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【结 构 式】 
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【分子编号】18003 【品名】4,5-dichloro-1,2-benzenediamine; 4,5-Dichloro-o-phenylenediamine; 2-amino-4,5-dichlorophenylamine 【CA登记号】5348-42-5 |
【 分 子 式 】C6H6Cl2N2 【 分 子 量 】177.03252 【元素组成】C 40.71% H 3.42% Cl 40.05% N 15.82% |
合成路线1
该中间体在本合成路线中的序号：(IV)Phenylenediamine (IV) was protected as the benzoselenadiazole (V) on treatment with selenium dioxide in 1 N HCl. The subsequent nitration with nitric and sulfuric acid provided (VI), which on stirring with a mixture of concentrated HCl and HI gave the nitrodiamine (VII). Cyclization of (VII) with labeled diethyl oxalate (III) in sulfuric acid at 175 C yielded labeled quinoxalinedione.
| 【1】 Thorell, J.O.; et al.; Synthesis of a C-11-labelled nitrated 1,4-dihydroquinoxaline-2,3-dione, the NMDA glycine receptor antagonist ACEA 1021 (Licostinel). J Label Compd Radiopharm 1998, 41, 4, 345-353. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 17571 | Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate | 95-92-1 | C6H10O4 | 详情 | 详情 |
| (III) | 45301 | ethyl 2-ethoxy-2-oxoacetate | C6H10O4 | 详情 | 详情 | |
| (IV) | 18003 | 4,5-dichloro-1,2-benzenediamine; 4,5-Dichloro-o-phenylenediamine; 2-amino-4,5-dichlorophenylamine | 5348-42-5 | C6H6Cl2N2 | 详情 | 详情 |
| (V) | 18004 | 5,6-dichloro-2,1,3-benzoselenadiazole | C6H2Cl2N2Se | 详情 | 详情 | |
| (VI) | 18005 | 5,6-dichloro-4-nitro-2,1,3-benzoselenadiazole | C6HCl2N3O2Se | 详情 | 详情 | |
| (VII) | 18006 | 2-amino-4,5-dichloro-3-nitrophenylamine; 4,5-dichloro-3-nitro-1,2-benzenediamine | C6H5Cl2N3O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Alternatively, condensation of phenylenediamine (IV) with oxalate (III) in hot sulfuric acid afforded labeled quinoxalinedione (VIII), to which was added acetic acid or diethyl oxalate in order to protect amino groups, and was then nitrated with fuming nitric acid and sulfuric acid.
| 【1】 Thorell, J.O.; et al.; Synthesis of a C-11-labelled nitrated 1,4-dihydroquinoxaline-2,3-dione, the NMDA glycine receptor antagonist ACEA 1021 (Licostinel). J Label Compd Radiopharm 1998, 41, 4, 345-353. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 17571 | Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate | 95-92-1 | C6H10O4 | 详情 | 详情 |
| (III) | 45301 | ethyl 2-ethoxy-2-oxoacetate | C6H10O4 | 详情 | 详情 | |
| (IV) | 18003 | 4,5-dichloro-1,2-benzenediamine; 4,5-Dichloro-o-phenylenediamine; 2-amino-4,5-dichlorophenylamine | 5348-42-5 | C6H6Cl2N2 | 详情 | 详情 |
| (VIII) | 18007 | 6,7-dichloro-1,4-dihydro-2,3-quinoxalinedione | 25983-13-5 | C8H4Cl2N2O2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)Condensation of 4,5-dichloro-1,2-phenylenediamine (I) with 1-phenyl-1,2-propanedione (II) in boiling AcOH provided quinoxaline (III). Subsequent reaction of (III) with ethyl bromopyruvate (IV) led to the pyrroloquinoxaline (V). After reduction of the ester group of (V) to alcohol (VI) with LiAlH4, further oxidation with MnO2 produced aldehyde (VII). This was condensed with boiling 3-(dimethylamino)propylamine (VIII), and the resulting imine (IX) was finally reduced to the target amine with NaBH4 in MeOH. The title compound was finally converted to the dioxalate salt upon treatment with oxalic acid in isopropanol.
