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Milameline hydrochloride, Miramelin, CI-979, RU-35926, PD-129409

N-甲氧基-1-(1-甲基-5,6-二氢-2H-吡啶-3-基)甲烷亚胺盐酸盐 米拉美林 Chemical Name: (E)-1-Methyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde O-methyloxime monohydrochloride
CAS No. 139886-04-7, 139886-32-1 (free base), 114485-39-1 (free base, undefined stereoch.), 114485-44-8 (undefined stereoch.)
项目整合开发状态: Phase III
项目研究机构: Aventis Pharma (Originator), Pfizer (Originator)
合成路线:Milameline can be obtained by three related ways:1) By reaction of 1-methyl-1,2,3,6-tetrahydropyridine-3-carbaldehyde (I) with methoxyamine by means of triethylamine in DMF.2) The reaction of pyridine-3-carbaldehyde (II) with methoxyamine in refluxing methanol gives the corresponding oxime (III),which is alkylated with methyl iodide in refluxing ethyl acetate yielding 3-(methoxyiminomethyl)-1-methylpyridinium iodide (IV).Finally,this compound is hydrogenated with NaBH4 in methanol/water.3) The reaction of 1,2,3,6-tetrahydropyridine-3-carbaldehyde (V) with methoxyamine gives the corresponding oxime (VI),which is then alkylated with methyl iodide in DMF.
📌 参考资料/链接:
参考文献标题:1,2,5,6-Tetrahydropyridine-3-carboxaldehyde oxime derivs.,process for their preparation,their application as medicaments and compsns.containing them
文献作者:Galliani,G.; Barzaghi,F.; Butti,A.; Bonetti,C.; Toja,E.(Aventis Pharma SA)
参考来源:EP 0239445; JP 1987252767; US 5219872

📄 详细内容


合成路线:Milameline can be obtained by three related ways:1) By reaction of 1-methyl-1,2,3,6-tetrahydropyridine-3-carbaldehyde (I) with methoxyamine by means of triethylamine in DMF.2) The reaction of pyridine-3-carbaldehyde (II) with methoxyamine in refluxing methanol gives the corresponding oxime (III),which is alkylated with methyl iodide in refluxing ethyl acetate yielding 3-(methoxyiminomethyl)-1-methylpyridinium iodide (IV).Finally,this compound is hydrogenated with NaBH4 in methanol/water.3) The reaction of 1,2,3,6-tetrahydropyridine-3-carbaldehyde (V) with methoxyamine gives the corresponding oxime (VI),which is then alkylated with methyl iodide in DMF.

参考文献标题:O-Substd.tetrahydropyridine oxime cholinergic agents
文献作者:Bergmeier,S.C.; Downs,D.A.; Moos,W.H.; Moreland,D.W.; Tecle,H.(Pfizer Inc.)
参考来源:AU 8781102; EP 0271798; JP 1988215664; US 4710508


合成路线:Milameline can be obtained by three related ways:1) By reaction of 1-methyl-1,2,3,6-tetrahydropyridine-3-carbaldehyde (I) with methoxyamine by means of triethylamine in DMF.2) The reaction of pyridine-3-carbaldehyde (II) with methoxyamine in refluxing methanol gives the corresponding oxime (III),which is alkylated with methyl iodide in refluxing ethyl acetate yielding 3-(methoxyiminomethyl)-1-methylpyridinium iodide (IV).Finally,this compound is hydrogenated with NaBH4 in methanol/water.3) The reaction of 1,2,3,6-tetrahydropyridine-3-carbaldehyde (V) with methoxyamine gives the corresponding oxime (VI),which is then alkylated with methyl iodide in DMF.

参考文献标题:Milameline Hydrochloride
文献作者:Graul,A.; Castar,J.
参考来源:Drugs Fut 1996,21(11),1124


合成路线:Milameline can be obtained by three related ways:1) By reaction of 1-methyl-1,2,3,6-tetrahydropyridine-3-carbaldehyde (I) with methoxyamine by means of triethylamine in DMF.2) The reaction of pyridine-3-carbaldehyde (II) with methoxyamine in refluxing methanol gives the corresponding oxime (III),which is alkylated with methyl iodide in refluxing ethyl acetate yielding 3-(methoxyiminomethyl)-1-methylpyridinium iodide (IV).Finally,this compound is hydrogenated with NaBH4 in methanol/water.3) The reaction of 1,2,3,6-tetrahydropyridine-3-carbaldehyde (V) with methoxyamine gives the corresponding oxime (VI),which is then alkylated with methyl iodide in DMF.
参考文献标题:1-Alkyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-alkyl-oximes: A new class of potent orally active muscarinic agonists related to arecoline
文献作者:Toja,E.; Bonetti,C.; Butti,A.; Hunt,P.; Fortin,M.; Barzaghi,F.; Formento,M.L.; Maggioni,A.; Nencioni,A.; Galliani,G.
参考来源:Eur J Med Chem 1991,26(9),853-68


产品链接: CAS No. 139886-04-7››

产品链接: CAS No.139886-32-1››