1,4-bis(4-bromophenyl)-1,4-butanedione -Drug Synthesis Database

【结构式】

【分子编号】35811

【品名】1,4-bis(4-bromophenyl)-1,4-butanedione

【CA登记号】

【分子式】C₁₆H₁₂Br₂O₂

【分子量】396.07808

【元素组成】C 48.52% H 3.05% Br 40.35% O 8.08%

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：(IV)

The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III), which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV). The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V), which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI). The reaction of (VI) with HCl in ethanol gives the bis imidate (VII), which is finally treated with O-methylhydroxylamine to yield the target bis O-methylamidooxime.

参考文献中间体

合成目标

【3】 Tidwell, R.R.; Hall, J.E.; Kumar, A.; Dykstra, C.C.; Boykin, D.W.; Wilson, W.D.; Blagburn, B.L. (Auburn University; Georgia State University; University of North Carolina); Furan derivs. for inhibiting Pneumocystis carinii pneumonia, Giardia lamblia and Cryptosporidium parvum. WO 9615126 .
【1】 Boykin, D.W.; et al.; Anti-pneumocystis activity of bis-amidoximes and bis-O-alkylamidoximes prodrugs. Bioorg Med Chem Lett 1996, 6, 24, 3017.
【2】 Boykin, D.W.; et al.; 2,5-Bis[4-(N-alkylamidino)phenyl]furans as anti-Pneumocystis carinii agents. J Med Chem 1998, 41, 1, 124.

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)	57909	Fumaryl chloride	627-63-4	C₄H₂Cl₂O₂	详情	详情
(II)	13365	Monobromobenzene; 1-Bromobenzene；Phenylbromide;bromobenzene	108-86-1	C₆H₅Br	详情	详情
(III)	57910	(E)-1,4-bis(4-bromophenyl)-2-butene-1,4-dione		C₁₆H₁₀Br₂O₂	详情	详情
(IV)	35811	1,4-bis(4-bromophenyl)-1,4-butanedione		C₁₆H₁₂Br₂O₂	详情	详情
(V)	35812	2,5-bis(4-bromophenyl)furan		C₁₆H₁₀Br₂O	详情	详情
(VI)	35814	4-[5-(4-cyanophenyl)-2-furyl]benzonitrile		C₁₈H₁₀N₂O	详情	详情
(VII)	35815	ethyl 4-(5-[4-[ethoxy(imino)methyl]phenyl]-2-furyl)benzenecarboximidoate		C₂₂H₂₂N₂O₃	详情	详情
(VIII)	15455	(aminooxy)methane; O-methylhydroxylamine	67-62-9	CH₅NO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The Friedel Crafts condensation of fumaryl chloride (I) with bromobenzene (II) gives 1,2-bis(4-bromobenzoyl)ethylene (III), which is reduced with Zn and Ac-OH to yield 1,4-bis(4-bromophenyl)butane-1,4-dione (IV). The cyclization of (IV) in refluxing Ac2O affords 2,5-bis(4-bromophenyl)furan (V) which is treated with CNCu in refluxing quinoline to provide 2,5-bis(4-cyanophenyl)furan (VI). The reaction of (VI) with HCl in ethanol gives the bis imidate (VII), which is finally treated with ammonia in ethanol to yield the target bis benzamidine.

参考文献中间体

合成目标

【1】 Dann, O.; et al.; Trypanocidal diamidines with three isolated ring systems. Liebigs Ann Chem 1975, 1, 160.
【2】 Das, B.P.; Boykin, D.W.; Synthesis and antiprotozoal activity of 2,5-bis (4-guanylphenyl) furans. J Med Chem 1977, 20, 4, 531-536.
【3】 Boykin, D.W.; et al.; 2,5-Bis[4-(N-alkylamidino)phenyl]furans as anti-Pneumocystis carinii agents. J Med Chem 1998, 41, 1, 124.
【4】 Boykin, D.W.; et al.; Anti-pneumocystis activity of bis-amidoximes and bis-O-alkylamidoximes prodrugs. Bioorg Med Chem Lett 1996, 6, 24, 3017.
【5】 Niigata, K.; Murakami, M.; Kagami, S.; Fujikura, S.; Kojima, A.; Tachikawa, S.; Nozaki, J.; Takahashi, K. (Yamanouchi Pharmaceutical Co., Ltd.); Novel indene derivs. or their salts. JP 1977111580 .

