PD-172803

Chemical Name: 8-Isopropyl-2-[4-(4-methyl-1-piperazinyl)phenylamino]pyrido[2,3-d]pyrimidin-7(8H)-one
CAS No. 211245-21-5
项目整合开发状态: Biological Testing
项目研究机构: Pfizer (Originator)
合成路线:Treatment of ethyl 4-chloro-2-(methylsulfanyl)pyrimidine-5-carboxylate (I) with ammonium hydroxide provided the aminopyrimidine (II).After reduction of the ethyl ester (II) to alcohol (III) with LiAlH4,oxidation with MnO2 in chloroform yielded aldehyde (IV).Wittig condensation of (IV) with phosphorane (V) afforded the unsaturated ester (VI),which was cyclized to the pyridopyrimidinone (VII) upon treatment with DBU in diisopropylethylamine.Then,alkylation of (VII) with 2-iodopropane in the presence of NaH in DMF gave rise to the 8-isopropyl pyridopyrimidinone (VIII).Subsequent oxidation of the sulfide group of (VIII) to sulfoxide (X) was carried out employing trans-2-(phenylsulfonyl)-3-phenyloxaziridine (IX).Finally,displacement of the methylsulfinyl group of (X) with 4-(4-methylpiperazin-1-yl)aniline (XI) at 175 C yielded the title compound.