CDD-0273, CDD-0273-A
Chemical Name: 3,3'-Oxybis(ethyleneoxy)bis(ethyleneoxy)bis[4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazole] dihydrochloride
CAS No. 331468-03-2, 331241-45-3 (free base)
项目整合开发状态: Biological Testing
项目研究机构: UCB Pharma (Originator), University of Toledo (Originator)
合成路线:The reaction of pyridine-3-carbaldehyde (I) with KCN in HOAc/water gives the cyanohydrine (II),which is treated with NH4Cl and NH3 in water to yield 2-amino-2-(3-pyridyl)acetonitrile (III).The cyclization of (III) with S2Cl2 in DMF affords 3-chloro-4-(3-pyridyl)-1,2,5-thiadiazole (IV),which is condensed with tetraethyleneglycol (V) by means of NaH in THF to provide the disubstituted tetraethyleneglycol (VI).The methylation of the pyridine rings of (VI) with methyl iodide in acetone gives the bis N-methylpyridinium derivative (VII),which is finally selectively reduced with NaBH4 in methanol and treated with HCl in the same solvent to furnish the target bis-tetrahydropyridine compound,isolated as the dihydrochloride salt.
📌 参考资料/链接：
参考文献标题:Muscarinic receptor agonists
文献作者:Cao,Y.; Rajeswaran,W.G.; Messer,W.S.(University of Toledo)
参考来源:US 6211204
📄 详细内容
合成路线:The reaction of pyridine-3-carbaldehyde (I) with KCN in HOAc/water gives the cyanohydrine (II),which is treated with NH4Cl and NH3 in water to yield 2-amino-2-(3-pyridyl)acetonitrile (III).The cyclization of (III) with S2Cl2 in DMF affords 3-chloro-4-(3-pyridyl)-1,2,5-thiadiazole (IV),which is condensed with tetraethyleneglycol (V) by means of NaH in THF to provide the disubstituted tetraethyleneglycol (VI).The methylation of the pyridine rings of (VI) with methyl iodide in acetone gives the bis N-methylpyridinium derivative (VII),which is finally selectively reduced with NaBH4 in methanol and treated with HCl in the same solvent to furnish the target bis-tetrahydropyridine compound,isolated as the dihydrochloride salt.
参考文献标题:Design,synthesis,and biological characterization of bivalent 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as selective muscarinic agonists
文献作者:Rajeswaran,W.G.; Cao,Y.; Huang,X.-P.; Wroblewski,M.E.; Colclough,T.; Lee,S.; Liu,F.; Nagy,P.I.; Ellis,J.D.; Levine,B.A.; Nocka,K.H.; Messer,W.S.Jr.
参考来源:J Med Chem 2001,44(26),4563