【结 构 式】 |
【分子编号】57909 【品名】Fumaryl chloride 【CA登记号】627-63-4 |
【 分 子 式 】C4H2Cl2O2 【 分 子 量 】152.96408 【元素组成】C 31.41% H 1.32% Cl 46.35% O 20.92% |
合成路线1
该中间体在本合成路线中的序号:(I)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.
【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:(I)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.
【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 |