RWJ-52353

合成路线:This compound has been obtained by two different ways:1) The reaction of 4-iodo-1-tritylimidazole (I) with ethylmagnesium bromide produced the Grignard reagent (II).Subsequent addition of (II) to 4,5,6,7-tetrahydrobenzo[b]thiophen-4-one (III) afforded the tertiary alcohol (IV).Finally,acidic treatment of (IV) with methanolic HCl effected both alcohol dehydration and trityl group cleavage to yield the title compound.2) The reaction of 4-iodo-1-tritylimidazole (I) first with ethylmagnesium bromide to give the Grignard reagent (II) and then with either Bu3SnCl or ZnCl2 gave the respective tin- or zinc-organometallic reagents (V).4,5,6,7-Tetrahydrobenzo[b]thiophen-4-one (III) was then converted to the corresponding enol triflate (VI) by means of LDA and N-phenyltrifluoromethanesulfonimide (1) or trifluoromethanesulfonic anhydride.Subsequent coupling of (VI) with organometallic (V) in the presence of a palladium catalyst and LiCl in dioxane furnished 4-(1-tritylimidazol-4-yl)-6,7-dihydrobenzo[b]thiophene (VII),which was finally treated with methanolic HCl to perform the cleavage of the trityl group and yield the target compound.

参考文献标题:Synthesis,alpha2 adrenergic receptor binding affinity and in vivo activity of certain imidazole-substituted bicyclic thiophenes
文献作者:Martinez,R.P.; Baxter,M.; McDonnell,M.E.; Boyd,R.E.; Connelly,C.D.; Codd,E.E.; Lewis,M.E.; Reitz,A.B.; Jetter,M.C.; Ross,T.M.
参考来源:217th ACS Natl Meet (March 21 1999,Anaheim) 1999,Abst MEDI 111


合成路线:This compound has been obtained by two different ways:1) The reaction of 4-iodo-1-tritylimidazole (I) with ethylmagnesium bromide produced the Grignard reagent (II).Subsequent addition of (II) to 4,5,6,7-tetrahydrobenzo[b]thiophen-4-one (III) afforded the tertiary alcohol (IV).Finally,acidic treatment of (IV) with methanolic HCl effected both alcohol dehydration and trityl group cleavage to yield the title compound.2) The reaction of 4-iodo-1-tritylimidazole (I) first with ethylmagnesium bromide to give the Grignard reagent (II) and then with either Bu3SnCl or ZnCl2 gave the respective tin- or zinc-organometallic reagents (V).4,5,6,7-Tetrahydrobenzo[b]thiophen-4-one (III) was then converted to the corresponding enol triflate (VI) by means of LDA and N-phenyltrifluoromethanesulfonimide (1) or trifluoromethanesulfonic anhydride.Subsequent coupling of (VI) with organometallic (V) in the presence of a palladium catalyst and LiCl in dioxane furnished 4-(1-tritylimidazol-4-yl)-6,7-dihydrobenzo[b]thiophene (VII),which was finally treated with methanolic HCl to perform the cleavage of the trityl group and yield the target compound.
参考文献标题:alpha2 Adrenoceptor agonists as potential analgesic agents.2.Discovery of 4-(4-imidazo)-1,3-dimethyl-6,7-dihydrothianaphthene as a high-affinity ligand for the alpha2D adrenergic receptor
文献作者:Ross,T.M.; Jetter,M.C.; McDonnell,M.E.; Boyd,R.E.; Connelly,C.D.; Martinez,R.P.; Lewis,M.A.; Codd,E.E.; Raffa,R.B.; Reitz,A.B.
参考来源:J Med Chem 2000,43(7),1423