1,8-octanediamine; 8-aminooctylamine -Drug Synthesis Database

【结构式】

【分子编号】20965

【品名】1,8-octanediamine; 8-aminooctylamine

【CA登记号】373-44-4

【分子式】C₈H₂₀N₂

【分子量】144.26028

【元素组成】C 66.61% H 13.97% N 19.42%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

N-(Benzyloxycarbonyl)-6-aminocaproic acid (I) is reacted with 1,8-octanediamine (II) to give amide (III). The protecting group can be removed either by hydrogenolysis or by gaseous HBr affording (IV), which is reduced with borane-methyl sulfide complex to yield N,N'-bis(6-aminohexyl)-1,8-octanediamine (V). Condensation of (V) with 2-methoxybenzaldehyde and subsequent reduction of the intermediate Schiff base gives methoctramine. However, methoctramine can be prepared more conveniently by transforming (IV) to (VI) followed by reduction of amide groups with borane.

参考文献中间体

合成目标

【1】 Melchiorre, C.; Minarini, A.; Quaglia, W.; Tumiatti, V.; METHOCTRAMINE. Drugs Fut 1989, 14, 7, 628.
【2】 Quaglia, W.; Melchiorre, C.; Cassinelli, A.; Differential blockade of muscarinic receptor subtypes by polymethylene tetraamines. Novel class of selective antagonists of cardiac M2 muscarinic receptors. J Med Chem 1987, 30, 1, 201.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	12568	2-Methoxybenzaldehyde; o-Methoxybenzaldehyde	135-02-4	C₈H₈O₂	详情	详情
(I)	20964	6-[[(benzyloxy)carbonyl]amino]hexanoic acid	1947-00-8	C₁₄H₁₉NO₄	详情	详情
(II)	20965	1,8-octanediamine; 8-aminooctylamine	373-44-4	C₈H₂₀N₂	详情	详情
(III)	20966	benzyl 6,17,24-trioxo-26-phenyl-25-oxa-7,16,23-triazahexacos-1-ylcarbamate		C₃₆H₅₄N₄O₆	详情	详情
(IV)	20967	6-amino-N-[8-[(6-aminohexanoyl)amino]octyl]hexanamide		C₂₀H₄₂N₄O₂	详情	详情
(V)	20968	N(1),N(8)-bis(6-aminohexyl)-1,8-octanediamine; N-(6-aminohexyl)-N-[8-[(6-aminohexyl)amino]octyl]amine		C₂₀H₄₆N₄	详情	详情
(VI)	20969	6-[(2-methoxybenzyl)amino]-N-[8-([6-[(2-methoxybenzyl)amino]hexanoyl]amino)octyl]hexanamide		C₃₆H₅₈N₄O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

Addition of 4-chlorophenylmagnesium bromide (II) to arecoline (I) in Et2O at -10 C afforded the corresponding 4-arylpiperidine-3-carboxylate as a mixture of trans (III) and cis (IV) isomers. After chromatographic isolation of the racemic cis isomer (IV), resolution employing dibenzoyl-D-tartaric acid furnished the dextro enantiomer (cis)(+)-(IV). Its epimerization in the presence of NaOMe produced a 1:5.6 mixture of cis/trans isomers, from which the major compound (-)-(trans)(III) was isolated by flash chromatography. Acid hydrolysis of its methyl ester group provided carboxylic acid (V), that was further converted to acid chloride (VI) using oxalyl chloride (1,2). Finally, coupling of (VI) with 1,8-octanediamine (VII) gave the title diamide.

参考文献中间体

合成目标

【1】 Tamiz, A.P.; Johnson, K.M.; Wang, C.Z.; Kozikowski, A.P.; Zhang, J.; Zhang, M.; Application of the bivalent ligand approach to the design of novel dimeric serotonin reuptake inhibitors. J Am Chem Soc 2000, 122, 22, 5393.
【2】 Tamiz, A.P.; Araldi, G.L.; Kozikowski, A.P. (Georgetown University); Monomeric and dimeric heterocycles, and therapeutic uses thereof. WO 0020390 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(rac)-(III)	41630	(rac)-methyl (3S,4R)-4-(4-chlorophenyl)-1-methyl-3-piperidinecarboxylate	n/a	C₁₄H₁₈ClNO₂	详情	详情
(rac)-(IV)	41631	(rac)-methyl (3R,4R)-4-(4-chlorophenyl)-1-methyl-3-piperidinecarboxylate		C₁₄H₁₈ClNO₂	详情	详情
(+)-(IV)	41632	(+)-methyl (3R,4R)-4-(4-chlorophenyl)-1-methyl-3-piperidinecarboxylate		C₁₄H₁₈ClNO₂	详情	详情
(-)-(III)	41633	(-)-methyl (3S,4R)-4-(4-chlorophenyl)-1-methyl-3-piperidinecarboxylate		C₁₄H₁₈ClNO₂	详情	详情
(I)	25127	bromo(4-chlorophenyl)magnesium	873-77-8	C₆H₄BrClMg	详情	详情
(I)	38648	methyl 1-methyl-1,2,5,6-tetrahydro-3-pyridinecarboxylate		C₈H₁₃NO₂	详情	详情
(V)	41634	(3S,4R)-4-(4-chlorophenyl)-1-methyl-3-piperidinecarboxylic acid		C₁₃H₁₆ClNO₂	详情	详情
(VI)	41635	(3S,4R)-4-(4-chlorophenyl)-1-methyl-3-piperidinecarbonyl chloride		C₁₃H₁₅Cl₂NO	详情	详情
(VII)	20965	1,8-octanediamine; 8-aminooctylamine	373-44-4	C₈H₂₀N₂	详情	详情

Extended Information