【药物名称】RWJ-52353
化学结构式(Chemical Structure):
参考文献No.40816
标题:4-Thionaphthyl-1H-imidazoles with alpha-2-adrenergic activity
作者:Jetter, M.C.; Baxter, E.W.; McDonnell, M.; Ross, T.M.; Reitz, A.B.; Boyd, R.E. (Ortho-McNeil Pharmaceutical, Inc.)
来源:WO 9951593
合成路线图解说明:

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No.527592
标题:Synthesis, alpha2 adrenergic receptor binding affinity and in vivo activity of certain imidazole-substituted bicyclic thiophenes
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.
来源:217th ACS Natl Meet (March 21 1999, Anaheim) 1999,Abst MEDI 111
合成路线图解说明:

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No.570791
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
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.
来源:J Med Chem 2000,43(7),1423
合成路线图解说明:

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.

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