AMD-3329
7,7'-(1,4-苯)双(甲基)双[4,7,10,17-四氮双环[11.3.1]十七-1(17),13,15-三烯] 八氢broidee 四水合物 4,7,10,17-四氮双环[11.3.1]十七-1(17),13,15-三烯,7,7'-[1,4-苯乙烯(甲基)]双- Chemical Name: 7,7'-(1,4-Phenylene)bis(methylene)bis[4,7,10,17-tetraazabicyclo[11.3.1]heptadeca-1(17),13,15-triene] octahydrobromide tetrahydrate
CAS No. 170861-77-5, 170861-87-7 (free base)
项目整合开发状态: Biological Testing
项目研究机构: Johnson Matthey (Originator), AnorMED (Licensee)
合成路线:Protection of the amino group of diethanolamine (I) with diethyl chlorophosphate in the presence of triethylamine gave N-(diethoxyphosphoryl)ethanolamine (II).Further treatment of (II) with methanesulfonyl chloride yielded the corresponding bis(mesylate) (III).Reaction of 2,6-bis(bromomethyl) pyridine (IV) with NaCN in the presence of cetyl trimethylammonium bromide under phase-transfer conditions produced dinitrile (V),which was hydrogenated over Raney Nickel to afford diamine (VI).Subsequent condensation of (VI) with p-toluenesulfonyl chloride gave bis(sulfonamide) (VII).Cyclization of bis(mesylate) (III) with bis(sulfonamide) (VII) in the presence of Cs2CO3 gave rise to macrocycle (VIII).Selective deprotection of the diethoxyphosphoryl group by means of HBr in AcOH gave (IX).This was dimerized with alpha,alpha'-dibromo-p-xylene (X) in the presence of K2CO3 in refluxing acetonitrile to give the tosyl-protected dimer (XI).Deprotection of the tosyl groups of (XI) was achieved by reductive treatment with sodium amalgam.The title compound was then isolated after conversion to the octahydrobromide tetrahydrate salt.
📌 参考资料/链接：
参考文献标题:Cyclic polyamines
文献作者:Bridger,G.J.; Padmanabhan,S.; Skerlj,R.T.(Johnson Matthey plc)
参考来源:EP 0739345; JP 1997509407; US 5698546; WO 9518808
📄 详细内容
合成路线:Protection of the amino group of diethanolamine (I) with diethyl chlorophosphate in the presence of triethylamine gave N-(diethoxyphosphoryl)ethanolamine (II).Further treatment of (II) with methanesulfonyl chloride yielded the corresponding bis(mesylate) (III).Reaction of 2,6-bis(bromomethyl) pyridine (IV) with NaCN in the presence of cetyl trimethylammonium bromide under phase-transfer conditions produced dinitrile (V),which was hydrogenated over Raney Nickel to afford diamine (VI).Subsequent condensation of (VI) with p-toluenesulfonyl chloride gave bis(sulfonamide) (VII).Cyclization of bis(mesylate) (III) with bis(sulfonamide) (VII) in the presence of Cs2CO3 gave rise to macrocycle (VIII).Selective deprotection of the diethoxyphosphoryl group by means of HBr in AcOH gave (IX).This was dimerized with alpha,alpha'-dibromo-p-xylene (X) in the presence of K2CO3 in refluxing acetonitrile to give the tosyl-protected dimer (XI).Deprotection of the tosyl groups of (XI) was achieved by reductive treatment with sodium amalgam.The title compound was then isolated after conversion to the octahydrobromide tetrahydrate salt.
参考文献标题:Synthesis and structure-activity relationships of phenylenebis (methylene)-linked bis-azamacrocycles that inhibit HIV-1 and HIV-2 replication by antagonism of the chemokine receptor CXCR4
文献作者:Bridger,G.J.; Skerlj,R.T.; Padmanabhan,S.; Martellucci,S.A.; Henson,G.W.; Struyf,S.; Witvrouw,M.; Schols,D.; De Clercq,E.
参考来源:J Med Chem 1999,42(19),3971
产品链接: CAS No. 170861-77-5›› 产品链接: CAS No.170861-87-7››