PD-0199646

Chemical Name: 6-[3(S)-Aminopyrrolidin-1-yl]-8-bromo-5-fluoro-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione
项目整合开发状态: Biological Testing
项目研究机构: Naeja (Originator), Pfizer (Originator)
合成路线:Diazotation of 3-amino-6-nitro-1,8-naphthalic anhydride (I) in the presence of pyridine hydrofluoride afforded the fluoro derivative (II).This was brominated to (III) using Br2 and Ag2SO4 and its nitro group was subsequently reduced to amine (IV) with SnCl2.Sandmeyer reaction of amine (IV) in the presence of CuBr furnished the dibromo anhydride (V),which was treated with O-tert-butylhydroxylamine,yielding the N-tert-butoxy imide (VI).Regioselective displacement of one bromide group of (VI) with (S)-3-(Boc-amino)pyrrolidine (VII) gave rise to the protected pyrrolidinyl derivative (VIII).Finally,the tert-butyl protecting groups of (VIII) were removed by acidic treatment to produce the title compound.