N-(3-aminopropyl)-N-[4-[(3-aminopropyl)amino]butyl]amine; N(1),N(4)-bis(3-aminopropyl)-1,4-butanediamine -Drug Synthesis Database

【结构式】

【分子编号】46326

【品名】N-(3-aminopropyl)-N-[4-[(3-aminopropyl)amino]butyl]amine; N(1),N(4)-bis(3-aminopropyl)-1,4-butanediamine

【CA登记号】

【分子式】C₁₀H₂₆N₄

【分子量】202.3434

【元素组成】C 59.36% H 12.95% N 27.69%

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)

Di-Boc-protected L-lysine p-nitrophenyl active ester (I) was coupled to spermine (II), yielding the primary amide (III) along with some by-products. The crude reaction mixture was fully protected using an excess of di-tert-butyl dicarbonate, and the desired compound (IV) was then isolated by column chromatography. Finally, the Boc-protecting groups of (IV) were removed by acidic treatment to provide the title spermine lysinamide.

参考文献中间体

合成目标

【1】 Burns, M.R.; O'Day, C.L.; Bergstrom, D.E.; Webb, H.K.; Vermeulin, N.M.J. (Oridigm Corp.); Novel polyamine analogues as therapeutic and diagnostic agents. EP 1085011 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	46325	4-nitrophenyl (2S)-2,6-bis[(tert-butoxycarbonyl)amino]hexanoate	C₂₂H₃₃N₃O₈	详情	详情
(II)	46326	N-(3-aminopropyl)-N-[4-[(3-aminopropyl)amino]butyl]amine; N(1),N(4)-bis(3-aminopropyl)-1,4-butanediamine	C₁₀H₂₆N₄	详情	详情
(III)	46327	tert-butyl (5S)-6-[[3-([4-[(3-aminopropyl)amino]butyl]amino)propyl]amino]-5-[(tert-butoxycarbonyl)amino]-6-oxohexylcarbamate	C₂₆H₅₄N₆O₅	详情	详情
(IV)	46328	tert-butyl 3-([(2S)-2,6-bis[(tert-butoxycarbonyl)amino]hexanoyl]amino)propyl[4-((tert-butoxycarbonyl)[3-[(tert-butoxycarbonyl)amino]propyl]amino)butyl]carbamate	C₄₁H₇₈N₆O₁₁	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The N-hydroxysuccinimide ester of di-carbobenzyloxy-L-lysine (IV) was coupled to spermine (II), yielding amide (V). The N- carbobenzyloxy groups were then deprotected by catalytic hydrogenolysis in the presence of Pearlman’s catalyst.

参考文献中间体

合成目标

【1】 Cai, F.; Carlson, C.L.; Vanderwerf, S.M.; Devens, B.H.; Webb, H.K.; O'Day, C.L.; Burns, M.R.; Weeks, R.S.; Novel lysine-spermine conjugate inhibits polyamine transport and inhibits cell growth when given with DFMO. Exp Cell Res 2000, 261, 1, 293.
【2】 Burns, M.R.; et al.; Amino acid/spermine conjugates: Polyamine amides as potent spermidine uptake inhibitors. J Med Chem 2001, 44, 22, 3632.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	52059	benzyl (1S)-5-[[(benzyloxy)carbonyl]amino]-1-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]pentylcarbamate	C₂₆H₂₉N₃O₈	详情	详情
(II)	46326	N-(3-aminopropyl)-N-[4-[(3-aminopropyl)amino]butyl]amine; N(1),N(4)-bis(3-aminopropyl)-1,4-butanediamine	C₁₀H₂₆N₄	详情	详情
(III)	52305		C₃₂H₅₀N₆O₅	详情	详情

合成路线3

该中间体在本合成路线中的序号：(V)

Acylation of the primary amino groups of spermine (V) by the N acyl thiazolide (VI) furnishes diamide (VII). This is further coupled with acid chloride (IV) producing tetraamide (VIII). Finally, deprotection of the O-benzyl groups under acidic conditions gives rise to the title compound.

参考文献中间体

合成目标

【1】 Xu, J.; et al.; Synthesis and initial evaluation for in vivo chelation of Pu(IV) of a mixed octadentate spermine-based ligand containing 4-carbamoyl-3-hydroxy-1-methyl-2(1H)-pyridinone and 6-carbamoyl-1-hydroxy-2(1H)-pyridinone. J Med Chem 2002, 45, 18, 3963.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IV)	61993	1-(benzyloxy)-6-oxo-1,6-dihydro-2-pyridinecarbonyl chloride	C₁₃H₁₀ClNO₃	详情	详情
(V)	46326	N-(3-aminopropyl)-N-[4-[(3-aminopropyl)amino]butyl]amine; N(1),N(4)-bis(3-aminopropyl)-1,4-butanediamine	C₁₀H₂₆N₄	详情	详情
(VI)	48345	3-(benzyloxy)-1-methyl-4-[(2-thioxo-1,3-thiazolidin-3-yl)carbonyl]-2(1H)-pyridinone	C₁₇H₁₆N₂O₃S₂	详情	详情
(VII)	61994	3-(benzyloxy)-N-{3-[(4-{[3-({[3-(benzyloxy)-1-methyl-2-oxo-1,2-dihydro-4-pyridinyl]carbonyl}amino)propyl]amino}butyl)amino]propyl}-1-methyl-2-oxo-1,2-dihydro-4-pyridinecarboxamide	C₃₈H₄₈N₆O₆	详情	详情
(VIII)	61995	1-(benzyloxy)-N-[3-({[3-(benzyloxy)-1-methyl-2-oxo-1,2-dihydro-4-pyridinyl]carbonyl}amino)propyl]-N-[4-([3-({[3-(benzyloxy)-1-methyl-2-oxo-1,2-dihydro-4-pyridinyl]carbonyl}amino)propyl]{[1-(benzyloxy)-6-oxo-1,6-dihydro-2-pyridinyl]carbonyl}amino)but	C₆₄H₆₆N₈O₁₂	详情	详情

Extended Information