【结 构 式】 |
【分子编号】43035 【品名】2-chloro-5-nitrobenzenesulfonamide 【CA登记号】96-72-0 |
【 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:(III)The reaction of 2-chloro-5-nitroaniline (I) with NaNO2 in HCl and HOAc, followed by addition of CuCl2 and SO2 yields sulfonyl chloride (II). Reaction of (II) with NH4OH affords sulfonamide (III), which is then treated 3-methylaniline (IV) in 3-chlorotoluene to furnish intermediate (V). Final conversion of (V) into the target product is achieved by treatment in H2O/acetone with NaOH and carbamimidothioate (VIII), which can be obtained by reaction of dimethyl N-cyanodithioiminocarbonate (VI) with amine (VII) in EtOH.
【1】 Delarge, J.; Masereel, B.; Dogne, J.-M. (University of Liege); Benzenic sulphonamide derivs. and their uses. WO 0042004 . |
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) | 43033 | 2-chloro-5-nitroaniline; 2-chloro-5-nitrophenylamine | 6283-25-6 | C6H5ClN2O2 | 详情 | 详情 |
(II) | 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 |
(III) | 43035 | 2-chloro-5-nitrobenzenesulfonamide | 96-72-0 | C6H5ClN2O4S | 详情 | 详情 |
(IV) | 30687 | 3-methylphenylamine; m-toluidine | 108-44-1 | C7H9N | 详情 | 详情 |
(V) | 43036 | 5-nitro-2-(3-toluidino)benzenesulfonamide | C13H13N3O4S | 详情 | 详情 | |
(VI) | 43037 | [[bis(methylsulfanyl)methylene]amino]methane | C4H9NS2 | 详情 | 详情 | |
(VII) | 18672 | azepane | 111-49-9 | C6H13N | 详情 | 详情 |
(VIII) | 43038 | methyl N-cyano-1-azepanecarbimidothioate | C9H15N3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(III)Diazotization of 2-chloro-5-nitroaniline (I), followed by quenching with a solution of SO2 in HOAc in the presence of CuCl2, furnished the sulfonyl chloride (II). Treatment of (II) with aqueous ammonia gave rise to the corresponding sulfonamide (III). The chloro group of (III) was then displaced with cyclohexylamine (IV) in refluxing 3-chlorotoluene to afford the cyclohexylamino benzenesulfonamide (V). Finally, condensation of sulfonamide (V) with pentyl isocyanate (VI) produced the target sulfonylurea.
【1】 Delarge, J.; Masereel, B.; Dogne, J.-M. (University of Liege); Benzenic sulphonamide derivs. and their uses. WO 0042004 . |
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) | 43033 | 2-chloro-5-nitroaniline; 2-chloro-5-nitrophenylamine | 6283-25-6 | C6H5ClN2O2 | 详情 | 详情 |
(II) | 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 |
(III) | 43035 | 2-chloro-5-nitrobenzenesulfonamide | 96-72-0 | C6H5ClN2O4S | 详情 | 详情 |
(IV) | 17966 | cyclohexanamine; cyclohexyl amine; cyclohexylamine | 108-91-8 | C6H13N | 详情 | 详情 |
(V) | 47439 | 2-(cyclohexylamino)-5-nitrobenzenesulfonamide | C12H17N3O4S | 详情 | 详情 | |
(VI) | 47440 | 1-isocyanatopentane; pentyl isocyanate | 3954-13-0 | C6H11NO | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号:(XVI)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 |