1,4-butanediamine; 4-aminobutylamine -Drug Synthesis Database

【结构式】

【分子编号】42070

【品名】1,4-butanediamine; 4-aminobutylamine

【CA登记号】110-60-1

【分子式】C₄H₁₂N₂

【分子量】88.15276

【元素组成】C 54.5% H 13.72% N 31.78%

与该中间体有关的原料药合成路线共 6 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6

合成路线1

该中间体在本合成路线中的序号：(III)

The reaction of S-methylisothiourea (I) with Boc2O by means of NaHCO3 gives the N-Boc protected isothiourea (II), which is condensed with 1,4-butanediamine (III) in hot THF to yield the guanidine derivative (IV). The acylation of the amino group of (IV) with 3,4-dimethoxycinnamoyl chloride (V) with THF/DMF affords the corresponding amide (VI), which is deprotected with TFA to provide N-(4-guanidinobutyl)-3,4-dimethoxycinnamamide (VII). Finally, the guanidino group of (VII) is alkylated with 3-methyl-2-butenyl bromide (VIII) catalyzed by DMAP in THF to provide the target, caracasanamide.

参考文献中间体

合成目标

【1】 Delle Monache, G.; Delle Monache, F.; Botta, B.; Bonnevaux Castillo, S.; Espinal, R.; De Luca, C.; Carmignani, M. (Consiglio Nazionale delle Ricerche); Guanidine derivs. having hypotensive activity, compsn. containing them, and process for obtaining them. EP 0330629; JP 1990003661; US 5059624 .

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)	10272	[[Amino(imino)methyl]sulfanyl]methane	2986-19-8	C₂H₆N₂S	详情	详情
(II)	22345	tert-butyl (E)-[(tert-butoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate		C₁₂H₂₂N₂O₄S	详情	详情
(III)	42070	1,4-butanediamine; 4-aminobutylamine	110-60-1	C₄H₁₂N₂	详情	详情
(IV)	53109	tert-butyl (Z)-[(4-aminobutyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate	n/a	C₁₅H₃₀N₄O₄	详情	详情
(V)	33601	(E)-3-(3,4-dimethoxyphenyl)-2-propenoyl chloride		C₁₁H₁₁ClO₃	详情	详情
(VI)	53110	tert-butyl (Z)-[(tert-butoxycarbonyl)amino][(4-{[(E)-3-(3,4-dimethoxyphenyl)-2-propenoyl]amino}butyl)amino]methylidenecarbamate	n/a	C₂₆H₄₀N₄O₇	详情	详情
(VII)	53111	(E)-N-(4-{[amino(imino)methyl]amino}butyl)-3-(3,4-dimethoxyphenyl)-2-propenamide	n/a	C₁₆H₂₄N₄O₃	详情	详情
(VIII)	12989	4-Bromo-2-methyl-2-butene; 1-Bromo-3-methyl-2-butene	870-63-3	C₅H₉Br	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The chlorination of 5-(hydroxymethyl)imidazo[1,2-a]pyridine (I) with SOCl2 in dichloromethane gives the corresponding chloromethyl derivative (II), which is condensed with 1,4-diaminobutane (III) in refluxing acetonitrile to yield 5-(4-aminobutylaminomethyl)imidazo[1,2-a]pyridine (IV). The sulfonation of (IV) with N-phenyltrifluoromethylsulfonimide (V) and TEA in acetonitrile affords the sulfonamide (VI), which is protected with Boc2O in ethanol to provide the carbamate (VII). The acylation of (VII) with trichloroacetyl chloride and DMAP in refluxing chloroform gives the 3-trichloroacetyl derivative (VIII), which is finally cyclized by means of Tms-I and NaHCO3 in chloroform.

参考文献中间体

合成目标

【1】 Ikemoto, T.; et al.; A practical synthesis of the chronic renal disease agent, 4,5-dihydro-3H-1,4,8b-triazaacenaphthylen-3-one derivatives, using regioselective chlorination of ethyl 5-methylimidazo[1,2-a]pyridine-3-carboxy with N-chlorosuccinimide. Tetrahedron 2000, 56, 40, 7915.
【2】 Takatani, M.; Shibouta, Y.; Tomimatsu, K.; Kawamoto, T. (Takeda Chemical Industries, Ltd.); Tricyclic cpds., their production and use. EP 0771319; JP 1996081467; WO 9602542 .

