新产品编号:1963771
Chemical Name: 1-(3-Chlorophenyl)-4-[1-[4'-(trifluoromethyl)biphenyl-4-ylmethyl]-1H-imidazol-5-ylmethyl]piperazin-2-one
项目整合开发状态: Preclinical
项目研究机构: Merck & Co. (Originator)
合成路线:3-Chloroaniline (I) was acylated with chloroacetyl chloride (II) in isopropyl acetate.The resulting chloroacetanilide (III) was condensed with ethanolamine (IV) to yield the (hydroxyethyl)glycinamide (V).Cyclization of (V) to produce the piperazinone (VI) was then effected by treatment with di-tert-butyl azodicarboxylate and tributylphosphine.
合成路线:The mercaptoimidazole (IX) was prepared by condensation between 4-bromobenzylamine (VII),1,3-dihydroxyacetone (VIII) and potassium thiocyanate.Oxidative desulfuration of (IX) with hydrogen peroxide in acidic medium yielded imidazole (X).The biphenyl derivative (XII) was obtained by Suzuki coupling of aryl bromide (X) with 4-(trifluoromethyl)benzeneboronic acid (XI).Subsequent oxidation of the alcohol group of (XII) under Swern conditions gave aldehyde (XIII).Finally,reductive coupling of aldehyde (XIII) with piperazinone (VI) in the presence of sodium triacetoxyborohydride furnished the title compound.
📌 参考资料/链接：
参考文献标题:Biaryl inhibitors of prenyl-protein transferase
文献作者:Williams,T.M.(Merck & Co.,Inc.)
参考来源:WO 0075135
📄 详细内容
合成路线:The mercaptoimidazole (IX) was prepared by condensation between 4-bromobenzylamine (VII),1,3-dihydroxyacetone (VIII) and potassium thiocyanate.Oxidative desulfuration of (IX) with hydrogen peroxide in acidic medium yielded imidazole (X).The biphenyl derivative (XII) was obtained by Suzuki coupling of aryl bromide (X) with 4-(trifluoromethyl)benzeneboronic acid (XI).Subsequent oxidation of the alcohol group of (XII) under Swern conditions gave aldehyde (XIII).Finally,reductive coupling of aldehyde (XIII) with piperazinone (VI) in the presence of sodium triacetoxyborohydride furnished the title compound.
参考文献标题:Potent inhibitors of farnesyltransferase and geranylgeranyltransferase
文献作者:Kohl,N.E.; Nguyen,D.N.; Lobell,R.B.; Williams,T.M.; Heimbrook,D.C.; Buser,C.A.; Huber,H.E.; Stump,C.A.; Graham,S.L.
参考来源:221st ACS Natl Meet (April 1 2001,San Diego) 2001,Abst MEDI 56