5-methoxy-1H-indole-2-carboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】28885

【品名】5-methoxy-1H-indole-2-carboxylic acid

【CA登记号】4382-54-1

【分子式】C₁₀H₉NO₃

【分子量】191.1864

【元素组成】C 62.82% H 4.74% N 7.33% O 25.11%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The reaction of 5-methoxyindole-2-carboxylic acid (I) with thionyl chloride gives the acid chloride (II), which is condensed with dimethylamine to afford the amide (III). Reduction of (III) by LiAlH4 leads to the dimethylamino derivative (IV), which is quaternized by methyl iodide to give (V). The ammonium salt (V) is transformed into the corresponding phosphonium iodide (VI) by means of triphenyl phosphine. The successive steps from (I) to the phosphonium iodide (VI) give an overall yield of 50-60%. The condensation of (VI) with 4-formyl pyridine (VII) gives a mixture of 70% cis-(Z-VIII) and 30% trans-(E-VIII) isomers. The mixture of indolyl-pyridylethylenes (Z-VIII) and (E-VIII) is cyclized to 10-methoxy-7H-pyrido[4,3-c]carbazole (IX) by irradiation for 90 h in a Rayonet photoreactor at 350 nm in the presence of iodine (40% yield). Dimerization of (IX) is achieved by strirring in DMF two equivalents of (IX) with one equivalent of 1,1'-bis(2-chloroethyl)-4,4'-bipiperidine dihydrochloride (X) at 85 C for 18 h and recrystallization in EtOH/H20 (40/60).

参考文献中间体

合成目标

【1】 Bible, R.; Yuan, J.J.; Yang, D.-C.; Zhang, J.Y.; Findlay, J.W.; Karim, A.; Compt Rend Acad Sci 1976, 283, 9, 1109-1112.
【2】 Pelaprat. D.; et al.; DNA intercalating comnpounds as potential antitumor agents. 2. Preparation and properties of 7H-pyridocarbazole dimers. J Med Chem 1980, 23, 12, 1336-1343.
【3】 Pelaprat. D.; et al.; DNA intercalating comnpounds as potential antitumor agents. 1. Preparation and properties of 7H-pyridocarbazoles. J Med Chem 1980, 23, 12, 1330-1335.
【4】 Serradell, M.N.; Castaner, J.; Ditercalinium Chloride. Drugs Fut 1985, 10, 2, 116.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(Z-VIII)	28891	5-methoxy-2-[(Z)-2-(4-pyridinyl)ethenyl]-1H-indole		C₁₆H₁₄N₂O	详情	详情
(E-VIII)	28892	5-methoxy-2-[(E)-2-(4-pyridinyl)ethenyl]-1H-indole		C₁₆H₁₄N₂O	详情	详情
(I)	28885	5-methoxy-1H-indole-2-carboxylic acid	4382-54-1	C₁₀H₉NO₃	详情	详情
(II)	28885	5-methoxy-1H-indole-2-carboxylic acid	4382-54-1	C₁₀H₉NO₃	详情	详情
(III)	28887	5-methoxy-N,N-dimethyl-1H-indole-2-carboxamide		C₁₂H₁₄N₂O₂	详情	详情
(IV)	28888	(5-methoxy-1H-indol-2-yl)-N,N-dimethylmethanamine		C₁₂H₁₆N₂O	详情	详情
(V)	28889	(5-methoxy-1H-indol-2-yl)-N,N,N-trimethylmethanaminium iodide		C₁₃H₁₉IN₂O	详情	详情
(VI)	28890	[(5-methoxy-1H-indol-2-yl)methyl](triphenyl)phosphonium iodide		C₂₈H₂₅INOP	详情	详情
(VII)	17203	4-Pyridinecarboxaldehyde; isonicotinaldehyde	872-85-5	C₆H₅NO	详情	详情
(IX)	28893	10-methoxy-7H-pyrido[3,4-c]carbazole		C₁₆H₁₂N₂O	详情	详情
(X)	28894	1,1'-Bis-(2-chloro-ethyl)-[4,4']bipiperidinyl		C₁₄H₂₆Cl₂N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Bible, R.; Yuan, J.J.; Yang, D.-C.; Zhang, J.Y.; Findlay, J.W.; Karim, A.; Compt Rend Acad Sci 1976, 283, 9, 1109-1112.
【2】 Pelaprat. D.; et al.; DNA intercalating comnpounds as potential antitumor agents. 2. Preparation and properties of 7H-pyridocarbazole dimers. J Med Chem 1980, 23, 12, 1336-1343.
【3】 Pelaprat. D.; et al.; DNA intercalating comnpounds as potential antitumor agents. 1. Preparation and properties of 7H-pyridocarbazoles. J Med Chem 1980, 23, 12, 1330-1335.
【4】 Serradell, M.N.; Castaner, J.; Ditercalinium Chloride. Drugs Fut 1985, 10, 2, 116.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(Z-VIII)	28891	5-methoxy-2-[(Z)-2-(4-pyridinyl)ethenyl]-1H-indole		C₁₆H₁₄N₂O	详情	详情
(E-VIII)	28892	5-methoxy-2-[(E)-2-(4-pyridinyl)ethenyl]-1H-indole		C₁₆H₁₄N₂O	详情	详情
(I)	28885	5-methoxy-1H-indole-2-carboxylic acid	4382-54-1	C₁₀H₉NO₃	详情	详情
(II)	28885	5-methoxy-1H-indole-2-carboxylic acid	4382-54-1	C₁₀H₉NO₃	详情	详情
(III)	28887	5-methoxy-N,N-dimethyl-1H-indole-2-carboxamide		C₁₂H₁₄N₂O₂	详情	详情
(IV)	28888	(5-methoxy-1H-indol-2-yl)-N,N-dimethylmethanamine		C₁₂H₁₆N₂O	详情	详情
(V)	28889	(5-methoxy-1H-indol-2-yl)-N,N,N-trimethylmethanaminium iodide		C₁₃H₁₉IN₂O	详情	详情
(VI)	28890	[(5-methoxy-1H-indol-2-yl)methyl](triphenyl)phosphonium iodide		C₂₈H₂₅INOP	详情	详情
(VII)	17203	4-Pyridinecarboxaldehyde; isonicotinaldehyde	872-85-5	C₆H₅NO	详情	详情
(IX)	28893	10-methoxy-7H-pyrido[3,4-c]carbazole		C₁₆H₁₂N₂O	详情	详情
(X)	28894	1,1'-Bis-(2-chloro-ethyl)-[4,4']bipiperidinyl		C₁₄H₂₆Cl₂N₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VII)