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)	42068	imidazo[1,2-a]pyridin-5-ylmethanol		C₈H₈N₂O	详情	详情
(II)	42069	5-(chloromethyl)imidazo[1,2-a]pyridine		C₈H₇ClN₂	详情	详情
(III)	42070	1,4-butanediamine; 4-aminobutylamine	110-60-1	C₄H₁₂N₂	详情	详情
(IV)	42071	N(1)-(imidazo[1,2-a]pyridin-5-ylmethyl)-1,4-butanediamine; N-(4-aminobutyl)-N-(imidazo[1,2-a]pyridin-5-ylmethyl)amine		C₁₂H₁₈N₄	详情	详情
(V)	17573	N-Phenyltrifluoromethanesulfonimide; Trifluoro-N-phenyl-N-[(trifluoromethyl)sulfonyl]methanesulfonamide	37595-74-7	C₈H₅F₆NO₄S₂	详情	详情
(VI)	42072	trifluoro-N-[4-[(imidazo[1,2-a]pyridin-5-ylmethyl)amino]butyl]methanesulfonamide		C₁₃H₁₇F₃N₄O₂S	详情	详情
(VII)	42073	tert-butyl imidazo[1,2-a]pyridin-5-ylmethyl(4-[[(trifluoromethyl)sulfonyl]amino]butyl)carbamate		C₁₈H₂₅F₃N₄O₄S	详情	详情
(VIII)	42074	tert-butyl [3-(2,2,2-trichloroacetyl)imidazo[1,2-a]pyridin-5-yl]methyl(4-[[(trifluoromethyl)sulfonyl]amino]butyl)carbamate		C₂₀H₂₄Cl₃F₃N₄O₅S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The mono-Boc-protected diamine (II) was obtained by reaction of 1,4-diaminobutane (I) with Boc2O. Reductive alkylation of (II) to the benzylic amine (V) was carried out in a two-step procedure consisting in condensation of amine (II) with the formyl boronic ester (III) in the presence of molecular sieves, followed by reduction of the resultant imine (IV) with NaBH4. The N-Boc protecting group of (V) was then removed by acidic treatment, yielding diamine (VI). The title boronic acid was finally obtained by boronate ester exchange in (VI) with phenylboronic acid in a two-phase system.

参考文献中间体

合成目标

【1】 Martin, B.; et al.; N'-Benzylpolyamines as vectors of boron and fluorine for cancer therapy and imaging: Synthesis and biological evaluation. J Med Chem 2001, 44, 22, 3653.

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)	42070	1,4-butanediamine; 4-aminobutylamine	110-60-1	C₄H₁₂N₂	详情	详情
(II)	53376	N-(4-Aminobutyl)carbamic acid tert-butyl ester; N-(tert-Butoxycarbonyl)-1,4-diaminobutane	68076-36-8	C₉H₂₀N₂O₂	详情	详情
(III)	53377	4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzaldehyde	128376-65-8	C₁₂H₁₅BO₃	详情	详情
(IV)	53378	tert-butyl 4-({(E)-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)phenyl]methylidene}amino)butylcarbamate	n/a	C₂₁H₃₃BN₂O₄	详情	详情
(V)	53379	tert-butyl 4-{[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzyl]amino}butylcarbamate	n/a	C₂₁H₃₅BN₂O₄	详情	详情
(VI)	53380	N-(4-aminobutyl)-N-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzyl]amine; N~1~-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)benzyl]-1,4-butanediamine	n/a	C₁₆H₂₇BN₂O₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(I)

Reductive condensation of 1,4-butanediamine (I) with glyoxylic acid (II) affords 3,8-diazaoctanoic acid (III). Subsequent acylation of diamino acid (III) with 2,3-diacetoxybenzoyl chloride (IV) provides diamide (V). After activation of (V) as the corresponding mixed anhydride with either methyl or isobutyl chloroformate, condensation with ampicillin (VI) yields the title compound.

参考文献中间体

合成目标

【1】 RF-2691A. Drug Data Rep 1995, 17, 9, 867.
【2】 Berg, A.; Heinisch, L.; Mollmann, U.; Wittmann, S.; Scherlitz-Hofmann, I.; Stoiber, T. (Grunenthal GmbH); Catecholate beta-lactam conjugates, method for producing the same and the use thereof. DE 10111160; WO 0270016 .

