AMD-7049(free base), AMD-8664

Chemical Name: N-(2-Pyridinylmethyl)-N-[4-(1,4,7-triazacyclotetradecan-4-ylmethyl)benzyl]amine tetrahydrochloride
CAS No. 255383-00-7
项目整合开发状态: Preclinical
项目研究机构: AnorMED (Originator)
合成路线:The acylation of 1,7-heptanediamine (I) with 2-nitrobenzenesulfonyl chloride (II) by means of TEA in dichloromethane gives the bis sulfamide (III),which is submitted to macrocyclization with the dimesylate (IV) by means of Cs2CO3 in hot DMF,yielding the protected 1,4,7-triazacyclotetradecane (V).The cleavage of the phosphoryl group of (IV) with HBr in acetic acid affords the secondary amine (VI),which is alkylated with he benzyl chloride (VII) by means of K2CO3 in refluxing acetonitrile,providing the adduct (VIII).This compound is deprotected with K2CO3 in DMF and treated with HCl or HBr to furnish the corresponding target salts.

合成路线:The intermediate benzyl chloride (VII) is obtained as follows: The reduction of 4-(bromomethyl)benzoic acid methyl ester (IX) with DIBAL in dichloromethane gives 4-(bromomethyl)benzyl alcohol (X),which is condensed with sulfamide (XI) (obtained by sulfonation of 2-(aminomethyl)pyridine (XII) with sulfonyl chloride (II) and TEA),by means of K2CO3 in dichloromethane,yielding the disubstituted sulfamide (XIII).Finally,the hydroxymethyl group of (XIII) is treated with MsCl and TEA in refluxing dichloromethane to afford the target benzyl chloride (VII).