1,6-hexanediamine; 6-aminohexylamine -Drug Synthesis Database

【结构式】

【分子编号】22344

【品名】1,6-hexanediamine; 6-aminohexylamine

【CA登记号】124-09-4

【分子式】C₆H₁₆N₂

【分子量】116.20652

【元素组成】C 62.02% H 13.88% N 24.11%

与该中间体有关的原料药合成路线共 5 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5

合成路线1

该中间体在本合成路线中的序号：(II)

By condensation of 5-chloronaphthalenesulfonyl chloride (I) with 1,6-diaminohexane (II) in refluxing dioxane

参考文献中间体

合成目标

【1】 Blancafort, P.; Hillier, K.; Serradell, M.N.; Castaner, J.; W-7. Drugs Fut 1982, 7, 11, 829.
【2】 Hidama, H.; Aoki, N. (Banyu Pharmaceutical Co., Ltd.); Omega-(Arylsulfonamido)-alkylamine. DE 2545496; FR 2321284; US 4069254 .

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)	37078	5-chloro-1-naphthalenesulfonyl chloride	6291-07-2	C₁₀H₆Cl₂O₂S	详情	详情
(II)	22344	1,6-hexanediamine; 6-aminohexylamine	124-09-4	C₆H₁₆N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Hexamethylenebisacetamide is prepared by reacting 1,6-hexanediamine (I) with two moles of acetic acid.

参考文献中间体

合成目标

【1】 Friend, C.; et al.; Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: Stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci USA 1976, 73, 3, 862.
【2】 Grimmelikhuysen, J.; Schroeder, A. (Unilever NV); Preparation of polyacetylalkylenediamines. BE 769655; DE 2133458; FR 2100320; GB 1335204 .
【3】 Eastland, G.; HMBA. Drugs Fut 1986, 11, 11, 933.

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)	22344	1,6-hexanediamine; 6-aminohexylamine	124-09-4	C₆H₁₆N₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(X)

Monoalkylation of 1,3-propanediamine (I) with 4-chlorobutanol (II) in refluxing n-BuOH afforded diaminoalcohol (III), which was protected as the bis-carbamate (IV) upon treatment with Boc2O. Subsequent reaction of (IV) with methanesulfonyl chloride and Et3N provided mesylate (V), and this was further treated with ethanolic ammonia to yield primary amine (VI). Condensation of amine (VI) with (methoxycarbonylmethyl) phenyl carbonate (VII) in refluxing toluene gave carbamate (VIII). Saponification of the methyl ester function of (VIII) then furnished carboxylic acid (IX). 1,6-Hexanediamine (X) was condensed with N,N'-bis(tert-butoxycarbonyl)-S-methylisothiourea (XI) to produce the (6-aminohexyl)guanidine derivative (XII). This was then coupled with carboxylic acid (IX) using DCC and HOBt. Finally, the N-Boc groups were deprotected with trifluoroacetic acid in CH2Cl2.

参考文献中间体

合成目标

【1】 Lebreton, L.; Annat, J.; Derrepas, P.; Dutartre, P.; Renaut, P.; Structure-immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 1. Structural modifications of the hydroxyglycine moiety. J Med Chem 1999, 42, 2, 277.

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)	19331	3-aminopropylamine; 1,3-propanediamine	109-76-2	C₃H₁₀N₂	详情	详情
(II)	22336	4-chloro-1-butanol	928-51-8	C₄H₉ClO	详情	详情
(III)	22337	4-[(3-aminopropyl)amino]-1-butanol		C₇H₁₈N₂O	详情	详情
(IV)	22338	tert-butyl 3-[(tert-butoxycarbonyl)amino]propyl(4-hydroxybutyl)carbamate		C₁₇H₃₄N₂O₅	详情	详情
(V)	22339	4-((tert-butoxycarbonyl)[3-[(tert-butoxycarbonyl)amino]propyl]amino)butyl methanesulfonate		C₁₈H₃₆N₂O₇S	详情	详情
(VI)	22340	tert-butyl 4-aminobutyl[3-[(tert-butoxycarbonyl)amino]propyl]carbamate		C₁₇H₃₅N₃O₄	详情	详情
(VII)	22341	methyl 2-[(phenoxycarbonyl)oxy]acetate		C₁₀H₁₀O₅	详情	详情
(VIII)	22342	methyl 9-(tert-butoxycarbonyl)-2,2-dimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oate		C₂₁H₃₉N₃O₈	详情	详情
(IX)	22343	9-(tert-butoxycarbonyl)-2,2-dimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oic acid		C₂₀H₃₇N₃O₈	详情	详情
(X)	22344	1,6-hexanediamine; 6-aminohexylamine	124-09-4	C₆H₁₆N₂	详情	详情
(XI)	22345	tert-butyl (E)-[(tert-butoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate		C₁₂H₂₂N₂O₄S	详情	详情
(XII)	22346	tert-butyl (Z)-[(6-aminohexyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate		C₁₇H₃₄N₄O₄	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

