JTP-20993, -Drug Synthesis Database

【结构式】

【药物名称】JTP-20993

【化学名称】2-[4-[2-(5-Methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]- malonic acid dimethyl diester

【CA登记号】

【分子式】C₂₄H₂₅NO₆

【分子量】423.46995

【开发单位】Japan Tobacco

【药理作用】ENDOCRINE DRUGS，ANTIDIABETIC DRUGS

合成路线1

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.

参考文献中间体

【1】 Shinkai, H.; et al.; Isoxazolidine-3,5-dione and noncyclic 1,3-dicarbonyl compounds as hypoglycemic agents. J Med Chem 1998, 41, 11, 1927.
【2】 Shinkai, H.; The isoxazolidine-3,5-dione hypoglycemic agent JTT-501 and other nonthiazolidinedione insulin sensitizers. Drugs Fut 1999, 24, 8, 893.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	41311	2-(benzoylamino)-4-methoxy-4-oxobutyric acid		C₁₂H₁₃NO₅	详情	详情
(II)	41312	methyl 3-(benzoylamino)-4-oxopentanoate		C₁₃H₁₅NO₄	详情	详情
(III)	41313	methyl 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)acetate		C₁₃H₁₃NO₃	详情	详情
(IV)	19874	2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)-1-ethanol		C₁₂H₁₃NO₂	详情	详情
(V)	41315	2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethyl methanesulfonate		C₁₃H₁₅NO₄S	详情	详情
(VI)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(VII)	19372	4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde		C₁₉H₁₇NO₃	详情	详情
(VIII)	19374	dimethyl 2-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzylidene]malonate		C₂₄H₂₃NO₆	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(2)