1,4,8,11-Tetraazaundecane; 3,7-Diaza-1,9-nonanediamine; N,N'-Bis(2-aminoethyl)-1,3-propanediamine; N,N[-Bis(2-aminoethyl)-1,3-propanediamine -Drug Synthesis Database

【结构式】

【分子编号】53968

【品名】1,4,8,11-Tetraazaundecane; 3,7-Diaza-1,9-nonanediamine; N,N'-Bis(2-aminoethyl)-1,3-propanediamine; N,N[-Bis(2-aminoethyl)-1,3-propanediamine

【CA登记号】4741-99-5

【分子式】C₇H₂₀N₄

【分子量】160.26276

【元素组成】C 52.46% H 12.58% N 34.96%

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：(XXIII)

A different protection strategy involves masking the ring nitrogens as amide groups. Methyl acrylate (XVII) is reacted with neat ethylenediamine (XVIII) to yield the aminopropionamide derivative (XIX), which is then cyclized with dimethyl malonate (XX), producing the trioxocyclam (XXI). After condensation of (XXI) with p-dibromoxylene (IIIa), the resulting hexaoxo bis-cyclam (XXII) is reduced to the title compound employing borane-dimethyl sulfide complex in refluxing THF (10). Alternatively, protection of the linear tetraamine (XXIII) with pyruvic aldehyde (XXIV) generates the tricyclic bisaminal (XXV) along with its minor isomer (XXVI). The crude mixture of bis-aminals (XXV) and (XXVI) is then cyclized to (XXVIII) with 1,3-dibromopropane (XXVII) and K2CO3. After condensation of (XXVIII) with dibromide (IIIa), the resulting bis-ammonium dimer (XXIX) is hydrolyzed to the title compound upon heating with 3M NaOH (11). Scheme 3.

参考文献中间体

合成目标

【10】 Achmatowicz, M., Hegedus, L.S. Direct synthesis of 1,1’-[1,4-phenylenebis(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane octahydrochloride (AMD 3100) without the use of protecting groups. J Org Chem 2003, 68(16): 6435-6.
【11】 Boschetti, F., Denat, F., Espinosa, E., Tabard, A., Dory, Y., Guilard, R. Regioselective N-functionalization of tetraazacycloalkanes. J Org Chem 2005, 70(18): 7042-53.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IIIa)	18697	1,4-bis(bromomethyl)benzene	623-24-5	C₈H₈Br₂	详情	详情
(XVII)	14156	methyl acrylate	96-33-3	C₄H₆O₂	详情	详情
(XVIII)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情
(XIX)	65221			C₇H₁₈N₄O	详情	详情
(XX)	19373	dimethyl malonate；Methyl malonate;Propanedioic acid dimethyl ester	108-59-8	C₅H₈O₄	详情	详情
(XXI)	65222			C₁₀H₁₈N₄O₃	详情	详情
(XXII)	65223			C₂₈H₄₂N₈O₆	详情	详情
(XXIII)	53968	1,4,8,11-Tetraazaundecane; 3,7-Diaza-1,9-nonanediamine; N,N'-Bis(2-aminoethyl)-1,3-propanediamine; N,N[-Bis(2-aminoethyl)-1,3-propanediamine	4741-99-5	C₇H₂₀N₄	详情	详情
(XXIV)	25598	2-oxopropanal	78-98-8	C₃H₄O₂	详情	详情
(XXV)	65224			C₁₀H₂₀N₄	详情	详情
(XXVI)	65225			C₁₀H₂₀N₄	详情	详情
(XXVII)	12581	1,3-Dibromopropane	109-64-8	C₃H₆Br₂	详情	详情
(XXVIII)	65526			C₂₆H₃₇O₇P	详情	详情
(XXIX)	65227			C₃₄H₅₄Br₂N₈	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

By condensation of 1,8-naphthalic anhydride (I) wih N,N’-bis(2-aminoethyl)propane-1,2-diamine (II) in refluxing dioxane, or in hot NMM.

参考文献中间体

合成目标

【1】 Brana, M.F.; et al.; Bis-naphthalimides 3: Synthesis and antitumor activity of N,N'-bis[2-(1,8-naphthalimido)-ethyl]alkanediamines. Anti-Cancer Drug Des 1996, 11, 4, 297.
【2】 Keilhauer, G.; Romerdahl, C.; Brana, M.F.; Qian, X.-D.; Bousquet, P.; Castellano Berlanga, J.M.; Moran Moset, M.; Perez De Vega, M.J. (BASF AG); New bis-naphthalimides for the treatment of cancer. EP 0714387; JP 1997501662; US 5616589; WO 9505365 .
【3】 Koser, S.; Viergutz, W. (BASF AG); Method for producing aromatic bisimides. DE 19720803; WO 9852924 .

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)	16982	1H,3H-benzo[de]isochromene-1,3-dione; 1,8-Naphthalic Anhydride	81-84-5	C₁₂H₆O₃	详情	详情
(II)	53968	1,4,8,11-Tetraazaundecane; 3,7-Diaza-1,9-nonanediamine; N,N'-Bis(2-aminoethyl)-1,3-propanediamine; N,N[-Bis(2-aminoethyl)-1,3-propanediamine	4741-99-5	C₇H₂₀N₄	详情	详情

Extended Information