ethyl 5-methoxy-1,2-dimethyl-4-nitro-1H-indole-3-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】26102

【品名】ethyl 5-methoxy-1,2-dimethyl-4-nitro-1H-indole-3-carboxylate

【CA登记号】

【分子式】C₁₄H₁₆N₂O₅

【分子量】292.29152

【元素组成】C 57.53% H 5.52% N 9.58% O 27.37%

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：(III)

Ethyl 5-hydroxy-2-methylindole (I) was dimethylated with iodomethane in the presence of KH to give (II). Nitration of (II) in AcOH afforded the 4-nitroindole (III) together with some 6-nitro isomer (IV), which were separated by column chromatography. Reduction of (III) with Sn and HCl yielded the 4-aminoindole (V). This was then oxidized with Fremy's salt to afford the corresponding indolequinone (VI) (1). Quinone (VI) was reduced to the hydroquinone (VII) with sodium dithionite, and this was further reduced with DIBAL-H to give, after oxidative work-up with FeCl3 to regenerate the quinone, the 3-(hydroxymethyl) indolequinone (VIII). Finally, substitution of the methoxy group of (VIII) with aziridine (IX) in DMF yielded the target compound (2).

参考文献中间体

合成目标

【1】 Beall, H.D.; Winski, S.; Swann, E.; Hudnott, A.R.; Cotterill, A.S.; O'Sullivan, N.; Green, S.J.; Bien, R.; Siegel, D.; Ross, D.; Moody, C.J.; Indolequinone antitumor agents: Correlation between quinone structure, rate of metabolism by recombinant human NAD(P)H:quinone oxidoreductase, and in vitro cytotoxicity. J Med Chem 1998, 41, 24, 4755.
【2】 Naylor, M.A.; et al.; Indolequinone antitumor agents: Reductive activation and elimination from (5-methoxy-1-methyl-4,7-dioxoindol-3-yl)methyl derivatives and hypoxia-selective cytotoxicity in vitro. J Med Chem 1998, 41, 15, 2720.

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)	26100	3-Carbethoxy-5-hydroxy-2-methylindole; 5-Hydroxy-2-methylindole-3-carboxylic acid ethyl ester; 5-Hydroxy-2-methyl-1H-indole-3-carboxylic acid ethyl ester	7598-91-6	C₁₂H₁₃NO₃	详情	详情
(II)	26101	ethyl 5-methoxy-1,2-dimethyl-1H-indole-3-carboxylate		C₁₄H₁₇NO₃	详情	详情
(III)	26102	ethyl 5-methoxy-1,2-dimethyl-4-nitro-1H-indole-3-carboxylate		C₁₄H₁₆N₂O₅	详情	详情
(IV)	26103	ethyl 5-methoxy-1,2-dimethyl-6-nitro-1H-indole-3-carboxylate		C₁₄H₁₆N₂O₅	详情	详情
(V)	26104	ethyl 4-amino-5-methoxy-1,2-dimethyl-1H-indole-3-carboxylate		C₁₄H₁₈N₂O₃	详情	详情
(VI)	26105	ethyl 5-methoxy-1,2-dimethyl-4,7-dioxo-4,7-dihydro-1H-indole-3-carboxylate		C₁₄H₁₅NO₅	详情	详情
(VII)	26106	ethyl 4,7-dihydroxy-5-methoxy-1,2-dimethyl-1H-indole-3-carboxylate		C₁₄H₁₇NO₅	详情	详情
(VIII)	26107	3-(hydroxymethyl)-5-methoxy-1,2-dimethyl-1H-indole-4,7-dione		C₁₂H₁₃NO₄	详情	详情
(IX)	10151	Ethyleneimine; Aziridine; Azirane	151-56-4	C₂H₅N	详情	详情

Extended Information