2-[2-(7-chloro[1,8]naphthyridin-2-yl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-6-methyl-3-oxoheptanoic acid -Drug Synthesis Database

【结构式】

【分子编号】47684

【品名】2-[2-(7-chloro[1,8]naphthyridin-2-yl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-6-methyl-3-oxoheptanoic acid

【CA登记号】

【分子式】C₂₄H₂₂ClN₃O₄

【分子量】451.9092

【元素组成】C 63.79% H 4.91% Cl 7.85% N 9.3% O 14.16%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(XIII)

The isoindolinone (VII) (racemic pagoclone) can also be obtained by reaction of isoindolinone (V) with SOCl2 in DMF to provide 3-chloro-2-(7-chloro-1,8-naphthyridin-2-yl)isoindolin-1-one (X), which is condensed with 3-oxo-6-methylheptanoic acid ethyl ester (XI) by means of NaH in DMF to yield 2-[2-(7-chloro-1,8-naphthyridin-2-yl)-3-oxoisoindolin-1-yl-6-methyl-3-oxoheptanoic acid ethyl ester (XII). Finally, this compound is decarboxylated to the indolinone (VII) by means of LiCl in refluxing DMSO/water. The racemic benzoic acid (VIII) can also be obtained by hydrolysis of the heptanoic ester (XII) with concentrated sulfuric acid to give the corresponding free acid (XIII), which is finally decarboxylated and hydrolyzed by means of NaOH in water.

参考文献中间体

合成目标

【1】 Silvestre, J.S.; Castaner, J.; Leeson, P.A.; Sorbera, L.A.; Pagoclone. Drugs Fut 2001, 26, 7, 651.
【2】 Bourzat, J.-D.; Cotrel, C.; Roussel, G.; Capet, M.; Labaudiniere, R.; Pitchen, P. (Aventis SA); Isoindolinone derivs.. AU 8781911; EP 0274930; FR 2607503; JP 1988154681; US 4960779 .
【3】 David-Comte, M.-T. (Aventis Pharma SA); Dextrorotatory isomer of a deriv. of 2-amino naphthyridine and its preparation. EP 0522971; FR 2678933 .
【4】 David-Comte, M.-T.; Roussel, G. (Aventis Pharma SA); Novel 2-aminonaphthyridine deriv., its preparation and its use. EP 0522969; FR 2678931 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(V)	11334	2-(7-Chloro[1,8]naphthyridin-2-yl)-3-hydroxy-1-isoindolinone	C₁₆H₁₀ClN₃O₂	详情	详情
(VII)	47678	2-(7-chloro[1,8]naphthyridin-2-yl)-3-(5-methyl-2-oxohexyl)-1-isoindolinone	C₂₃H₂₂ClN₃O₂	详情	详情
(VIII)	47679	(rac)-2-[1-[(7-chloro[1,8]naphthyridin-2-yl)amino]-6-methyl-3-oxoheptyl]benzoic acid	C₂₃H₂₄ClN₃O₃	详情	详情
(X)	47681	3-chloro-2-(7-chloro[1,8]naphthyridin-2-yl)-1-isoindolinone	C₁₆H₉Cl₂N₃O	详情	详情
(XI)	47682	Ethyl isoamylacetoacetate; ethyl 6-methyl-3-oxoheptanoate	C₁₀H₁₈O₃	详情	详情
(XII)	47683	ethyl 2-[2-(7-chloro[1,8]naphthyridin-2-yl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-6-methyl-3-oxoheptanoate	C₂₆H₂₆ClN₃O₄	详情	详情
(XIII)	47684	2-[2-(7-chloro[1,8]naphthyridin-2-yl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-6-methyl-3-oxoheptanoic acid	C₂₄H₂₂ClN₃O₄	详情	详情

Extended Information