Zelandopam hydrochloride, MYD-37, YM-435
7,8-异喹啉二醇,4-(3,4-二羟基苯基)-1,2,3,4-四氢盐-,盐酸盐(1:1),(4S)- (4S)-4-(3,4-二羟基苯基)-1,2,3,4-四氢异喹啉-7,8-二醇盐酸盐 4-(3,4-二羟基苯基)-1,2,3,4-四氢-7,8-异喹啉二醇Chemical Name: (-)-(S)-4-(3,4-Dihydroxyphenyl)-7,8-dihydroxy-1,2,3,4-tetrahydroisoquinoline hydrochloride hydrate; (-)-(S)-4-(3,4-Dihydroxyphenyl)-1,2,3,4-tetrahydro-7,8-isoquinolinediol hydrochloride hydrate
CAS No. 138086-00-7 (anhydrous), 139233-53-7 (anhydrous free base), 119085-25-5 (anhydrous free base, non-specified stereoch.), 119086-13-4 (anhydrous HBr salt, non-specified stereoch.)
项目整合开发状态: Phase II
项目研究机构: Yamanouchi (Originator), Mochida (Licensee)
合成路线:The reductocondensation of 2,3-dimethoxybenzaldehyde (I) with 2-(3,4-dimethoxyphenyl)-2-hydroxyethylamine (II) by means of NaBH4 in methanol gives N-(2,3-dimethoxybenzyl)-2-(3,4-dimethoxyphenyl)-2-hydroxyethylamine (III),which is cyclized by means of H2SO4 in TFA,followed by an azeotropic distillation with toluene to yield the tetrahydroisoquinoline (IV).Finally,this compound is demethylated by means of refluxing 48 % HBr to provide the target racemic tetrahydroisoquinoline.
📌 参考资料/链接：
参考文献标题:Substd.tetrahydroisoquinoline cpds.,their production,and pharmaceutical compsns.containing them
文献作者:Tanaka,A.; Fujikura,T.; Tsuzuki,R.; Yokota,M.; Yatsu,T.(Yamanouchi Pharmaceutical Co.,Ltd.)
参考来源:EP 0286293; EP 0399626; JP 1989199948; US 4876261; US 5079256
📄 详细内容
合成路线:Amino alcohol (III) was prepared from veratraldehyde (I) by addition of cyanotrimethylsilane,followed by borane reduction of the resultant cyanohydrin (II).Reductive condensation of amine (III) with 2,3-dimethoxybenzaldehyde (IV) gave the secondary amine (V).This was cyclized to the tetrahydroisoquinoline (VI) under acidic conditions.Resolution of the racemic (VI) by means of dibenzoyltartaric acid furnished the desired (S)-amine,which was further acylated with Ac2O to yield the chiral amide (VII).Demethylation of (VII) with boron tribromide afforded the tetrahydroxy compound (VIII).Finally,acetamide hydrolysis under acidic conditions yielded the title compound.
参考文献标题:Synthesis,resolution,and renal vasodilation activity of novel DA1 agonists: 4-(3,4-Dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline derivatives
文献作者:Anan,H.; Tanaka,A.; Tsuzuki,R.; Yokota,M.; Yatsu,T.; Honda,K.; Asano,M.; Fujita,S.; Furuya,T.; Fujikura,T.
参考来源:Chem Pharm Bull 1991,39(11),2910