The reaction of 3-amino-2-chloropyridine (I) with triethyl orthoacetate (II) catalyzed by TsOH gives the acetimidate (III), which is reduced to 3-(ethylamino)-2-chloropyridine (IV) by means of DIBAL in toluene. The reaction of (IV) with piperazine (V) by means of Na2CO3 by heating at 144 C affords 3-(ethylamino)-2-(1-piperazinyl)pyridine (VI), which is finally condensed with 5-methoxy-1H-indole-2-carboxylic acid (II) by means of CDI in dichloromethane and treated with CH3SO3H in methanol to provide the target mesylate.

参考文献中间体

合成目标

【1】 Perrault, W.R.; et al.; Production scale synthesis of the non-nucleoside recverse transcriptase inhibitor atervirdine mesylate (U-87,201E). Org Process Res Dev 1997, 1, 2, 106.

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)	11160	2-Chloro-3-pyridinamine; 2-Chloro-3-pyridinylamine; 3-Amino-2-chloropyridine; 2-Chloro-3-aminopyridine	6298-19-7	C₅H₅ClN₂	详情	详情
(II)	36531	1,1,1-trimethoxypropane; 1,1-dimethoxypropyl methyl ether		C₆H₁₄O₃	详情	详情
(III)	36532	methyl N-(2-chloro-3-pyridinyl)ethanimidoate		C₈H₉ClN₂O	详情	详情
(IV)	36533	N-(2-chloro-3-pyridinyl)-N-ethylamine; 2-chloro-N-ethyl-3-pyridinamine		C₇H₉ClN₂	详情	详情
(V)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(VI)	36534	N-ethyl-N-[2-(1-piperazinyl)-3-pyridinyl]amine; N-ethyl-2-(1-piperazinyl)-3-pyridinamine		C₁₁H₁₈N₄	详情	详情
(VII)	28885	5-methoxy-1H-indole-2-carboxylic acid	4382-54-1	C₁₀H₉NO₃	详情	详情

Extended Information