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【结 构 式】 
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【分子编号】19144 【品名】N-(3-bromophenyl)-N-(7-fluoro-6-nitro-4-quinazolinyl)amine; N-(3-bromophenyl)-7-fluoro-6-nitro-4-quinazolinamine 【CA登记号】 |
【 分 子 式 】C14H8BrFN4O2 【 分 子 量 】363.1456832 【元素组成】C 46.3% H 2.22% Br 22% F 5.23% N 15.43% O 8.81% |
合成路线1
该中间体在本合成路线中的序号：(V)Nitration of quinazolinone (I) with fuming HNO3 in H2SO4 at 100 C gave a mixture of 6-nitro and 8-nitroquinazolines, from which the desired 6-isomer was isolated by recrystallization from AcOH. Subsequent treatment with refluxing SOCl2 and a catalytic amount of DMF gave chloride (III), which was condensed with 3-bromoaniline (IV) in isopropanol to afford anilinoquinazoline (V). Reaction with sodium alkoxide (VI) in refluxing THF provided ether (VII). Then, the nitro group was reduced with Fe dust and AcOH in aqueous ethanol to give amine (VIII). Finally, condensation with acrylic acid (X) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.HCl (EDC) in DMF yielded the target acrylamide.
| 【1】 Rewcastle, G.W.; et al.; Tyrosine kinase inhibitors. 9. Synthesis and evaluation of fused tricyclic quinazoline analogues as ATP site inhibitors of the tyrosine kinase activity of the epidermal growth factor receptor. J Med Chem 1996, 39, 4, 918. |
| 【2】 Dobrusin, E.M.; Bridges, A.J.; Zhou, H.; Smaill, J.B.; Doherty, A.M.; Denny, W.A.; McNamara, D.J.; Showalter, H.D. (Pfizer Inc.); Irreversible inhibitors of tyrosine kinases. JP 2000508657; WO 9738983 . |
| 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) | 19140 | 7-fluoro-4(3H)-quinazolinone | C8H5FN2O | 详情 | 详情 | |
| (II) | 19141 | 7-fluoro-6-nitro-4(3H)-quinazolinone | C8H4FN3O3 | 详情 | 详情 | |
| (III) | 19142 | 4-chloro-7-fluoro-6-nitroquinazoline | C8H3ClFN3O2 | 详情 | 详情 | |
| (IV) | 19136 | 3-bromoaniline; 3-bromophenylamine; 3-bromobenzenamine | 591-19-5 | C6H6BrN | 详情 | 详情 |
| (V) | 19144 | N-(3-bromophenyl)-N-(7-fluoro-6-nitro-4-quinazolinyl)amine; N-(3-bromophenyl)-7-fluoro-6-nitro-4-quinazolinamine | C14H8BrFN4O2 | 详情 | 详情 | |
| (VI) | 19145 | 3-(4-Morpholinyl)-1-propanol sodium salt | C7H14NNaO2 | 详情 | 详情 | |
| (VII) | 19146 | N-(3-bromophenyl)-7-[3-(4-morpholinyl)propoxy]-6-nitro-4-quinazolinamine; N-(3-bromophenyl)-N-[7-[3-(4-morpholinyl)propoxy]-6-nitro-4-quinazolinyl]amine | C21H22BrN5O4 | 详情 | 详情 | |
| (VIII) | 19147 | N(4)-(3-bromophenyl)-7-[3-(4-morpholinyl)propoxy]-4,6-quinazolinediamine; N-[6-amino-7-[3-(4-morpholinyl)propoxy]-4-quinazolinyl]-N-(3-bromophenyl)amine | C21H24BrN5O2 | 详情 | 详情 | |
| (IX) | 19139 | acrylic acid | 79-10-7 | C3H4O2 | 详情 | 详情 |