Droloxifene, FK-435, K-060, K-21060E
屈洛昔芬 枸橼酸屈洛昔芬 Chemical Name: (E)-3-[1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-phenyl-1-butenyl]phenol; (E)-1-[4'-(2-Dimethylaminoethoxy)phenyl]-1-(3'-hydroxyphenyl)-2-phenylbut-1-ene; (E)-alpha-[p-[2-(Dimethylamino)ethoxy]phenyl]-alpha'-ethyl-3-stilbenol
CAS No. 82413-20-5, 97752-20-0 (citrate (1:1)), 83647-28-3 (HCl)
项目整合开发状态: Discontinued
项目研究机构: Fujisawa (Originator), Fujisawa Deutschland (Originator), Pfizer (Licensee)
合成路线:The reaction of 1-(4-methoxyphenyl)-2-phenylethan-1-one (I) with ethyl bromide (A) gave (II) in nearly quantitative yield.Demethoxylation of (II) with pyridine hydrochloride gave (III) in about 70% yield.Treatment of (III) with dimethylaminoethyl chloride (B) gave (IV) in more than 60% yield.Reaction of (IV) with 3'-(2-tetrahydropyranyloxy)phenylmagnesium bromide (C) gave (V) in about 60% yield.Refluxing a solution of (V) in ethanolic hydrochloric acid gave the stereoisomeric E- and Z-mixture (VIa,VIb) of the hydrochloric salt.Fractional crystallization of the mixture in methanol/ether yielded the pure hydrochloric salt of the E-isomer in 48% yield.Conversion of the hydrochloric salt into the free base and treatment of the latter with citric acid yielded the appropriate K-21060E citrate.
📌 参考资料/链接：
参考文献标题:1,1,2-triphenylbut-1-ene derivatives
文献作者:Schickaneder,H.; Ler,R.; Grill,H.(Klinge Pharma GmbH)
参考来源:DE 3046719; EP 0054168; US 5047431
📄 详细内容
合成路线:The reaction of 1-(4-methoxyphenyl)-2-phenylethan-1-one (I) with ethyl bromide (A) gave (II) in nearly quantitative yield.Demethoxylation of (II) with pyridine hydrochloride gave (III) in about 70% yield.Treatment of (III) with dimethylaminoethyl chloride (B) gave (IV) in more than 60% yield.Reaction of (IV) with 3'-(2-tetrahydropyranyloxy)phenylmagnesium bromide (C) gave (V) in about 60% yield.Refluxing a solution of (V) in ethanolic hydrochloric acid gave the stereoisomeric E- and Z-mixture (VIa,VIb) of the hydrochloric salt.Fractional crystallization of the mixture in methanol/ether yielded the pure hydrochloric salt of the E-isomer in 48% yield.Conversion of the hydrochloric salt into the free base and treatment of the latter with citric acid yielded the appropriate K-21060E citrate.
参考文献标题:K-21060 E
文献作者:Ler,R.; Seibel,K.; Janiak,P.-St.
参考来源:Drugs Fut 1984,9(3),186