Alvameline tartrate, LU-25-109(free base), LU-25-109T
2-乙基-5-(1-甲基-1,2,3,6-四氢吡啶-5-基)-2H-四唑L-(+)-酒石酸盐 2-乙基-5-(1-甲基-1,2,5,6-四氢-吡啶-3-基)-2H-四唑 Chemical Name: 2-Ethyl-5-(1-methyl-1,2,3,6-tetrahydropyridin-5-yl)-2H-tetrazole L-(+)-tartrate; 5-(2-Ethyltetrazol-5-yl)-1-methyl-1,2,3,6-tetrahydropyridine L-(+)-tartrate
CAS No. 159792-14-0, 120241-31-8 (free base), 120241-32-9 (oxalate (1:1))
项目整合开发状态: Phase II
项目研究机构: Lundbeck (Originator), Forest (Licensee)
合成路线:The methylation of 3-cyanopyridine (I) with methyl iodide in acetone gives 3-cyano-1-methylpyridinium iodide (II),which is reduced with NaBH4 in methanol/water yielding 1-methyl-1,2,5,6-tetrahydropyridine-3-carbonitrile (III).The reaction of (III) with ethyl chloroformate and K2CO3 in 1,1,1-trichloroethane affords 3-cyano-1,2,5,6-tetrahydropyridine-1-carboxylic acid ethyl ester (IV),which is cyclized with sodium azide by means of AlCl3 in refluxing THF giving tetrazole (V).Alkylation of (V) with ethyl iodide and NaOH in refluxing acetone,followed by column chromatography,yields 3-(2-ethyltetrazol-5-yl)-1,2,5,6-tetrahydropyridine-1-carboxylic acid ethyl ester (VI).The decarboxylation of (VI) with HBr in acetic acid affords 2-ethyl-5-(1,2,5,6-tetrahydropyridin-3-yl)tetrazole (VII),which is methylated with formaldehyde/formic acid or with methyl iodide to give 2-ethyl-5-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)tetrazole (VIII).Finally,this compound is treated with L-(+)-tartaric acid.
📌 参考资料/链接：
参考文献标题:Bioisosteres of arecoline: 1,2,3,6-Tetrahydro-5-pyridyl-substituted and 3-piperidyl-substituted derivatives of tetrazoles and 1,2,3-triazoles.Synthesis and muscarinic activity
文献作者:Moltzen,E.K.; Pedersen,H.; Bogeso,K.P.; Meier,E.; Frederiksen,K.S.; Sanchez,C.; Love Lembol,H.
参考来源:J Med Chem 1994,37(24),4085-99
📄 详细内容
合成路线:The methylation of 3-cyanopyridine (I) with methyl iodide in acetone gives 3-cyano-1-methylpyridinium iodide (II),which is reduced with NaBH4 in methanol/water yielding 1-methyl-1,2,5,6-tetrahydropyridine-3-carbonitrile (III).The reaction of (III) with ethyl chloroformate and K2CO3 in 1,1,1-trichloroethane affords 3-cyano-1,2,5,6-tetrahydropyridine-1-carboxylic acid ethyl ester (IV),which is cyclized with sodium azide by means of AlCl3 in refluxing THF giving tetrazole (V).Alkylation of (V) with ethyl iodide and NaOH in refluxing acetone,followed by column chromatography,yields 3-(2-ethyltetrazol-5-yl)-1,2,5,6-tetrahydropyridine-1-carboxylic acid ethyl ester (VI).The decarboxylation of (VI) with HBr in acetic acid affords 2-ethyl-5-(1,2,5,6-tetrahydropyridin-3-yl)tetrazole (VII),which is methylated with formaldehyde/formic acid or with methyl iodide to give 2-ethyl-5-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)tetrazole (VIII).Finally,this compound is treated with L-(+)-tartaric acid.
参考文献标题:LU-25-109T
文献作者:Castar,J.; Mucke,H.A.M.
参考来源:Drugs Fut 1998,23(8),843-846
产品链接: CAS No. 159792-14-0›› 产品链接: CAS No.120241-31-8››