CHF-4227
Chemical Name: 3-(4-Methoxyphenyl)-4-[4-[2-(1-piperidinyl)ethoxy]benzyl]-2H-1-benzopyran-7-ol hydrochloride
项目整合开发状态: Phase I
项目研究机构: Chiesi (Originator)
合成路线:The title compound is synthesized starting from the natural isoflavone formononetin (I).Esterification of (I) with pivaloyl chloride (II) affords pivalate (III).Catalytic hydrogenation of (III) in the presence of Pd/BaSO4 leads to the chromane derivative (IV).The Grignard reagent (VI),prepared from 4-(benzyloxy)benzyl chloride (V),is then condensed with ketone (IV) to furnish the tertiary alcohol (VII).The O-benzyl protecting group of (VII) is then removed by catalytic hydrogenolysis to afford phenol (VIII).Alkylation of (VIII) with N-(2-chloroethyl)piperidine (IX) and K2CO3,with simultaneous pivalate ester hydrolysis,leads to the piperidylethyl ether (X).The tertiary alcohol of (X) is finally dehydrated by means of HCl in acetonitrile to provide the target compound (1,2).
📌 参考资料/链接：
参考文献标题:2H-1-Benzopyran derivs.,processes for their preparation and pharmaceutical compsns.thereof
文献作者:Delcanale,M.; Civelli,M.; Armani,E.; Amari,G.; Galbiati,E.(Chiesi Farmaceutici SpA)
参考来源:EP 1229036; EP 1281710; EP 1355906; WO 0259113
📄 详细内容
合成路线:The title compound is synthesized starting from the natural isoflavone formononetin (I).Esterification of (I) with pivaloyl chloride (II) affords pivalate (III).Catalytic hydrogenation of (III) in the presence of Pd/BaSO4 leads to the chromane derivative (IV).The Grignard reagent (VI),prepared from 4-(benzyloxy)benzyl chloride (V),is then condensed with ketone (IV) to furnish the tertiary alcohol (VII).The O-benzyl protecting group of (VII) is then removed by catalytic hydrogenolysis to afford phenol (VIII).Alkylation of (VIII) with N-(2-chloroethyl)piperidine (IX) and K2CO3,with simultaneous pivalate ester hydrolysis,leads to the piperidylethyl ether (X).The tertiary alcohol of (X) is finally dehydrated by means of HCl in acetonitrile to provide the target compound (1,2).
参考文献标题:Synthesis and pharmacological activity of CHF 4227,one of the most potent in vitro and in vivo SERMs till new discovered
文献作者:Ghirardi,S.; Armani,E.; Amari,G.; Delcanale,M.; Civelli,M.; Caruso,P.; Galbiati,E.
参考来源:Drugs Fut 2002,27(Suppl.A),