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【结 构 式】 
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【分子编号】10328 【品名】5-Bromo-6-quinoxalinamine; 5-Bromo-6-quinoxalinylamine 【CA登记号】 |
【 分 子 式 】C8H6BrN3 【 分 子 量 】224.05986 【元素组成】C 42.88% H 2.7% Br 35.66% N 18.75% |
合成路线1
该中间体在本合成路线中的序号：(I)Several degradation products and metabolites of brimonidine have been synthesized: 1) The reaction of 5-bromoquinoxalin-6-amine (I) with cyanamide (II) and HCl in refluxing dioxane gives N2-(5-bromoquinoxalin-6-yl)guanidine (AGN-191383). 2) The reaction of AGN-191383 with 1,1'-oxalyldiimidazole (III) and dimethylaminopyridine (DMAP) in pyridine yields 2-(5-bromoquinoxalin-6-ylimino)imidazolidine-4,5-dione (AGN-192597). 3) The reaction of AGN-191383 with sodium iodoacetate (IV) in DMSO and then acidification with HCl affords 2-[N2-(5-bromoquinoxalin-6-yl)guanidino]acetic acid (AGN-192614).
| 【1】 Tang-Liu, D.; Burke, J.; Garst, M.; Harcourt, D.; Acheampong, A.; Breau, A.; Munk, S.A.; Wong, H.; Lai, R.; Wheeler, L.; Synthesis and characterization of degradation products and metabolites of brimonidine - A potent alpha2 adrenergic agonist. 211th ACS Natl Meet (March 24-28, New Orleans) 1996, Abst MEDI 021. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| AGN-191383 | 62982 | N''-(5-bromo-6-quinoxalinyl)guanidine | C9H8BrN5 | 详情 | 详情 | |
| AGN-192614 | 62983 | 2-({amino[(5-bromo-6-quinoxalinyl)imino]methyl}amino)acetic acid | C11H10BrN5O2 | 详情 | 详情 | |
| AGN-192597 | 62984 | 2-[(5-bromo-6-quinoxalinyl)imino]-4,5-imidazolidinedione | C11H6BrN5O2 | 详情 | 详情 | |
| (I) | 10328 | 5-Bromo-6-quinoxalinamine; 5-Bromo-6-quinoxalinylamine | C8H6BrN3 | 详情 | 详情 | |
| (III) | 10329 | 1,2-Di(1H-imidazol-1-yl)-1,2-ethanedione; 1,1'-Oxalyldiimidazole | 18637-83-7 | C8H6N4O2 | 详情 | 详情 |
| (IV) | 62985 | sodium 2-iodoacetate | C2H2INaO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)4) The reaction of amine (I) with phenyl cyanate (V) and KH in THF gives N-(5-bromoquinoxalin-6-yl)cyanamide (VI), which is cyclized with ethyl glycinate (VII) in refluxing ethanol to yield 2-(5-bromoquinoxalin-6-imino)imidazolidin-4-one (AGN-192119). 5) The reaction of cyanamide (VI) with 2-aminoacetaldehyde diethyl acetal (VIII) affords N1-(5-bromoquinoxalin-6-yl)-N3-(2,2-diethoxyethyl)guanidine (IX), which is cyclized by means of HCl to the hydroxyimidazoline (X). Finally, this compound is treated with NaOH to afford 5-bromo-6-(2-imidazolylamino)quinoxaline (AGN-192076).
| 【1】 Tang-Liu, D.; Burke, J.; Garst, M.; Harcourt, D.; Acheampong, A.; Breau, A.; Munk, S.A.; Wong, H.; Lai, R.; Wheeler, L.; Synthesis and characterization of degradation products and metabolites of brimonidine - A potent alpha2 adrenergic agonist. 211th ACS Natl Meet (March 24-28, New Orleans) 1996, Abst MEDI 021. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| AGN-192119 | 62987 | 2-[(5-bromo-6-quinoxalinyl)imino]-4-imidazolidinone | C11H8BrN5O | 详情 | 详情 | |
| AGN-192076 | 62988 | 5-bromo-N-(1H-imidazol-2-yl)-6-quinoxalinamine; N-(5-bromo-6-quinoxalinyl)-N-(1H-imidazol-2-yl)amine | C11H8BrN5 | 详情 | 详情 | |
| (I) | 10328 | 5-Bromo-6-quinoxalinamine; 5-Bromo-6-quinoxalinylamine | C8H6BrN3 | 详情 | 详情 | |
| (V) | 62986 | phenyl cyanate | C7H5NO | 详情 | 详情 | |
| (VI) | 10330 | N-(5-Bromo-6-quinoxalinyl)cyanamide | C9H5BrN4 | 详情 | 详情 | |
| (VII) | 10309 | ethyl 2-aminoacetate; Glycine ethyl ester | 459-73-4 | C4H9NO2 | 详情 | 详情 |
| (VIII) | 10331 | 2,2-Diethoxy-1-ethanamine; 2,2-Diethoxyethylamine; Aminoacetaldehyde diethyl acetal | 645-36-3 | C6H15NO2 | 详情 | 详情 |
| (IX) | 10332 | N-(5-Bromo-6-quinoxalinyl)-N'-(2,2-diethoxyethyl)guanidine | C15H20BrN5O2 | 详情 | 详情 | |
| (X) | 10333 | 2-[(5-Bromo-6-quinoxalinyl)amino]-4,5-dihydro-1H-imidazol-5-ol | C11H10BrN5O | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)6) The reaction of amine (I) with phenyl chloroformate (XI) in pyridine gives N-(5-bromoquinoxalin-6-yl)carbamic acid phenyl ester (XII), which is then treated with ethylenediamine (XIII) to afford N-(2-aminoethyl)-N'-(5-bromoquinoxalin-6-yl)urea (AGN-192170)).
| 【1】 Tang-Liu, D.; Burke, J.; Garst, M.; Harcourt, D.; Acheampong, A.; Breau, A.; Munk, S.A.; Wong, H.; Lai, R.; Wheeler, L.; Synthesis and characterization of degradation products and metabolites of brimonidine - A potent alpha2 adrenergic agonist. 211th ACS Natl Meet (March 24-28, New Orleans) 1996, Abst MEDI 021. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| AGN-62989 | 62989 | N-(2-aminoethyl)-N'-(5-bromo-6-quinoxalinyl)urea | C11H12BrN5O | 详情 | 详情 | |
| (I) | 10328 | 5-Bromo-6-quinoxalinamine; 5-Bromo-6-quinoxalinylamine | C8H6BrN3 | 详情 | 详情 | |
| (XI) | 13580 | 1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate | 1885-14-9 | C7H5ClO2 | 详情 | 详情 |
| (XII) | 10335 | phenyl N-(5-bromo-6-quinoxalinyl)carbamate | C15H10BrN3O2 | 详情 | 详情 | |
| (XIII) | 14754 | ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine | 107-15-3 | C2H8N2 | 详情 | 详情 |