PNU-181128

Chemical Name: N-(4-Chlorobenzyl)-4-hydroxy-6-(3-hydroxy-1-propynyl)quinoline-3-carboxamide
项目整合开发状态: Biological Testing
项目研究机构: Pfizer (Originator)
合成路线:The condensation of 2-fluoroaniline (I) with diethyl ethoxymethylene malonate (II) at 130 C afforded enamine (III),which was further cyclized to ethyl 8-fluoro-4-hydroxy-3-quinolinecarboxylate (IV) upon heating at 250 C.Condensation of (III) with neat 4-chlorobenzylamine (V) then provided the desired carboxamide.

合成路线:The condensation between 4-iodoaniline (I) and diethyl ethoxymethylenemalonate (II) at 130 C,followed by cyclization in diphenyl ether at 250 C,furnished ethyl 4-hydroxy-6-iodoquinoline-3-carboxylate (III).Subsequent reaction of ester (III) with 4-chlorobenzylamine (IV) at 180 C produced the corresponding amide (V).Finally,coupling of (V) with propargyl alcohol (VI) in the presence of CuI and palladium catalyst afforded the desired (hydroxypropynyl)quinoline.