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【结 构 式】 
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【分子编号】49850 【品名】N-(4-bromo-2-fluorophenyl)-6-methoxy-7-(4-piperidinylmethoxy)-4-quinazolinamine; N-(4-bromo-2-fluorophenyl)-N-[6-methoxy-7-(4-piperidinylmethoxy)-4-quinazolinyl]amine 【CA登记号】 |
【 分 子 式 】C21H22BrFN4O2 【 分 子 量 】461.3338432 【元素组成】C 54.67% H 4.81% Br 17.32% F 4.12% N 12.14% O 6.94% |
合成路线1
该中间体在本合成路线中的序号：(X)Nucleophilic substitution of the chloroquinazoline (V) with 4-bromo-2-fluoroaniline (VI) in refluxing isopropanol provided the anilino quinazoline (VII). Subsequent cleavage of the benzyl ether group of (VII) by treatment with hot trifluoroacetic acid gave phenol (VIII), which was condensed with tosylate (IV) to furnish the ether adduct (IX). Acid deprotection of the N-Boc group of (IX) gave piperidine (X). Finally, reductive methylation of (X) using formaldehyde and sodium cyanoborohydride yielded the corresponding N-methyl piperidine.
| 【1】 Hennequin, L.F.A.; Stokes, E.S.E.; Thomas, A.P. (AstraZeneca AB; AstraZeneca plc); Quinazoline derivs. as VEGF inhibitors. WO 0132651 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 49848 | tert-butyl 4-([[(4-methylphenyl)sulfonyl]oxy]methyl)-1-piperidinecarboxylate | C18H27NO5S | 详情 | 详情 | |
| (V) | 31531 | benzyl 4-chloro-6-methoxy-7-quinazolinyl ether; 7-(benzyloxy)-4-chloro-6-methoxyquinazoline | C16H13ClN2O2 | 详情 | 详情 | |
| (VI) | 14723 | 4-Bromo-2-fluorophenylamine; 4-Bromo-2-fluoroaniline | 367-24-8 | C6H5BrFN | 详情 | 详情 |
| (VII) | 31532 | 7-(benzyloxy)-N-(4-bromo-2-fluorophenyl)-6-methoxy-4-quinazolinamine; N-[7-(benzyloxy)-6-methoxy-4-quinazolinyl]-N-(4-bromo-2-fluorophenyl)amine | C22H17BrFN3O2 | 详情 | 详情 | |
| (VIII) | 31533 | 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-quinazolinol | C15H11BrFN3O2 | 详情 | 详情 | |
| (IX) | 49849 | tert-butyl 4-([[4-(4-bromo-2-fluoroanilino)-6-methoxy-7-quinazolinyl]oxy]methyl)-1-piperidinecarboxylate | C26H30BrFN4O4 | 详情 | 详情 | |
| (X) | 49850 | N-(4-bromo-2-fluorophenyl)-6-methoxy-7-(4-piperidinylmethoxy)-4-quinazolinamine; N-(4-bromo-2-fluorophenyl)-N-[6-methoxy-7-(4-piperidinylmethoxy)-4-quinazolinyl]amine | C21H22BrFN4O2 | 详情 | 详情 |