| 【1】 Guillon, J.; Rault, S.; Kervran, A.; Renard, P.; Manechez, D.; Pfeiffer, B.; Dallemagne, P.; Synthesis of new pyrrolo[1,2-a]quinoxalines: Potential non-peptide glucagon receptor antagonists. Eur J Med Chem 1998, 33, 4, 293. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 15713 | Oxalic acid | 144-62-7 | C2H2O4 | 详情 | 详情 | |
| (I) | 18003 | 4,5-dichloro-1,2-benzenediamine; 4,5-Dichloro-o-phenylenediamine; 2-amino-4,5-dichlorophenylamine | 5348-42-5 | C6H6Cl2N2 | 详情 | 详情 |
| (II) | 31481 | 1-phenyl-1,2-propanedione | 579-07-7 | C9H8O2 | 详情 | 详情 |
| (III) | 31482 | 6,7-dichloro-2-methyl-3-phenylquinoxaline | C15H10Cl2N2 | 详情 | 详情 | |
| (IV) | 25183 | ethyl 3-bromo-2-oxopropanoate;ethyl 3-bromopyruvate;Bromopyruvic acid ethyl ester;ethyl 3-bromopyruvate;ethyl bromopyruvate | 70-23-5 | C5H7BrO3 | 详情 | 详情 |
| (V) | 31483 | ethyl 7,8-dichloro-4-phenylpyrrolo[1,2-a]quinoxaline-2-carboxylate | C20H14Cl2N2O2 | 详情 | 详情 | |
| (VI) | 31484 | (7,8-dichloro-4-phenylpyrrolo[1,2-a]quinoxalin-2-yl)methanol | C18H12Cl2N2O | 详情 | 详情 | |
| (VII) | 31486 | 7,8-dichloro-4-phenylpyrrolo[1,2-a]quinoxaline-2-carbaldehyde | C18H10Cl2N2O | 详情 | 详情 | |
| (VIII) | 25248 | N-(3-aminopropyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,3-propanediamine | 109-55-7 | C5H14N2 | 详情 | 详情 |
| (IX) | 31485 | N(1)-[(E)-(7,8-dichloro-4-phenylpyrrolo[1,2-a]quinoxalin-2-yl)methylidene]-N(3),N(3)-dimethyl-1,3-propanediamine; N-[(E)-(7,8-dichloro-4-phenylpyrrolo[1,2-a]quinoxalin-2-yl)methylidene]-N-[3-(dimethylamino)propyl]amine | C23H22Cl2N4 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(I)The condensation of 4,5-dichloro-1,2-phenylenediamine (I) with diethyl oxalate (II) produced quinoxalinedione (III), which was brominated with PBr5 at 155 C to afford the dibromo derivative (IV). Displacement of one bromine group of (IV) with 4-(diethylamino)butylamine (V) furnished (VI). The remaining bromine of (VI) was then displaced with 5-(tributylstannyl)-2,2'-bithienyl (VII) to produce the title compound, isolated as the corresponding hydrochloride salt.
| 【1】 Li, J.J.; Yue, W.-S.; Trivedi, B.K.; et al.; Structure-activity relationship of 2-amino-3-heteroaryl-quinoxalines as potent, non-peptide interleukine-8-receptor antagonists. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 144. |
| 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) | 18003 | 4,5-dichloro-1,2-benzenediamine; 4,5-Dichloro-o-phenylenediamine; 2-amino-4,5-dichlorophenylamine | 5348-42-5 | C6H6Cl2N2 | 详情 | 详情 |
| (II) | 17571 | Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate | 95-92-1 | C6H10O4 | 详情 | 详情 |
| (III) | 18007 | 6,7-dichloro-1,4-dihydro-2,3-quinoxalinedione | 25983-13-5 | C8H4Cl2N2O2 | 详情 | 详情 |
| (IV) | 44243 | 2,3-dibromo-6,7-dichloroquinoxaline | C8H2Br2Cl2N2 | 详情 | 详情 | |
| (V) | 44244 | N-(4-aminobutyl)-N,N-diethylamine; N(1),N(1)-diethyl-1,4-butanediamine | C8H20N2 | 详情 | 详情 | |
| (VI) | 44245 | N-(3-bromo-6,7-dichloro-2-quinoxalinyl)-N-[4-(diethylamino)butyl]amine; N(1)-(3-bromo-6,7-dichloro-2-quinoxalinyl)-N(4),N(4)-diethyl-1,4-butanediamine | C16H21BrCl2N4 | 详情 | 详情 | |
| (VII) | 44246 | C20H32S2Sn | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(I)The condensation of 4,5-dichloro-1,2-phenylenediamine (I) with diethyl oxalate (II) produced quinoxalinedione (III), which was brominated with PBr5 at 155 C to afford the dibromo derivative (IV). Displacement of one bromine group of (IV) with 4-(diethylamino)butylamine (V) furnished (VI). The remaining bromine of (VI) was then displaced with 2-(tributylstannyl)benzofuran (VII) to produce the title compound.
| 【1】 Li, J.J.; Yue, W.-S.; Trivedi, B.K.; et al.; Structure-activity relationship of 2-amino-3-heteroaryl-quinoxalines as potent, non-peptide interleukine-8-receptor antagonists. 220th ACS Natl Meet (Aug 20 2000, Washington DC) 2000, Abst MEDI 144. |
| 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) | 18003 | 4,5-dichloro-1,2-benzenediamine; 4,5-Dichloro-o-phenylenediamine; 2-amino-4,5-dichlorophenylamine | 5348-42-5 | C6H6Cl2N2 | 详情 | 详情 |
| (II) | 17571 | Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate | 95-92-1 | C6H10O4 | 详情 | 详情 |
| (III) | 18007 | 6,7-dichloro-1,4-dihydro-2,3-quinoxalinedione | 25983-13-5 | C8H4Cl2N2O2 | 详情 | 详情 |
| (IV) | 44243 | 2,3-dibromo-6,7-dichloroquinoxaline | C8H2Br2Cl2N2 | 详情 | 详情 | |
| (V) | 44244 | N-(4-aminobutyl)-N,N-diethylamine; N(1),N(1)-diethyl-1,4-butanediamine | C8H20N2 | 详情 | 详情 | |
| (VI) | 44245 | N-(3-bromo-6,7-dichloro-2-quinoxalinyl)-N-[4-(diethylamino)butyl]amine; N(1)-(3-bromo-6,7-dichloro-2-quinoxalinyl)-N(4),N(4)-diethyl-1,4-butanediamine | C16H21BrCl2N4 | 详情 | 详情 | |
| (VII) | 44247 | 1-benzofuran-2-yl(tributyl)stannane | C20H32OSn | 详情 | 详情 |