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【结 构 式】 
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【分子编号】25241 【品名】N-(5-chloro-2-nitrophenyl)acetamide 【CA登记号】39163-92-3 |
【 分 子 式 】C8H7ClN2O3 【 分 子 量 】214.60796 【元素组成】C 44.77% H 3.29% Cl 16.52% N 13.05% O 22.37% |
合成路线1
该中间体在本合成路线中的序号：(I)The condensation of 3-chloro-6-nitroacetanilide (I) with propylmercaptane (A) by means of aqueous refluxing NaOH gives 2-nitro-5-propylthioaniline (II), which was reduced with H2 over Pd/C in ethanol HCl to yield 4-propylthio-o-phenylenediamine (III). The cyclization of (III) with cyanogen bromide affords 2-amino-5-propylthiobenzimidazole (IV), which is finally condensed with methyl chloroformate. It can be condensed directly with a mixture of cyanamide and methyl chloroformate or with carbomethoxycyanamide (B). All these condensations are performed in basic medium.
| 【1】 Gyurik, R.J.; Theodorides, V.J.; Methyl 5-propylthio-2-benzimidazolecarbamate. DE 2527065; FR 2275203; GB 1464326; JP 51012936; US 3915986 . |
| 【2】 Bogan, J.; Castaner, J.; Albendazole. Drugs Fut 1977, 2, 2, 81. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 23703 | propylhydrosulfide; 1-propanethiol | 107-03-9 | C3H8S | 详情 | 详情 |
| (B) | 33600 | methyl cyanocarbamate | C3H4N2O2 | 详情 | 详情 | |
| (I) | 25241 | N-(5-chloro-2-nitrophenyl)acetamide | 39163-92-3 | C8H7ClN2O3 | 详情 | 详情 |
| (II) | 33597 | 2-nitro-5-(propylsulfanyl)phenylamine; 2-nitro-5-(propylsulfanyl)aniline | C9H12N2O2S | 详情 | 详情 | |
| (III) | 33598 | 4-(propylsulfanyl)-1,2-benzenediamine; 2-amino-4-(propylsulfanyl)phenylamine; 2-Amino-5-propylthioaniline | 66608-52-4 | C9H14N2S | 详情 | 详情 |
| (IV) | 33599 | 5-(propylsulfanyl)-1H-benzimidazol-2-ylamine; 5-(propylsulfanyl)-1H-benzimidazol-2-amine | C10H13N3S | 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 acetylation of 3-chloroaniline (I) with refluxing acetic anhydride gives the corresponding anilide (II), which is nitrated with HNO3/H2SO4 yielding 5-chloro-2-nitroacetanilide (III). The hydrolysis of (III) with hot conc. H2SO4 affords 5-chloro-2-nitroaniline (IV), which is treated with NaNO2/HCl to afford the corresponding diazonium salt (V). The reaction of (V) with sodium azide gives 2-nitro-5-chlorophenylazide (VI), which is cyclized to 5-chlorobenzofurazan-3-oxide (VII) in refluxing toluene. The condensation of (VII) with malononitrile (VIII) in DMF in the presence of a catalytic amount of triethylamine afforded a mixture of the isomeric quinoxaline-di-N-oxides (IX and X), which were separated by flash chromatography. The 7-chloro isomer (XI) was then submitted to diazotization with tert-butyl nitrite in acetonitrile in the presence of cupric chloride, which effected a Sandmeyer reaction to give the 2,6-dichloro derivative (XI). N-Alkylation of 3-(N,N-dimethylamino)propylamine (XII) with intermediate (XI) in dichloromethane in the presence of potassium carbonate, followed by treatment with concentrated hydrochloric acid in acetone afforded the title compound.
| 【1】 Monge, A.; et al.; Hypoxia-selective agents derived from quinoxaline 1, 4-di-N-oxides. J Med Chem 1995, 38, 10, 1786. |
| 【2】 Monge, A.; et al.; Hypoxia-selective agents derived from 2-quinoxalinecarbonitrile 1,4-di-N-oxides. 2. J Med Chem 1995, 38, 22, 4488. |
| 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) | 25239 | 3-chloroaniline; 3-chlorophenylamine | 108-42-9 | C6H6ClN | 详情 | 详情 |
| (II) | 25240 | N-(3-chlorophenyl)acetamide | 588-07-8 | C8H8ClNO | 详情 | 详情 |
| (III) | 25241 | N-(5-chloro-2-nitrophenyl)acetamide | 39163-92-3 | C8H7ClN2O3 | 详情 | 详情 |
| (IV) | 15709 | 5-chloro-2-nitrophenylamine; 5-chloro-2-nitroaniline | 1635-61-6 | C6H5ClN2O2 | 详情 | 详情 |
| (V) | 25242 | 5-chloro-2-nitrobenzenediazonium chloride | 2589-71-1 | C6H3Cl2N3O2 | 详情 | 详情 |
| (VI) | 25243 | 2-azido-4-chloro-1-nitrobenzene | C6H3ClN4O2 | 详情 | 详情 | |
| (VII) | 25244 | 7-chloro-4a,8a-dihydro-1-quinoliniumolate | C9H8ClNO | 详情 | 详情 | |
| (VIII) | 12061 | Malononitrile | 109-77-3 | C3H2N2 | 详情 | 详情 |
| (IX) | 25245 | 2-amino-6-chloro-3-cyano-1,4-quinoxalinediiumdiolate | C9H5ClN4O2 | 详情 | 详情 | |
| (X) | 25246 | 3-amino-6-chloro-2-cyano-1,4-quinoxalinediiumdiolate | C9H5ClN4O2 | 详情 | 详情 | |
| (XI) | 25247 | 2,6-dichloro-3-cyano-1,4-quinoxalinediiumdiolate | C9H3Cl2N3O2 | 详情 | 详情 | |
| (XII) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |