JTP-20993
Chemical Name: 2-[4-[2-(5-Methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]malonic acid dimethyl diester
CAS No. 170861-71-9
项目整合开发状态: Preclinical
项目研究机构: Japan Tobacco (Originator)
合成路线:Acetylation of N-benzoylaspartic acid beta-methyl ester (I) with acetic anhydride and subsequent decarboxylation gave the 3-benzoylamino-4-oxovalerate (II).The methyl oxazolylacetate (III) was prepared by cyclization of 4-oxovalerate (II) in the presence of Ac2O.Ester (III) was then reduced to alcohol (IV) with LiBH4 and further converted to mesylate (V) with methanesulfonyl chloride and Et3N.Coupling between mesylate (V) and 4-hydroxybenzaldehyde (VI) gave ether (VII).Knoevenagel condensation of (VII) with dimethyl malonate using piperidine acetate produced the benzylidene malonate (VIII).Finally,catalytic hydrogenation with Pd/C furnished the title compound.
📌 参考资料/链接：
参考文献标题:Isoxazolidine-3,5-dione and noncyclic 1,3-dicarbonyl compounds as hypoglycemic agents
文献作者:Shinkai,H.; Onogi,S.; Tanaka,M.; Shibata,T.; Iwao,M.; Wakitani,K.; Uchida,I.
参考来源:J Med Chem 1998,41(11),1927
📄 详细内容
合成路线:Acetylation of N-benzoylaspartic acid beta-methyl ester (I) with acetic anhydride and subsequent decarboxylation gave the 3-benzoylamino-4-oxovalerate (II).The methyl oxazolylacetate (III) was prepared by cyclization of 4-oxovalerate (II) in the presence of Ac2O.Ester (III) was then reduced to alcohol (IV) with LiBH4 and further converted to mesylate (V) with methanesulfonyl chloride and Et3N.Coupling between mesylate (V) and 4-hydroxybenzaldehyde (VI) gave ether (VII).Knoevenagel condensation of (VII) with dimethyl malonate using piperidine acetate produced the benzylidene malonate (VIII).Finally,catalytic hydrogenation with Pd/C furnished JTP-20993.The title compound (JTT-501) is obtained by reaction of JTP-20993 with NH2OH.
合成路线:Acetylation of N-benzoylaspartic acid beta-methyl ester (I) with acetic anhydride and subsequent decarboxylation gave the 3-benzoylamino-4-oxovalerate (II).The methyl oxazolylacetate (III) was prepared by cyclization of 4-oxovalerate (II) in the presence of Ac2O.Ester (III) was then reduced to alcohol (IV) with LiBH4 and further converted to mesylate (V) with methanesulfonyl chloride and Et3N.Coupling between mesylate (V) and 4-hydroxybenzaldehyde (VI) gave ether (VII).Knoevenagel condensation of (VII) with dimethyl malonate using piperidine acetate produced the benzylidene malonate (VIII).Finally,catalytic hydrogenation with Pd/C furnished the title compound.
参考文献标题:The isoxazolidine-3,5-dione hypoglycemic agent JTT-501 and other nonthiazolidinedione insulin sensitizers
文献作者:Shinkai,H.
参考来源:Drugs Fut 1999,24(8),893