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【结 构 式】

【分子编号】61518

【品名】4-(3-chloro-4-fluoroanilino)-7-ethoxy-6-nitro-3-quinolinecarbonitrile

【CA登记号】

【 分 子 式 】C18H12ClFN4O3

【 分 子 量 】386.7695432

【元素组成】C 55.9% H 3.13% Cl 9.17% F 4.91% N 14.49% O 12.41%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VII)

The condensation of 3-ethoxy-4-nitroaniline (I) with 2-(ethoxymethylene)cyanacetic acid ethyl ester (II) in refluxing toluene gives the adduct (III), which is further cyclized in Dowtherm at 258 C to yield 7-ethoxy-6-nitro-4-oxo-1,4-dihydroquinoline-3-carbonitrile (IV). The reaction of (IV) with refluxing POCl3 affords the 4-chloroquinoline (V), which is condensed with 3-chloro-4-fluoroaniline (VI) in refluxing isopropanol to provide the secondary amine (VII). The reduction of the nitro group of (VII) with Fe and NH4Cl in refluxing methanol/water gives the corresponding amino derivative (VIII), which is condensed with the acid chloride (IX) by means of t-BuOCOCl and NMM in THF to yield the amide (X). Finally, this compound is treated with dimethylamine in THF to afford the target quinoline-3-carbonitrile.

1 Wissner, A.; Overbeek, E.; Reich, M.F.; Floyd, B.; Johnson, B.D.; Mamuya, N.; Rosfjord, E.C.; Discafani, C.; Davis, R.; Shi, X.; Rabindran, S.K.; Gruber, B.C.; Ye, F.; Hallett, W.A.; Nilakantan, R.; Shen, R.; Wang, Y.-F.; Greenberger, L.M.; Tsou, H.-R.; Synthesis and structure-activity relationships of 6,7-disubstituted 4-anilinoquinoline-3-carbonitriles. The design of an orally active, irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and the human epi. J Med Chem 2003, 46, 1, 49.
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) 61513 3-ethoxy-4-nitroaniline; 3-ethoxy-4-nitrophenylamine C8H10N2O3 详情 详情
(II) 61514 ethyl (Z)-2-cyano-3-propoxy-2-propenoate C9H13NO3 详情 详情
(III) 61515 ethyl (E)-2-cyano-3-(3-ethoxy-4-nitroanilino)-2-propenoate C14H15N3O5 详情 详情
(IV) 61516 7-ethoxy-6-nitro-4-oxo-1,4-dihydro-3-quinolinecarbonitrile C12H9N3O4 详情 详情
(V) 61517 4-chloro-7-ethoxy-6-nitro-3-quinolinecarbonitrile C12H8ClN3O3 详情 详情
(VI) 18688 3-Chloro-4-fluorophenylamine; 3-Chloro-4-fluoroaniline 367-21-5 C6H5ClFN 详情 详情
(VII) 61518 4-(3-chloro-4-fluoroanilino)-7-ethoxy-6-nitro-3-quinolinecarbonitrile C18H12ClFN4O3 详情 详情
(VIII) 61519 6-amino-4-(3-chloro-4-fluoroanilino)-7-ethoxy-3-quinolinecarbonitrile C18H14ClFN4O 详情 详情
(IX) 50564 (E)-4-bromo-2-butenoyl chloride C4H4BrClO 详情 详情
(X) 61520 (E)-4-bromo-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxy-6-quinolinyl]-2-butenamide C22H17BrClFN4O2 详情 详情
Extended Information