TC-2557(sesquifumarate), TC-2559
3-丁烯-1-胺,4-(5-乙氧基-3-吡啶基)-N-甲基-, (3E)- Chemical Name: 4-(5-Ethoxypyridin-3-yl)-N-methyl-3(E)-buten-1-amine D-galactarate (2:1)
CAS No. 326924-19-0, 189274-78-0 (free base), 212332-35-9 (sesquifumarate)
项目整合开发状态: Preclinical
项目研究机构: Targacept (Originator)
合成路线:Reaction of 3,5-dibromopyridine (I) with sodium ethoxide gave 3-bromo-5-ethoxypyridine (II).Palladium-catalyzed coupling of bromopyridine (II) with 3-buten-1-ol (III) yielded the pyridinylbutenol (IV),which was further converted to tosylate (V).Displacement of the tosylate group of (V) with methylamine then gave amine (VI).
📌 参考资料/链接：
参考文献标题:[3-(5-Ethoxypyridin)yl]-alkenyl 1 amine cpds.
文献作者:Caldwell,W.S.; Dull,G.M.; Miller,C.H.
参考来源:US 5616716
📄 详细内容
合成路线:Reaction of 3,5-dibromopyridine (I) with sodium ethoxide gave 3-bromo-5-ethoxypyridine (II).Palladium-catalyzed coupling of bromopyridine (II) with 3-buten-1-ol (III) yielded the pyridinylbutenol (IV),which was further converted to tosylate (V).Displacement of the tosylate group of (V) with methylamine then gave amine (VI).
参考文献标题:Pharmaceutical compsns.for prevention and treatment of central nervous system disorders
文献作者:Dull,G.M.; Dobson,G.P.; Caldwell,W.S.(R.J.Reynolds Tobacco Co.)
参考来源:WO 9740011
合成路线:In a related method,4-bromo-1-butene (VII) was reacted with methylamine to produce the secondary amine (VIII).After protection of (VIII) as the tert-butyl carbamate (IX),palladium-catalyzed coupling with 3-bromo-5-ethoxypyridine (II) furnished adduct (X).The N-Boc protecting group of (X) was then cleaved under acidic conditions to afford amine precursor (VI).The title hemigalactarate salt was finally prepared by treatment of amine (VI) with D-galactaric acid in aqueous ethanol.
参考文献标题:TC-2559: A novel orally active ligand selective at neuronal acetylcholine receptors
文献作者:Bencherif,M.; Bane,A.J.; Miller,C.H.; Dull,G.M.; Gatto,G.J.
参考来源:Eur J Pharmacol 2000,409(1),45