CHIR-200131

Chemical Name: 4-Amino-3-[5-[3(S)-(dimethylamino)pyrrolidin-1-yl]benzimidazol-2-yl]-1,2-dihydroquinolin-2-one
项目整合开发状态: Preclinical
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)