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)	42070	1,4-butanediamine; 4-aminobutylamine	110-60-1	C₄H₁₂N₂	详情	详情
(II)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(III)	58505	2-[(4-aminobutyl)amino]acetic acid		C₆H₁₄N₂O₂	详情	详情
(IV)	58506	2-(acetyloxy)-3-(chlorocarbonyl)phenyl acetate		C₁₁H₉ClO₅	详情	详情
(V)	58507	2-[[2,3-bis(acetyloxy)benzoyl](4-{[2,3-bis(acetyloxy)benzoyl]amino}butyl)amino]acetic acid		C₂₈H₃₀N₂O₁₂	详情	详情
(VI)	31107	(2S,5R,6R)-6-[[(2R)-2-amino-2-phenylethanoyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid	69-53-4	C₁₆H₁₉N₃O₄S	详情	详情

合成路线5

该中间体在本合成路线中的序号：(II)

Adenosylcobalamin-b-monocarboxylic acid (I) was coupled to 1,4-butanediamine (II) in the presence of EDC and HOBt to afford the N-(4-aminobutyl)amide (III). Subsequent acylation of amino amide (III) by diethylenetriaminopentaacetic dianhydride (IV) gave rise to the title compound.

参考文献中间体

合成目标

【1】 Hogenkamp, H.P.C.; Collins, D.A.; Transcobalamin II receptor imaging via radiolabeled diethylene-triaminepentaacetate cobalamin analogs. J Nucl Med 1997, 38, 5, 717.
【2】 Collins, D.A.; Hogenkamp, H.P.C. (Mayo Foundation for Medical Education and Research; University of Minnesota); Radionuclide labeling of vitamin B12 and coenzymes thereof. WO 9718231 .

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)	55155			C₇₂H₉₉CoN₁₇O₁₈P	详情	详情
(II)	42070	1,4-butanediamine; 4-aminobutylamine	110-60-1	C₄H₁₂N₂	详情	详情
(III)	55156			C₇₆H₁₀₉CoN₁₉O₁₇P	详情	详情
(IV)	49150	Diethylenetriaminepentaacetic acid; N,N-Bis[2-(2,6-dioxomorpholino)ethyl]glycine	23911-26-4	C₁₄H₁₉N₃O₈	详情	详情

合成路线6

该中间体在本合成路线中的序号：(XVIII)

The tripyrrolyl acid (XII) is coupled with N,N-dimethyl-1,3-propanediamine (XIII) to afford amide (XIV). After acidic Boc group cleavage in (XIV), the resultant amino compound (XV) is acylated by 4,5-dichloroisothiazole-3-carboxylic acid (XVI) to furnish the tetra-heterocyclic amide (XVII). Finally, selective displacement of the 5-chloro group of (XVII) with 1,4-butanediamine (XVIII) gives rise to the title compound.

参考文献中间体

合成目标

【1】 Ge, Y.; Taylor, M.J.; Baird, E.E.; Moser, H.E.; Burli, R.W. (GeneSoft, Inc.); Charged cpds. comprising a nucleic acid binding moiety and uses therefor. JP 2003529609; WO 0174898 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XII)	53515	4-[({4-[({4-[(tert-butoxycarbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrol-2-yl}carbonyl)amino]-1-methyl-1H-pyrrole-2-carboxylic acid	n/a	C₂₃H₂₈N₆O₆	详情	详情
(XIII)	25248	N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine	109-55-7	C₅H₁₄N₂	详情	详情
(XIV)	58476	tert-butyl 5-({[5-({[5-({[3-(dimethylamino)propyl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-ylcarbamate		C₂₈H₄₀N₈O₅	详情	详情
(XV)	58477	4-{[(4-{[(4-amino-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-1-methyl-1H-pyrrol-2-yl)carbonyl]amino}-N-[3-(dimethylamino)propyl]-1-methyl-1H-pyrrole-2-carboxamide		C₂₃H₃₂N₈O₃	详情	详情
(XVI)	53577	((3aR,4R,6R,6aS)-2,2-dimethyl-6-{6-[(3R)tetrahydro-3-furanylamino]-9H-purin-9-yl}tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl methylcarbamate	n/a	C₁₉H₂₆N₆O₆	详情	详情
(XVII)	58478	4,5-dichloro-N-[5-({[5-({[5-({[3-(dimethylamino)propyl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]amino}carbonyl)-1-methyl-1H-pyrrol-3-yl]-3-isothiazolecarboxamide		C₂₇H₃₁Cl₂N₉O₄S	详情	详情
(XVIII)	42070	1,4-butanediamine; 4-aminobutylamine	110-60-1	C₄H₁₂N₂	详情	详情

Extended Information