T-1032

2-(4-氨基苯基)-1-氧基-7-(吡啶-2-甲氧基)-4-(3,4,5-三甲氧基苯基)-1,2-二氢异喹啉-3-羧酸甲酯硫酸盐 2-(4-氨基苯基)-1,2-二氢-1-氧代-7-(2-吡啶甲氧基)-4-(3,4,5-三甲氧基苯基)-3-异喹啉羧酸甲基酯二盐酸 Chemical Name: 2-(4-Aminophenyl)-1-oxo-7-(pyridin-2-ylmethoxy)-4-(3,4,5-trimethoxyphenyl)-1,2-dihydroisoquinoline-3-carboxylic acid methyl ester sulfate
CAS No. 212500-03-3, 212498-37-8 (diHCl), 212500-05-5 (dimethanesulfonate), 212500-02-2 (free base)
项目整合开发状态: Preclinical
项目研究机构: Tanabe Seiyaku (Originator)
合成路线:Lithiation of 5-benzyloxy-2-bromobenzaldehyde dimethyl acetal (I),followed by addition to N,N-dimethyl-3,4,5-trimethoxybenzamide (II),gave rise to benzophenone (III).After acetal hydrolysis using an acidic ion exchange resin,the resulting aldehyde (IV) was oxidized to carboxylic acid (V) by means of sodium chlorite.Condensation of this keto acid (V) with diethyl bromomalonate (VI),followed by acidic treatment,furnished the isocoumarin derivative (VII).Subsequent addition of water to the double bond upon treatment with NaOH in aqueous methanol produced (VIII).This compound was condensed with N-Boc-p-phenylenediamine (IX) in the presence of N-methylmorpholine in hot 1,3-dimethyl-2-imidazolinone to afford the isoquinolinone (X).The methyl ester (XI) was prepared by reaction of carboxylic acid (X) with iodomethane and K2CO3.

合成路线:Hydrogenolytic removal of the O-benzyl group provided phenol (XII),which was subsequently alkylated with 2-picolyl chloride (XIII) to produce ether (XIV).The Boc protecting group of (XIV) was finally cleaved by treatment with HCl in EtOAc.