【结 构 式】 |
【分子编号】68667 【品名】2-amino-5-nitrobenzene-1-sulfonyl chloride 【CA登记号】 |
【 分 子 式 】C6H5ClN2O4S 【 分 子 量 】236.63548 【元素组成】C 30.45% H 2.13% Cl 14.98% N 11.84% O 27.04% S 13.55% |
合成路线1
该中间体在本合成路线中的序号:(XIX)Chlorination of 2-chloro-5-nitrobenzenesulfonic acid (XIV) with SOCl2 in refluxing DMF gives the sulfonyl chloride (XV), which is converted to the corresponding sulfonamide (XVI) by treatment with NH4OH in toluene/THF. Amination of the chloro sulfonamide (XVI) with (NH4)2CO3 and NH4OH in the presence of CuSO4 at 118 °C leads to 2-amino-5-nitrobenzenesulfonamide (XVII). Alternatively, chlorination of 2-amino-5-nitrobenzenesulfonic acid (XVIII) using POCl3 in sulfolane at 110-120 °C provides the corresponding sulfonyl chloride (XIX), which is treated with NH4OH to yield sulfonamide (XVII). Reduction of the nitro moiety of compound (XVII) with H2 over Pd/C in the presence of MsOH in EtOH/H2O at 55 °C affords 2,5-diaminobenzenesulfonamide mesylate (XX), which can also be obtained by chloride substitution in 2-chloro-5-nitrobenzenesulfonamide (XVI) with benzylamine by means of Et3N in acetonitrile at 92 °C, followed by hydrogenolysis of the resulting 2-(benzylamino)-5-nitrobenzenesulfonamide (XXI) over Pd/C in the presence of MsOH in THF/EtOH/H2O. Selective N-sulfonylation of diamine (XX) with methanesulfonyl chloride (XXII) and pyridine in CH2Cl2 or acetonitrile gives rise to 2-amino-5-(methylsulfonamido)benzenesulfonamide (XXIII), which is then condensed with either methyl malonyl chloride (XXIV) in THF or ethyl malonyl chloride (XXV) in DMF/Et2O or DMA , yielding amides (XXVI) or (XXVII). Finally, carbamoyl sulfonamides (XXVI) and (XXVII) are cyclized and simultaneously hydrolyzed by treatment with NaOH (XII) .
【1】 Tran, C.V., Ruebsam, F., Murphy, D.E. et al. (Anadys Pharmaceuticals, Inc.). 5,6-Dihydro-1H-pyridin-2-one compounds. CA 2682584, EP 2129224, JP 2010523586, US 2010034773, US 7939524, US 8101800, US 2012130068, US 8236948, WO 2008124450. |
【2】 Dragovich, P.S., Thompson, P.A., Ruebsam, F. (Anadys Pharmaceuticals, Inc.). A method of inhibiting hepatitis C virus by combination of a 5,6-dihydro-1H-pyridin-2-one and one or more additional antiviral compounds. EP 2346329, US 2011229438, WO 2010042834. |
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) | 68662 | 2-(7-(methylsulfonamido)-1,1-dioxido-4H-benzo[e][1,2,4]thiadiazin-3-yl)acetic acid | C10H11N3O6S2 | 详情 | 详情 | |
(XIV) | 68665 | 2-chloro-5-nitrobenzenesulfonic acid;2-Chloro-5-nitrobenzene sulfonic acid;p-Nitrochlorobenzene-o-sulfonic acid;2-chloro-5-nitro-Benzenesulfonic acid;2-chloro-5-nitrobenzenesulphonic acid | 96-73-1 | C6H4ClNO5S | 详情 | 详情 |
(XV) | 43034 | 2-chloro-5-nitrobenzenesulfonyl chloride;2-Chloro-5-nitro-benzenesulfonyl chloride;2-Chloro-5-nitrophenylsulfonyl chloride;6-Chloro-3-nitrobenzenesulfonyl chloride | 4533-95-3 | C6H3Cl2NO4S | 详情 | 详情 |
(XVI) | 43035 | 2-chloro-5-nitrobenzenesulfonamide | 96-72-0 | C6H5ClN2O4S | 详情 | 详情 |
(XVII) | 68666 | 2-amino-5-nitrobenzenesulfonamide | C6H7N3O4S | 详情 | 详情 | |
(XVIII) | 68668 | 2-amino-5-nitrobenzenesulfonic acid | 96-75-3 | C6H6N2O5S | 详情 | 详情 |
(XIX) | 68667 | 2-amino-5-nitrobenzene-1-sulfonyl chloride | C6H5ClN2O4S | 详情 | 详情 | |
(XX) | 68669 | 2,5-diaminobenzenesulfonamide mesylate;2,5-diaminobenzenesulfonamide methanesulfonate | C6H9N3O2S.CH4O3S | 详情 | 详情 | |
(XXI) | 68670 | 2-(benzylamino)-5-nitrobenzenesulfonamide | C13H13N3O4S | 详情 | 详情 | |
(XXII) | 13467 | Methanesulfonyl chloride;Mesyl chloride;Methylsulfonyl chloride;Methanesulfonic acid chloride;Methanesulfonyl chloride;Methanesulphonyl chloride | 124-63-0 | CH3ClO2S | 详情 | 详情 |
(XXIII) | 68671 | 2-amino-5-(methylsulfonamido)benzenesulfonamide | C7H11N3O4S2 | 详情 | 详情 | |
(XXIV) | 50272 | Malonic acid monomethyl ester chloride; Methyl (chloroformyl)acetate; Methyl malonyl chloride ;Methyl 3-chloro-3-oxopropionate | 37517-81-0 | C4H5ClO3 | 详情 | 详情 |
(XXV) | 13188 | ethyl 3-chloro-3-oxopropanoate; 2-Ethoxycarbonylacetyl chloride; Ethyl malonyl chloride | 36239-09-5 | C5H7ClO3 | 详情 | 详情 |
(XXVI) | 68672 | methyl 3-((4-(methylsulfonamido)-2-sulfamoylphenyl)amino)-3-oxopropanoate | C11H15N3O7S2 | 详情 | 详情 | |
(XXVII) | 68673 | ethyl 3-((4-(methylsulfonamido)-2-sulfamoylphenyl)amino)-3-oxopropanoate | C12H17N3O7S2 | 详情 | 详情 |