The title yohimbine dimer was prepared by coupling yohimbinic acid (I) with 1,6-hexanediamine (II) in the presence of dicyclohexylcarbodiimide and hydroxybenzotriazole, followed by conversion to the dihydrochloride salt.

参考文献中间体

合成目标

【1】 Miller, D.D.; Lalchandani, S.; Feller, D.R.; Sun, G.; Lei, L.; Zheng, W.; Yohimbine dimers exhibiting binding selectivities for human alpha2a - versus alpha2b adrenergic receptors. Bioorg Med Chem Lett 2000, 10, 7, 627.

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)	42597	(1R,2S,4aR,13bS,14aS)-2-hydroxy-1,2,3,4,4a,5,7,8,13,13b,14,14a-dodecahydroindolo[2',3':3,4]pyrido[1,2-b]isoquinoline-1-carboxylic acid		C₂₀H₂₄N₂O₃	详情	详情
(II)	22344	1,6-hexanediamine; 6-aminohexylamine	124-09-4	C₆H₁₆N₂	详情	详情

合成路线5

该中间体在本合成路线中的序号：(IV)

Condensation of amine (I) with diphenyl cyanocarbonimidate (II) affords isourea (III), which is then converted into cyanoguanidine (V) by coupling with diamine (IV) in CH2Cl2. The final step for the synthesis of the desired product is the reaction of the primary amine group of (V) with the active ester (VI) obtained by activation of calvatic acid (VII) with N-hydroxysuccinimide (N-HOSu) and N,N'-dicyclohexyl-carbodiimide (DCC) in THF.

参考文献中间体

合成目标

【1】 Hirschfeld, J.; et al.; Iodoaminopotentidine and related compounds: A new class of ligands with high affinity and selectivity for the histamine H2 receptor. J Med Chem 1992, 35, 12, 2231.
【2】 Sorba, G.; Dubini, F.; Brenciaglia, M.I.; Bertinaria, M.; Scaltrito, M.M.; Di Stilo, A.; Gasco, A.; Anti-Helicobacter pylori agents endowed with H2-antagonist properties. Bioorg Med Chem Lett 2001, 11, 3, 403.

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)	16105	3-[3-(piperidinomethyl)phenoxy]-1-propanamine; 3-[3-(piperidinomethyl)phenoxy]propylamine		C₁₅H₂₄N₂O	详情	详情
(II)	25868	1-[(cyanoimino)(phenoxy)methoxy]benzene	107-37-9	C₁₄H₁₀N₂O₂	详情	详情
(III)	48290	1-[3-(3-[[(cyanoimino)(phenoxy)methyl]amino]propoxy)benzyl]piperidine		C₂₃H₂₈N₄O₂	详情	详情
(IV)	22344	1,6-hexanediamine; 6-aminohexylamine	124-09-4	C₆H₁₆N₂	详情	详情
(V)	48291	N-(6-aminohexyl)-N''-cyano-N'-[3-[3-(1-piperidinylmethyl)phenoxy]propyl]guanidine		C₂₃H₃₈N₆O	详情	详情
(VI)	48292	2-cyano-1-(4-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]phenyl)-1-oxidodiazen-1-ium		C₁₂H₈N₄O₅	详情	详情
(VII)	48293	(E)-1-(4-carboxyphenyl)-2-cyano-1-oxidodiazen-1-ium		C₈H₅N₃O₃	详情	详情

Extended Information