GFKI-258, CHIR-258LC, CHIR-258
多韦替尼Chemical Name: 4-Amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one
CAS No. 405169-16-6
项目整合开发状态: Phase I
项目研究机构: Chiron (Originator)
合成路线:The cyclization of the phenylenediamine (I) with 3-ethoxy-3-iminopropionic acid ethyl ester (II) in refluxing ethanol gives the 2-(benzimidazol-2-yl)acetate (III),which is submitted to a new cyclization with 2-aminobenzonitrile (IV) by means of LiHMDS in THF to afford the target quinolinone.
合成路线:Reaction of 2,4-difluoronitrobenzene (I) with liquid ammonia gives rise to 5-fluoro-2-nitroaniline (II).Subsequent displacement of the remaining fluoride group of (II) with N-methylpiperazine (III) provides the piperazinyl aniline (IV).Catalytic hydrogenation of nitroaniline (IV) over Pd/C yields the phenylenediamine (V).This is then condensed with ethyl 3-ethoxy-3-iminopropanoate (VI) to produce benzimidazole (VII).Finally,reaction of the lithium enolate of benzimidazoleacetate (VII) with 2-amino-6-fluorobenzonitrile (VIII) furnishes the title quinolinone compound.(1,2)
📌 参考资料/链接：
参考文献标题:Quinolinone derivs.
文献作者:Harris,A.; Renhowe,P.; Machajewski,T.; Shafer,C.; Wernette-Hammond,M.-E.; Pecchi,S.; Taylor,C.; McCrea,B.; McBride,C.; Jazan,E.(Chiron Corp.)
参考来源:WO 0222598
📄 详细内容
合成路线:Reaction of 2,4-difluoronitrobenzene (I) with liquid ammonia gives rise to 5-fluoro-2-nitroaniline (II).Subsequent displacement of the remaining fluoride group of (II) with N-methylpiperazine (III) provides the piperazinyl aniline (IV).Catalytic hydrogenation of nitroaniline (IV) over Pd/C yields the phenylenediamine (V).This is then condensed with ethyl 3-ethoxy-3-iminopropanoate (VI) to produce benzimidazole (VII).Finally,reaction of the lithium enolate of benzimidazoleacetate (VII) with 2-amino-6-fluorobenzonitrile (VIII) furnishes the title quinolinone compound.(1,2)
参考文献标题:Quinolinone derivs.
文献作者:Renhowe,P.A.; Pecchi,S.; Taylor,C.; McBride,C.; Jazan,E.; Shafer,C.M.; Machajewski,T.D.; McCrea,W.R.Jr.(Chiron Corp.)
参考来源:US 2003028018; WO 0387095
产品链接: CAS No. 405169-16-6››