PD-205520

Chemical Name: N-[4-(3-Chloro-4-fluorophenylamino)pyrido[3,4-d]pyrimidin-6-yl]-5-(4-methylpiperazin-1-yl)-2-pentynamide hydrochloride
CAS No. 198960-77-9 (free base)
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator)
合成路线:Coupling of chloroquinazoline (I) with 3-bromoaniline (II) in refluxing isopropanol yielded anilinoquinazoline (III).The nitro group was then reduced with Fe dust and AcOH in aqueous ethanol to give amine (IV).Finally,condensation with acrylic acid (V) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.HCl (EDC) in DMF provided the target acrylamide.

合成路线:Nitration of quinazolinone (I) with fuming HNO3 in H2SO4 at 100 C gave a mixture of 6-nitro and 8-nitroquinazolines,from which the desired 6-isomer was isolated by recrystallization from AcOH.Subsequent treatment with refluxing SOCl2 and a catalytic amount of DMF gave chloride (III),which was condensed with 3-bromoaniline (IV) in isopropanol to afford anilinoquinazoline (V).Reaction with sodium alkoxide (VI) in refluxing THF provided ether (VII).Then,the nitro group was reduced with Fe dust and AcOH in aqueous ethanol to give amine (VIII).Finally,condensation with acrylic acid (X) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.HCl (EDC) in DMF yielded the target acrylamide.

合成路线:The title amide was prepared by coupling of 6-amino-4-(3-chloro-4-fluorophenylamino)pyrido[3,4-d]pyrimidine (I) with 5-(4-methyl-1-piperazinyl)-2-pentynoic acid (II) in the presence of EDC.