新产品编号:2090331

Chemical Name: N-[2-[2-(4-Butylphenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-1-yl]ethyl]pyridine-3-carboxamide
项目整合开发状态: Preclinical
项目研究机构: AstraZeneca (Originator), Organon (Originator)
合成路线:Acylation of phenethylamine (III) with acid chloride (II),prepared from phthalimidopropionic acid (I) and SOCl2,gave amide (IV).Subsequent Bischler-Napieralski cyclization of amide (IV) in the presence of POCl3 and P2O5 produced the corresponding dihydroisoquinoline,which was isolated as the hydrochloride salt (V).Catalytic hydrogenation of (V) using PtO2 afforded the tetrahydroisoquinoline (VI).After protection of (VI) as the N-Boc derivative (VII),the primary amine (VIII) was liberated by phthaloyl group hydrazinolysis.Coupling of amine (VIII) with nicotinic acid (IX) employing EDC and HOBt yielded the nicotinamide compound (X).Subsequent acidic cleavage of the Boc protecting group of (X) provided amine (XI),which was finally acylated with 4-butylbenzenesulfonyl chloride (XII) in the presence of resin-bound piperidine to furnish the target sulfonamide.