2-Amino-3-(2-oxo-1,2-dihydro-4-quinolinyl)propionic acid -Drug Synthesis Database

【结构式】

【分子编号】10301

【品名】2-Amino-3-(2-oxo-1,2-dihydro-4-quinolinyl)propionic acid

【CA登记号】

【分子式】C₁₂H₁₂N₂O₃

【分子量】232.23896

【元素组成】C 62.06% H 5.21% N 12.06% O 20.67%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(IX)

3) The methylation of 3-(2-oxo-1,2-dihydroquinolin-4-yl)-(R,S)-alanine (IX) with SOCl2 and methanol yields the corresponding methyl ester (X), which is submitted to optical resolution with D-(-)-mandelic acid, affording adducts (XII) and (XIII). The hydrolytic treatment of (XII) and (XIII) with HCl and propylene oxide finally yields isomers (VIIr) and (VIIs), already obtained. Racemic OPC-12759 can also be resolved into its optical isomers by treatment with brucine and fractionated crystallization.

参考文献中间体

合成目标

【1】 Morita, S.; Yamasaki, K.; Shimizu, T.; Uchida, M.; Otsubo, K.; Kanbe, T.; Synthesis and antiulcer activity of optical isomers of 2-(4-chlorobenzoy lamino)-3-[2(1H)-quinolinon-4-yl]propionic acid (rebamipide). Chem Pharm Bull 1991, 39, 11, 2906.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII-S)	10299	(2S)-2-Amino-3-(2-oxo-1,2-dihydro-4-quinolinyl)propionic acid		C₁₂H₁₂N₂O₃	详情	详情
(VIIR)	10306	(2R)-2-Amino-3-(2-oxo-1,2-dihydro-4-quinolinyl)propionic acid		C₁₂H₁₂N₂O₃	详情	详情
(IX)	10301	2-Amino-3-(2-oxo-1,2-dihydro-4-quinolinyl)propionic acid		C₁₂H₁₂N₂O₃	详情	详情
(X)	10302	methyl 2-amino-3-(2-chloro-4-quinolinyl)propanoate		C₁₃H₁₃ClN₂O₂	详情	详情
(XI)	10303	(2R)-2-Hydroxy-2-phenylethanoic acid; R-(-)-Mandelic acid	611-71-2	C₈H₈O₃	详情	详情
(XII)	10304	compound with hydroxy-phenyl-acetic acid; 2-Amino-3-(2-oxo-1,2-dihydro-quinolin-4-yl)-propionic acid methyl ester		C₁₃H₁₄N₂O₃.C₈H₈O₃	详情	详情
(XIII)	10305	2-Amino-3-(2-oxo-1,2-dihydro-quinolin-4-yl)-propionic acid methyl ester; compound with hydroxy-phenyl-acetic acid		C₁₃H₁₄N₂O₃.C₈H₈O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The condensation of 4-(bromomethyl)quinolin-2(1H)-one (I) with diethyl acetamidomalonate (II) by means of sodium ethoxide in refluxing ethanol gives ethyl 2-acetamido-2-(ethoxycarbonyl)-3-(2-oxo-1,2-dihydroquinolin-4yl)propionate (III), which is submitted to a decarboxylative hydrolysis with refluxing 20% HCl yielding 3-(2-oxo-1,2-dihydroquinolin-4yl)alanine (IV). Finaily this compound is acylated with 4-chlorobenzoyl chloride by means of K2CO3 in acetone water.

参考文献中间体

合成目标

【1】 Kanbe, T.; Nakagawa, K.; Morita, S.; Uchida, M.; Komatsu, M.; Tabusa, F.; Studies on 2(1H)-quinolinone derivatives as gastri. Chem Pharm Bull 1985, 33, 9, 3775.
【2】 Uchida, M.; Komatsu, M.; Nakagawa, K. (Otsuka Pharmaceutical Co., Ltd.); Carbostyril derivs., process for their preparation. DE 3324034; US 4578381 .

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)	10288	4-(Bromomethyl)-2(1H)-quinolinone		C₁₀H₈BrNO	详情	详情
(II)	16710	Diethyl 2-(acetamido)malonate; Diethyl acetamidomalonate	1068-90-2	C₉H₁₅NO₅	详情	详情
(III)	23536	diethyl 2-(acetamido)-2-[(2-oxo-1,2-dihydro-4-quinolinyl)methyl]malonate		C₁₉H₂₂N₂O₆	详情	详情
(IV)	10301	2-Amino-3-(2-oxo-1,2-dihydro-4-quinolinyl)propionic acid		C₁₂H₁₂N₂O₃	详情	详情
(V)	10295	p-Chlorobenzoyl chloride; 4-Chlorobenzoyl chloride	122-01-0	C₇H₄Cl₂O	详情	详情

Extended Information