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【结 构 式】

【分子编号】31532

【品名】7-(benzyloxy)-N-(4-bromo-2-fluorophenyl)-6-methoxy-4-quinazolinamine; N-[7-(benzyloxy)-6-methoxy-4-quinazolinyl]-N-(4-bromo-2-fluorophenyl)amine

【CA登记号】

【 分 子 式 】C22H17BrFN3O2

【 分 子 量 】454.2984032

【元素组成】C 58.16% H 3.77% Br 17.59% F 4.18% N 9.25% O 7.04%

与该中间体有关的原料药合成路线共 2 条

合成路线1

该中间体在本合成路线中的序号:(VI)

Quinazolinone (III) was prepared by treatment of aminobenzamide (I) with Gold's reagent (II) in refluxing dioxan. Subsequent chlorination using thionyl chloride gave chloroquinazoline (IV). Nucleophilic displacement of the chlorine atom of (IV) with 4-bromo-2-fluoroaniline (V) yielded the anilinoquinazoline (VI). The benzyl group of (VI) was then cleaved with trifluoroacetic acid, and the resulting hydroxyquinazoline (VII) was finally coupled with (hydroxyethyl)triazole (VIII) using DEAD and PPh3 to furnish the title compound.

1 Thomas, A.P.; Johnstone, C.; Hennequin, L.F.; et al.; Design and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors. J Med Chem 1999, 42, 26, 5369.
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) 31528 2-amino-4-(benzyloxy)-5-methoxybenzamide C15H16N2O3 详情 详情
(II) 31529 N-([[(E)-(dimethylamino)methylidene]amino]methylene)-N-methylmethanaminium C6H14N3 详情 详情
(III) 31530 7-(benzyloxy)-6-methoxy-4(3H)-quinazolinone C16H14N2O3 详情 详情
(IV) 31531 benzyl 4-chloro-6-methoxy-7-quinazolinyl ether; 7-(benzyloxy)-4-chloro-6-methoxyquinazoline C16H13ClN2O2 详情 详情
(V) 14723 4-Bromo-2-fluorophenylamine; 4-Bromo-2-fluoroaniline 367-24-8 C6H5BrFN 详情 详情
(VI) 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
(VII) 31533 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-quinazolinol C15H11BrFN3O2 详情 详情
(VIII) 31534 2-(1H-1,2,3-triazol-1-yl)-1-ethanol C4H7N3O 详情 详情

合成路线2

该中间体在本合成路线中的序号:(VII)

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
Extended Information