4-(aminomethyl)aniline; 4-aminobenzylamine -Drug Synthesis Database

【结构式】

【分子编号】35548

【品名】4-(aminomethyl)aniline; 4-aminobenzylamine

【CA登记号】4403-71-8

【分子式】C₇H₁₀N₂

【分子量】122.16988

【元素组成】C 68.82% H 8.25% N 22.93%

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：(V)

The known indole-2-carboxylate intermediate (I) was protected as the N-benzenesulfonyl derivative (II) using benzenesulfonyl chloride and NaH, and the tert-butyl ester group of (II) was subsequently cleaved by means of formic acid. The resulting carboxylic acid (III) was activated as the 2-pyridyl thioester (IV) upon treatment with 2,2'-dipyridyl disulfide and triphenylphosphine. Selective protection of 4-aminobenzyl amine (V) with Boc2O produced the amino carbamate (VI). This was coupled with pyridyl thioester (IV) in refluxing THF to yield amide (VII). Subsequent removal of the N-Boc group of (VII) with trifluoroacetic acid afforded the free amino derivative (VIII), which was converted to the required urea (IX) upon treatment with trimethylsilyl isocyanate. Further hydrolysis of the benzenesulfonyl group of (IX) with ethanolic NaOH furnished the deprotected indole (X).

参考文献中间体

合成目标

【1】 Conti, N.; Di Fabio, R.; De Magistris, E.; Feriani, A. (Glaxo Wellcome plc); Indole derivs. as EAA antagonists. EP 0813524; JP 1999501041; US 5919811; WO 9627588 .

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)	32148	ethyl 3-[(E)-3-(tert-butoxy)-3-oxo-1-propenyl]-4,6-dichloro-1H-indole-2-carboxylate		C₁₈H₁₉Cl₂NO₄	详情	详情
(II)	35545	ethyl 3-[(E)-3-(tert-butoxy)-3-oxo-1-propenyl]-4,6-dichloro-1-(phenylsulfonyl)-1H-indole-2-carboxylate		C₂₄H₂₃Cl₂NO₆S	详情	详情
(III)	35546	(E)-3-[4,6-dichloro-2-(ethoxycarbonyl)-1-(phenylsulfonyl)-1H-indol-3-yl]-2-propenoic acid		C₂₀H₁₅Cl₂NO₆S	详情	详情
(IV)	35547	ethyl 4,6-dichloro-3-[(E)-3-oxo-3-(2-pyridinylsulfanyl)-1-propenyl]-1-(phenylsulfonyl)-1H-indole-2-carboxylate		C₂₅H₁₈Cl₂N₂O₅S₂	详情	详情
(V)	35548	4-(aminomethyl)aniline; 4-aminobenzylamine	4403-71-8	C₇H₁₀N₂	详情	详情
(VI)	35549	tert-butyl 4-aminobenzylcarbamate		C₁₂H₁₈N₂O₂	详情	详情
(VII)	35550	ethyl 3-[(E)-3-(4-[[(tert-butoxycarbonyl)amino]methyl]anilino)-3-oxo-1-propenyl]-4,6-dichloro-1-(phenylsulfonyl)-1H-indole-2-carboxylate		C₃₂H₃₁Cl₂N₃O₇S	详情	详情
(VIII)	35551	ethyl 3-[(E)-3-[4-(aminomethyl)anilino]-3-oxo-1-propenyl]-4,6-dichloro-1-(phenylsulfonyl)-1H-indole-2-carboxylate		C₂₇H₂₃Cl₂N₃O₅S	详情	详情
(IX)	35552	ethyl 3-[(E)-3-(4-[[(aminocarbonyl)amino]methyl]anilino)-3-oxo-1-propenyl]-4,6-dichloro-1-(phenylsulfonyl)-1H-indole-2-carboxylate		C₂₈H₂₄Cl₂N₄O₆S	详情	详情
(X)	35553	ethyl 3-[(E)-3-(4-[[(aminocarbonyl)amino]methyl]anilino)-3-oxo-1-propenyl]-4,6-dichloro-1H-indole-2-carboxylate		C₂₂H₂₀Cl₂N₄O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

In a more direct route, 4-aminobenzyl amine (V) was treated with trimethylsilyl isocyanate to yield amino urea (XVI). This was subsequently coupled with pyridyl thioester (XIII) to furnish the previously described intermediate (X).