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)	57909	Fumaryl chloride	627-63-4	C₄H₂Cl₂O₂	详情	详情
(II)	13365	Monobromobenzene; 1-Bromobenzene；Phenylbromide;bromobenzene	108-86-1	C₆H₅Br	详情	详情
(III)	57910	(E)-1,4-bis(4-bromophenyl)-2-butene-1,4-dione		C₁₆H₁₀Br₂O₂	详情	详情
(IV)	35811	1,4-bis(4-bromophenyl)-1,4-butanedione		C₁₆H₁₂Br₂O₂	详情	详情
(V)	35812	2,5-bis(4-bromophenyl)furan		C₁₆H₁₀Br₂O	详情	详情
(VI)	56856	Copper (I) cyanide; Cuprous cyanide	544-92-3	CCuN	详情	详情
(VII)	35814	4-[5-(4-cyanophenyl)-2-furyl]benzonitrile		C₁₈H₁₀N₂O	详情	详情
(VIII)	35815	ethyl 4-(5-[4-[ethoxy(imino)methyl]phenyl]-2-furyl)benzenecarboximidoate		C₂₂H₂₂N₂O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

2,5-Bis(p-bromophenyl)furan (II) was prepared by cyclodehydration of diketone (I) in refluxing acetic anhydride. Displacement of both bromine atoms by copper(I) cyanide in boiling quinoline generated the dicyano derivative (V). Alternatively, furan (V) was prepared by addition of p-cyanobenzaldehyde (III) to divinyl sulfone (IV) in the presence of a thiazolium catalyst. After conversion of the cyano groups of (V) into bis-imidate (VI), reaccion with ethanolic ammonia furnished amidine (VII). The stable symmetrical carbonate (X) was obtained by reaction of p-fluorophenyl chloroformate (VIII) with p-fluorophenol (IX) in the presence of pyridine. Finally, reaction of the bis(amidine) compound (VII) with carbonate (X) yielded the title compound.

参考文献中间体

合成目标

【1】 Kawada, A.; Aragane, Y.; Maeda, A.; Tezuka, T.; Heterocycl Commun 1996, 2, 2, 135-140.
【2】 Das, B.P.; Boykin, D.W.; Synthesis and antiprotozoal activity of 2,5-bis (4-guanylphenyl) furans. J Med Chem 1977, 20, 4, 531-536.
【3】 Rahmathullah, S.M.; et al.; Prodrugs for amidines: Synthesis and anti-Pneumocystis carinii activity of carbamates of 2,5-bis(4-amidinophenyl)furan. J Med Chem 1999, 42, 19, 3994.

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)	35811	1,4-bis(4-bromophenyl)-1,4-butanedione		C₁₆H₁₂Br₂O₂	详情	详情
(II)	35812	2,5-bis(4-bromophenyl)furan		C₁₆H₁₀Br₂O	详情	详情
(III)	17552	4-formylbenzonitrile; 4-Cyanobenzaldehyde	105-07-7	C₈H₅NO	详情	详情
(IV)	35813	divinyl sulfone; dioxo(divinyl)-lambda(6)-sulfane	77-77-0	C₄H₆O₂S	详情	详情
(V)	35814	4-[5-(4-cyanophenyl)-2-furyl]benzonitrile		C₁₈H₁₀N₂O	详情	详情
(VI)	35815	ethyl 4-(5-[4-[ethoxy(imino)methyl]phenyl]-2-furyl)benzenecarboximidoate		C₂₂H₂₂N₂O₃	详情	详情
(VII)	35816	4-(5-[4-[amino(imino)methyl]phenyl]-2-furyl)benzenecarboximidamide		C₁₈H₁₆N₄O	详情	详情
(VIII)	35817	1-[(chlorocarbonyl)oxy]-4-fluorobenzene	38377-38-7	C₇H₄ClFO₂	详情	详情
(IX)	19639	4-fluorophenol	371-41-5	C₆H₅FO	详情	详情
(X)	35818	bis(4-fluorophenyl) carbonate		C₁₃H₈F₂O₃	详情	详情

Extended Information