5-Benzyloxyindole; benzyl 1H-indol-5-yl ether; 5-(benzyloxy)-1H-indole -Drug Synthesis Database

【结构式】

【分子编号】30840

【品名】5-Benzyloxyindole; benzyl 1H-indol-5-yl ether; 5-(benzyloxy)-1H-indole

【CA登记号】1215-59-4

【分子式】C₁₅H₁₃NO

【分子量】223.27436

【元素组成】C 80.69% H 5.87% N 6.27% O 7.17%

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：(I)

The N-benzyl indole derivative (III) was prepared by alkylation of 5-(benzyloxy)indole (I) with benzyl bromide (II) in the presence of KOH. The O-benzyl protecting group of (III) was subsequently removed by transfer hydrogenolysis with ammonium formate and Pd/C to afford the 5-hydroxyindole (IV), which was further condensed with 3-chloro-4-fluorobenzonitrile (V) to produce the diaryl ether (VI). Finally, basic hydrolysis of the cyano group of (VI) gave the corresponding benzoic acid.

参考文献中间体

合成目标

【1】 Mase, T.; Inami, H.; Hara, H.; Fujii, M; Oritani, H.; Koutoku, H.; Igarashi, S.; A novel class of inhibitors for human steroid 5alpha-reductase: Synthesis and biological evaluation of indole derivatives. II. Chem Pharm Bull 2000, 48, 3, 382.

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)	30840	5-Benzyloxyindole; benzyl 1H-indol-5-yl ether; 5-(benzyloxy)-1H-indole	1215-59-4	C₁₅H₁₃NO	详情	详情
(II)	12912	1-(Bromomethyl)benzene; Alpha-bromotoluene	100-39-0	C₇H₇Br	详情	详情
(III)	51281	benzyl 1-benzyl-1H-indol-5-yl ether; 1-benzyl-5-(benzyloxy)-1H-indole		C₂₂H₁₉NO	详情	详情
(IV)	51282	1-benzyl-1H-indol-5-ol		C₁₅H₁₃NO	详情	详情
(V)	51277	3-Chloro-4-fluorobenzonitrile	117482-84-5	C₇H₃ClFN	详情	详情
(VI)	51283	4-[(1-benzyl-1H-indol-5-yl)oxy]-3-chlorobenzonitrile		C₂₂H₁₅ClN₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Condensation of the magnesium iodide salt of 5-(benzyloxy)indole (I) with N-(benzyloxymethyl)-3,4-dibromomaleimide (II) provided the monoindolyl maleimide (III). Coupling of (III) with the benzyl-protected glucose (IV) via Mitsunobu reaction afforded the glycosylated indole (V). A second indolyl group was then introduced in (V) to give the bisindolylmaleimide (VI), which was oxidatively cyclized to the indolocarbazole (VII) using palladium bis(trifluoroacetate). Finally, hydrogenolysis of the benzyl protecting groups of (VII) over Pd/C furnished the title compound.

参考文献中间体

合成目标

【1】 Lineswala, J.P.; Kuffel, M.J.; Zhang, H.; Aytes, S.A.; Zembower, D.E.; Ames, M.M.; Indolocarbazole poisons of human topoisomerase I: Regioisomeric analogues of ED-110. Bioorg Med Chem Lett 1999, 9, 2, 145.

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)	30840	5-Benzyloxyindole; benzyl 1H-indol-5-yl ether; 5-(benzyloxy)-1H-indole	1215-59-4	C₁₅H₁₃NO	详情	详情
(II)	30841	1-[(benzyloxy)methyl]-3,4-dibromo-1H-pyrrole-2,5-dione		C₁₂H₉Br₂NO₃	详情	详情
(III)	30842	3-[5-(benzyloxy)-1H-indol-3-yl]-1-[(benzyloxy)methyl]-4-bromo-1H-pyrrole-2,5-dione		C₂₇H₂₁BrN₂O₄	详情	详情
(IV)	30843	(2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-ol		C₃₄H₃₆O₆	详情	详情
(V)	30844	1-[(benzyloxy)methyl]-3-(5-(benzyloxy)-1-[(2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]-1H-indol-3-yl)-4-bromo-1H-pyrrole-2,5-dione		C₆₁H₅₅BrN₂O₉	详情	详情
(VI)	30845	3-[5-(benzyloxy)-1H-indol-3-yl]-1-[(benzyloxy)methyl]-4-(5-(benzyloxy)-1-[(2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]-1H-indol-3-yl)-1H-pyrrole-2,5-dione		C₇₆H₆₇N₃O₁₀	详情	详情
(VII)	30846	3,9-bis(benzyloxy)-6-[(benzyloxy)methyl]-12-[(2R,3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]-12,13-dihydro-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione		C₇₆H₆₅N₃O₁₀	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The acylation of 5-(benzyloxy)indole (I) with ethyl chloroformate produced the N-(ethoxycarbonyl)indole (II), which was debenzylated by transfer hydrogenolysis with ammonium formate in the presence of Pd/C to afford the 5-hydroxyindole (III). Condensation of (III) with 3-chloro-4-fluorobenzonitrile (IV) produced the diaryl ether (V). Then, basic hydrolysis of the cyano and ethoxycarbonyl groups of (V) gave the benzoic acid derivative (VI). Finally, N-alkylation of the indole ring of (VI) with 4-phenoxybenzyl bromide (VII) furnished the title compound.

参考文献中间体

合成目标

【1】 Mase, T.; Inami, H.; Hara, H.; Fujii, M; Oritani, H.; Koutoku, H.; Igarashi, S.; A novel class of inhibitors for human steroid 5alpha-reductase: Synthesis and biological evaluation of indole derivatives. II. Chem Pharm Bull 2000, 48, 3, 382.

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)	30840	5-Benzyloxyindole; benzyl 1H-indol-5-yl ether; 5-(benzyloxy)-1H-indole	1215-59-4	C₁₅H₁₃NO	详情	详情
(II)	51275	ethyl 5-(benzyloxy)-1H-indole-1-carboxylate		C₁₈H₁₇NO₃	详情	详情
(III)	51276	ethyl 5-hydroxy-1H-indole-1-carboxylate		C₁₁H₁₁NO₃	详情	详情
(IV)	51277	3-Chloro-4-fluorobenzonitrile	117482-84-5	C₇H₃ClFN	详情	详情
(V)	51278	ethyl 5-(2-chloro-4-cyanophenoxy)-1H-indole-1-carboxylate		C₁₈H₁₃ClN₂O₃	详情	详情
(VI)	51279	3-chloro-4-(1H-indol-5-yloxy)benzoic acid		C₁₅H₁₀ClNO₃	详情	详情
(VII)	51280	1-(bromomethyl)-4-phenoxybenzene; 4-(bromomethyl)phenyl phenyl ether		C₁₃H₁₁BrO	详情	详情

Extended Information