Panomifene, EGIS-5650, GYKI-13504
帕诺米芬Chemical Name: (E)-2-[[2-[4-(3,3,3-Trifluoro-1,2-diphenyl-1-propenyl)phenoxy]ethyl]amino]ethanol; (E)-1,2-Diphenyl-1-[4-[(2-hydroxyethylamino)ethoxy]phenyl]-3,3,3-trifluoro-1-propene
CAS No. 77599-17-8, 77600-10-3
项目整合开发状态: Phase I
项目研究机构: Egis (Originator), Fujimoto (Licensee)
合成路线:The synthesis of GYKI-13504 is as follows:Trifluoroacetophenone (I) is reacted with triphenylbenzyl phosphonium chloride (II) in the presence of sodium methylate and this reaction yields stilbene (III).Stilbene (III) is then hydrogenized in the presence of charcoal palladium catalyzer and the yielded propane derivative (IV) is brominated with 1,2-dibromoethane.The brominated compound (V) is reacted with anizole (A) according to the Friedel Crafts' reaction.The yield (VI) is treated with pyridine hydrochloride and the phenol derivative (VII) is reacted with 2-chloroethanol tosylate (VIII) in the presence of potassium hydroxide.The chloroethoxy (IX) is treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and the (E)-isomer (X) is obtained with fractionated crystallization.This latter product is reacted with 2-aminoethanol (B) to obtain the end product GYKI-13504.
📌 参考资料/链接：
参考文献标题:1,1,2-Triphenylpropane and -propene derivatives
文献作者:Abraham,G.; Horvh,T.; Toldy,L.; Borvendeg,J.; Csyl,E.; Kiss,E.; Szente,I.; Tory,K.(Egis Pharmaceuticals Ltd.)
参考来源:AT 368989; BE 0884716; DD 152536; ES 494286; GB 2058061; GR 69821; HU 18253.
📄 详细内容
合成路线:The synthesis of GYKI-13504 is as follows:Trifluoroacetophenone (I) is reacted with triphenylbenzyl phosphonium chloride (II) in the presence of sodium methylate and this reaction yields stilbene (III).Stilbene (III) is then hydrogenized in the presence of charcoal palladium catalyzer and the yielded propane derivative (IV) is brominated with 1,2-dibromoethane.The brominated compound (V) is reacted with anizole (A) according to the Friedel Crafts' reaction.The yield (VI) is treated with pyridine hydrochloride and the phenol derivative (VII) is reacted with 2-chloroethanol tosylate (VIII) in the presence of potassium hydroxide.The chloroethoxy (IX) is treated with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and the (E)-isomer (X) is obtained with fractionated crystallization.This latter product is reacted with 2-aminoethanol (B) to obtain the end product GYKI-13504.
参考文献标题:GYKI-13504
文献作者:Borvend,J.
参考来源:Drugs Fut 1985,10(5),395.
产品链接: CAS No. 77599-17-8››