参考文献中间体

合成目标

【1】 Conti, N.; Di Fabio, R.; De Magistris, E.; Feriani, A. (Glaxo Wellcome plc); Indole derivs. as EAA antagonists. EP 0813524; JP 1999501041; US 5919811; WO 9627588 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	35548	4-(aminomethyl)aniline; 4-aminobenzylamine	4403-71-8	C₇H₁₀N₂	详情	详情
(X)	35553	ethyl 3-[(E)-3-(4-[[(aminocarbonyl)amino]methyl]anilino)-3-oxo-1-propenyl]-4,6-dichloro-1H-indole-2-carboxylate		C₂₂H₂₀Cl₂N₄O₄	详情	详情
(XIII)	32150	ethyl 4,6-dichloro-3-[(E)-3-oxo-3-(2-pyridinylsulfanyl)-1-propenyl]-1H-indole-2-carboxylate		C₁₉H₁₄Cl₂N₂O₃S	详情	详情
(XVI)	35556	N-(4-aminobenzyl)urea		C₈H₁₁N₃O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

4-Aminobenzylamine (I) was protected as the tert-butyl carbamate (II) upon treatment with Boc2O. Heating of (II) with cyanamide afforded guanidine (III). The Boc protecting group of (III) was then removed by means of trifluoroacetic acid to furnish 4-guanidinobenzylamine (IV). 4-Boc-piperazine-1-carbonyl chloride (VI) (obtained by treatment of N-Boc piperazine (V) with triphosgene) was condensed with amine (IV), yielding urea (VII). The N-Boc group of (VII) was then deprotected with trifluoroacetic acid to give (VIII) (1). Dianhydromannitol (X) was converted to bischloroformate (XI) by treatment with phosgene. Then condensation of (XI) with piperazine (VIII) provided the title biscarbamate.

参考文献中间体

合成目标

【2】 Gangloff, A.R.; Kuo, E.Y.-L.; Dener, J.M.; Rice, K.D. (Axys Pharmaceuticals, Inc.); Compsns. and methods for treating mast-cell inflammatory condition. US 6022969; WO 9609297 .
【1】 Putnam, D.; Dener, J.M.; Gangloff, A.R.; Wong, M.; Rice, K.D.; Wng, V.R.; Young, W.B.; Simpson, P.J.; Kuo, E.Y.-L.; Cregar, L.; Newcomb, W.S.; Dibasic inhibitors of human mast cell tryptase. Part 2: Structure-activity relationships and requirements for potent activity. Bioorg Med Chem Lett 2000, 10, 20, 2361.

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)	35548	4-(aminomethyl)aniline; 4-aminobenzylamine	4403-71-8	C₇H₁₀N₂	详情	详情
(II)	35549	tert-butyl 4-aminobenzylcarbamate		C₁₂H₁₈N₂O₂	详情	详情
(III)	45504	tert-butyl 4-[[amino(imino)methyl]amino]benzylcarbamate		C₁₃H₂₀N₄O₂	详情	详情
(IV)	45505	N-[4-(aminomethyl)phenyl]guanidine		C₈H₁₂N₄	详情	详情
(V)	13225	N-tert-Butoxycarbonyl piperazine; tert-butyl 1-piperazinecarboxylate;tert-butyl piperazine-1-carboxylate	143238-38-4	C₉H₁₈N₂O₂	详情	详情
(VI)	28999	tert-butyl 4-(chlorocarbonyl)-1-piperazinecarboxylate		C₁₀H₁₇ClN₂O₃	详情	详情
(VII)	45507	N-(4-[[amino(imino)methyl]amino]benzyl)-1-piperazinecarboxamide		C₁₃H₂₀N₆O	详情	详情
(VIII)	45506	tert-butyl 4-[[(4-[[amino(imino)methyl]amino]benzyl)amino]carbonyl]-1-piperazinecarboxylate		C₁₈H₂₈N₆O₃	详情	详情
(IX)	45508	(3R,3aR,6R,6aR)hexahydrofuro[3,2-b]furan-3,6-diol	3261-62-9	C₆H₁₀O₄	详情	详情
(X)	45509	(3R,3aS,6R,6aS)-3,6-bis[(chlorocarbonyl)oxy]hexahydrofuro[3,2-b]furan	67-73-2	C₈H₈Cl₂O₆	详情	详情

Extended Information