占诺美林 (2R,3R)-2,3-二羟基丁二酸:3-己氧基-4-(1-甲基-3,6-二氢-2H-吡啶-5-基)-1,2,5-噻二唑 诺美林草酸盐Chemical Name: 3-Hexyloxy-4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazole
CAS No. 131986-45-3, 152854-19-8 (monotartrate), 141064-23-5 (oxalate salt)
项目整合开发状态: Phase II
项目研究机构: Lilly (Originator), Novo Nordisk (Originator)
合成路线:The reaction of pyridine-3-carbaldehyde (I) with KCN in acetic acid,followed by a treatment with NH4Cl in aqueous NH4OH yields 2-amino-2-(3-pyridyl)acetonitrile (II),which is cyclized to 3-chloro-4-(3-pyridyl)-1,2,5-thiadiazole (III) by a treatment with S2Cl2 in DMF.The reaction of (III) with sodium hexyloxide in hexanol yields 3-(hexyloxy)-4-(3-pyridyl)-1,2,5-thiadiazole (IV),which is treated with methyl iodide in acetone to afford the corresponding N-methylpyridinium salt (V).Finally,this compound is hydrogenated with NaBH4 in ethanol and salified with oxalic or L-tartaric acid in acetone or isopropanol.
📄 详细内容
合成路线:The reaction of pyridine-3-carbaldehyde (I) with KCN in acetic acid,followed by a treatment with NH4Cl in aqueous NH4OH yields 2-amino-2-(3-pyridyl)acetonitrile (II),which is cyclized to 3-chloro-4-(3-pyridyl)-1,2,5-thiadiazole (III) by a treatment with S2Cl2 in DMF.The reaction of (III) with sodium hexyloxide in hexanol yields 3-(hexyloxy)-4-(3-pyridyl)-1,2,5-thiadiazole (IV),which is treated with methyl iodide in acetone to afford the corresponding N-methylpyridinium salt (V).Finally,this compound is hydrogenated with NaBH4 in ethanol and salified with oxalic or L-tartaric acid in acetone or isopropanol.
参考文献标题:Heterocyclic cpds.and their preparation and use
文献作者:Sauerberg,P.; Olesen,P.H.; Mitch,c.H.(Novo Nordisk A/S)
参考来源:EP 0687265; JP 1996507298; WO 9420495
合成路线:The reaction of pyridine-3-carbaldehyde (I) with KCN in acetic acid,followed by a treatment with NH4Cl in aqueous NH4OH yields 2-amino-2-(3-pyridyl)acetonitrile (II),which is cyclized to 3-chloro-4-(3-pyridyl)-1,2,5-thiadiazole (III) by a treatment with S2Cl2 in DMF.The reaction of (III) with sodium hexyloxide in hexanol yields 3-(hexyloxy)-4-(3-pyridyl)-1,2,5-thiadiazole (IV),which is treated with methyl iodide in acetone to afford the corresponding N-methylpyridinium salt (V).Finally,this compound is hydrogenated with NaBH4 in ethanol and salified with oxalic or L-tartaric acid in acetone or isopropanol.
参考文献标题:Heterocyclic chemistry
文献作者:Osborne,L.M.; Shipley,L.A.; Treppendahl,S.; Petersen,T.G.(Novo Nordisk A/S)
参考来源:US 5834495; WO 9429303
合成路线:The reaction of pyridine-3-carbaldehyde (I) with KCN in acetic acid,followed by a treatment with NH4Cl in aqueous NH4OH yields 2-amino-2-(3-pyridyl)acetonitrile (II),which is cyclized to 3-chloro-4-(3-pyridyl)-1,2,5-thiadiazole (III) by a treatment with S2Cl2 in DMF.The reaction of (III) with sodium hexyloxide in hexanol yields 3-(hexyloxy)-4-(3-pyridyl)-1,2,5-thiadiazole (IV),which is treated with methyl iodide in acetone to afford the corresponding N-methylpyridinium salt (V).Finally,this compound is hydrogenated with NaBH4 in ethanol and salified with oxalic or L-tartaric acid in acetone or isopropanol.
参考文献标题:Novel functional M1selective muscarinic agonists.Synthesis and structure-activity relationships of 3-(1,2,5-thiadiazolyl)-1,2,5,6-tetrahydro-1-methylpyridines
文献作者:Sauerberg,P.; Olesen,P.H.; Nielsen,S.; Treppendahl,S.P.; Sheardown,M.J.; Honore,T.; Mitch,C.H.; Ward,J.S.; Pike,A.J.; Bymaster,F.P.; et al.
参考来源:J Med Chem 1992,35(12),2274-83
合成路线:The reaction of pyridine-3-carbaldehyde (I) with KCN in acetic acid,followed by a treatment with NH4Cl in aqueous NH4OH yields 2-amino-2-(3-pyridyl)acetonitrile (II),which is cyclized to 3-chloro-4-(3-pyridyl)-1,2,5-thiadiazole (III) by a treatment with S2Cl2 in DMF.The reaction of (III) with sodium hexyloxide in hexanol yields 3-(hexyloxy)-4-(3-pyridyl)-1,2,5-thiadiazole (IV),which is treated with methyl iodide in acetone to afford the corresponding N-methylpyridinium salt (V).Finally,this compound is hydrogenated with NaBH4 in ethanol and salified with oxalic or L-tartaric acid in acetone or isopropanol.
参考文献标题:Xanomeline
文献作者:Graul,A.; Castar,J.
参考来源:Drugs Fut 1996,21(9),911