DuP-860

Chemical Name: 3-(2-Chlorophenyl)-2-(4-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)-3-buten-2-ol methanesulfonate; alpha-(4-Chlorophenyl)-alpha-[1-(2-chlorophenyl)ethenyl]-1H-1,2,4-triazole-1-ethanol methanesulfonate
CAS No. 124669-21-2 (free base), 124669-22-3 (monoHCl), 124669-23-4 (mononitrate), 124669-25-6 (phosphate (1:1) salt), 124669-24-5 (sulfate (1:1) salt)
项目整合开发状态: Phase I
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:This compound can be obtained by two related ways:1) The reaction of alpha-bromo-2-chlorostyrene (I) with magnesium gives the corresponding magnesiane (II),which is condensed with alpha,4-dichloroacetophenone (III) yielding 3-(2-chlorophenyl-2-(4-chlorophenyl)-1,2-epoxy-3-butene (IV).Finally,this compound is treated with potassium 1,2,4-triazole (V).2) The reaction of 1-(2-chlorophenyl)-2-(4-chlorophenyl)-2,3-epoxy-1-propane (VI) with methyltriphenylphosphonium bromide and n-butyllithium gives epoxide (IV),already obtained.

合成路线:The intermediate epoxide (IV) was synthesized by two different procedures:1) The Grignard reagent (II),prepared from 1-bromo-2'-chlorostyrene (I) and Mg,was condensed with 2-chloro-2',4'-difluoroacetophenone (III) to afford epoxide (IV).2) Alternatively,Wittig reaction of epoxyketone (V) with methylenetriphenylphosphorane provided the target intermediate (IV).The title compound was then obtained by epoxide opening of (IV) with potassium triazole (VI) in DMF at 60 C,and was isolated as the methanesulfonate salt.