Zonampanel, YM-872, -Drug Synthesis Database

【结构式】

【药物名称】Zonampanel, YM-872

【化学名称】2-[7-(1-Imidazolyl)-6-nitro-2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-1-yl]acetic acid

【CA登记号】210245-80-0, 179010-47-0 (monoHCl)

【分子式】C₁₃H₉N₅O₆

【分子量】331.24658

【开发单位】Yamanouchi (Originator)

【药理作用】Cerebrovascular Diseases, Treatment of, Ischemic Stroke, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, AMPA Antagonists, Kainate Antagonists

合成路线1 合成路线2

合成路线1

The title compound has been obtained by two related ways: Condensation of glycine ethyl ester (II) with 2,4-difluoronirobenzene (I) provided the N-arylglycine (III), which was further reduced to the phenylenediamine derivative (IV) by catalytic hydrogenation. Acylation of diamine (IV) with ethyl chloroglyoxylate, followed by ring closure in refluxing ethanol, yielded the quinoxalinedione (V). Subsequent electrophyllic nitration of (V) furnished the 6-nitroquinoxaline (VI). The fluoride group of (III) was then displaced with imidazole (VII) in hot DMF yielding the imidazolyl quinoxaline (VIII). Finally, basic hydrolysis of the ethyl ester function of (VIII) gave the target carboxylic acid.

参考文献中间体

【1】 Shishikura, J.; Inami, H.; Sakamoto, S.; Tsukamoto, S.; Sasamata, M.; Okada, M.; Fujii, M. (Yamanouchi Pharmaceutical Co., Ltd.); 1,2,3,4-Tetrahydroquinoxalindione deriv.. EP 0784054; US 6096743; WO 9610023 .

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)	32036	2,4-difluoro-1-nitrobenzene	446-35-5	C₆H₃F₂NO₂	详情	详情
(II)	10309	ethyl 2-aminoacetate; Glycine ethyl ester	459-73-4	C₄H₉NO₂	详情	详情
(III)	58528	ethyl 2-(5-fluoro-2-nitroanilino)acetate		C₁₀H₁₁FN₂O₄	详情	详情
(IV)	58529	ethyl 2-(2-amino-5-fluoroanilino)acetate		C₁₀H₁₃FN₂O₂	详情	详情
(V)	58530	ethyl 2-[7-fluoro-2,3-dioxo-3,4-dihydro-1(2H)-quinoxalinyl]acetate		C₁₂H₁₁FN₂O₄	详情	详情
(VI)	58531	ethyl 2-[7-fluoro-6-nitro-2,3-dioxo-3,4-dihydro-1(2H)-quinoxalinyl]acetate		C₁₂H₁₀FN₃O₆	详情	详情
(VII)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情
(VIII)	58532	ethyl 2-[7-(1H-imidazol-1-yl)-6-nitro-2,3-dioxo-3,4-dihydro-1(2H)-quinoxalinyl]acetate		C₁₅H₁₃N₅O₆	详情	详情

合成路线2

In a related procedure, the nitrophenyl imidazole (IX) was reduced to diamine (X) by catalytic hydrogenation. Acylation of diamine (X) with ethyl chloroglyoxylate, followed by ring closure, gave rise to quinoxaline (XI), which was then nitrated to afford (VIII) with fuming nitric acid. Finally, basic hydrolysis of the ethyl ester group of (VIII) as above, yielded the corresponding acid.

参考文献中间体

【1】 Shishikura, J.; Inami, H.; Sakamoto, S.; Tsukamoto, S.; Sasamata, M.; Okada, M.; Fujii, M. (Yamanouchi Pharmaceutical Co., Ltd.); 1,2,3,4-Tetrahydroquinoxalindione deriv.. EP 0784054; US 6096743; WO 9610023 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IX)	58533	ethyl 2-[5-(1H-imidazol-1-yl)-2-nitroanilino]acetate	C₁₃H₁₄N₄O₄	详情	详情
(X)	58534	ethyl 2-[2-amino-5-(1H-imidazol-1-yl)anilino]acetate	C₁₃H₁₆N₄O₂	详情	详情
(XI)	58535	ethyl 2-[7-(1H-imidazol-1-yl)-2,3-dioxo-3,4-dihydro-1(2H)-quinoxalinyl]acetate	C₁₅H₁₄N₄O₄	详情	详情
(XII)	58532	ethyl 2-[7-(1H-imidazol-1-yl)-6-nitro-2,3-dioxo-3,4-dihydro-1(2H)-quinoxalinyl]acetate	C₁₅H₁₃N₅O₆	详情	详情

Extended Information