yl)butylamino]-5-(6-methylpyridin-3-ylmethyl)pyrimidin-4(1H)-one
CAS No. 86181-42-2
项目整合开发状态: Biological Testing
项目研究机构: GlaxoSmithKline (Originator)
合成路线:The condensation of diethyl 2-(2-cyanoethyl)malonate (I) with 2-chloro-3-methyl-5-nitropyridine (II) by means of NaH in refluxing THF gives 4-(3-methyl-5-nitropyrid-2-yl)-4,4-bis(ethoxycarbonyl)butyronitrile (III),which is decarboxylated with NaOH in ethanol water yielding 4-(3-methyl-5-nitropyrid-2-yl)butyronitrile (IV).The reduction of (IV) with H2 over Pd/C in ethanol affords 4-(5-amino-3-methylpyrid-2-yl)butyronitrile (V),which is reduced further with LiAlH4 in ether-THF giving 5-amino-2-(4-aminobutyl)-3-methylpyridine (VI).The Sandmeyer reaction of (VI) with NaNO2,HBr and Cu2Br2 yields 5-bromo-2-(4-aminobutyl)-3-methylpyridine (VII),which is finally condensed with 2-nitroamino-5-(6-methylpyrid-2-ylmethyl)-4-pyrimidone (VIII) in refluxing pyridine.