新产品编号:103339
Chemical Name: 2-(5-Methyl-2-phenyloxazol-4-ylmethoxy)-5-[3-(1H-tetrazol-5-yl)propyl]pyridine
CAS No. 166254-17-7
项目整合开发状态: Preclinical
项目研究机构: Takeda (Originator)
合成路线:Coupling of 2-chloro-5-nitropyridine (II) with the sodium alkoxide of 5-methyl-2-phenylisoxazol-4-ylmethanol (I) gave the 2-alkoxy-5-nitropyridine (III),which was reduced to the aminopyridine (IV) by catalytic hydrogenation over Pd/C.Meerwein arylation of methyl acrylate with the diazonium salt generated from amine (IV) furnished the bromopropionate (V),which was further dehydrohalogenated in the presence of DBU to the pyridyl acrylate (VI).Ester reduction in (VI) employing DIBAL yielded the allylic alcohol (VII).This was hydrogenated to the saturated alcohol (VIII) in the presence of Pd/C.After activation of alcohol (VIII) as the corresponding mesylate (IX),displacement by KCN in hot DMF yielded nitrile (X).This was finally converted to the desired tetrazole by treatment with sodium azide and ammonium chloride.
📌 参考资料/链接：
参考文献标题:Tetrazole derivs.,their production and use
文献作者:Sohda,T.; Ikeda,H.; Momose,Y.(Takeda Chemical Industries,Ltd.)
参考来源:CA 2125549; EP 0629624; JP 1995053555; US 5591862
📄 详细内容
合成路线:Coupling of 2-chloro-5-nitropyridine (II) with the sodium alkoxide of 5-methyl-2-phenylisoxazol-4-ylmethanol (I) gave the 2-alkoxy-5-nitropyridine (III),which was reduced to the aminopyridine (IV) by catalytic hydrogenation over Pd/C.Meerwein arylation of methyl acrylate with the diazonium salt generated from amine (IV) furnished the bromopropionate (V),which was further dehydrohalogenated in the presence of DBU to the pyridyl acrylate (VI).Ester reduction in (VI) employing DIBAL yielded the allylic alcohol (VII).This was hydrogenated to the saturated alcohol (VIII) in the presence of Pd/C.After activation of alcohol (VIII) as the corresponding mesylate (IX),displacement by KCN in hot DMF yielded nitrile (X).This was finally converted to the desired tetrazole by treatment with sodium azide and ammonium chloride.
参考文献标题:Novel 5-substituted-1H-tetrazole derivatives as potent glucose and lipid lowering agents
文献作者:Momose,Y.; Maekawa,T.; Odaka,H.; Ikeda,H.; Sohda,T.
参考来源:Chem Pharm Bull 2002,50(1),100