4-iodo-1-trityl-1H-imidazole -Drug Synthesis Database

【结构式】

【分子编号】30216

【品名】4-iodo-1-trityl-1H-imidazole

【CA登记号】

【分子式】C₂₂H₁₇IN₂

【分子量】436.29493

【元素组成】C 60.56% H 3.93% I 29.09% N 6.42%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(I)

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.

参考文献中间体

合成目标

【1】 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.; Synthesis, alpha2 adrenergic receptor binding affinity and in vivo activity of certain imidazole-substituted bicyclic thiophenes. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 111.
【2】 Ross, T.M.; Martinez, R.P.; Jetter, M.C.; McDonnell, M.E.; Boyd, R.E.; Raffa, R.B.; Codd, E.E.; Reitz, A.B.; Lewis, M.A.; Connelly, C.D.; 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. J Med Chem 2000, 43, 7, 1423.
【3】 Jetter, M.C.; Baxter, E.W.; McDonnell, M.; Ross, T.M.; Reitz, A.B.; Boyd, R.E. (Ortho-McNeil Pharmaceutical, Inc.); 4-Thionaphthyl-1H-imidazoles with alpha-2-adrenergic activity. WO 9951593 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(Va)	30219	4-(tributylstannyl)-1-trityl-1H-imidazole		C₃₄H₄₄N₂Sn	详情	详情
(Vb)	30220	chloro(1-trityl-1H-imidazol-4-yl)magnesium		C₂₂H₁₇ClMgN₂	详情	详情
(I)	30216	4-iodo-1-trityl-1H-imidazole		C₂₂H₁₇IN₂	详情	详情
(II)	30217	bromo(1-trityl-1H-imidazol-4-yl)magnesium		C₂₂H₁₇BrMgN₂	详情	详情
(III)	11045	6,7-Dihydro-1-benzothiophen-4(5H)-one; 4-Keto-4,5,6,7-tetrahydrothianaphthene; Tetrahydrobenzo(b)thiophene-4-one	13414-95-4	C₈H₈OS	详情	详情
(IV)	30218	4-(1-trityl-1H-imidazol-4-yl)-4,5,6,7-tetrahydro-1-benzothiophen-4-ol		C₃₀H₂₆N₂OS	详情	详情
(VI)	30221	6,7-dihydro-1-benzothiophen-4-yl trifluoromethanesulfonate		C₉H₇F₃O₃S₂	详情	详情
(VII)	30222	4-(6,7-dihydro-1-benzothiophen-4-yl)-1-trityl-1H-imidazole		C₃₀H₂₄N₂S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

Metalation of 1-trityl-4-iodoimidazole (VI) with ethylmagnesium bromide, followed by addition to 4-cyanobenzaldehyde (VII) gives rise to the carbinol (VIII), which is further reduced to the diaryl methane (IX) employing triibutyltin hydride in the presence of AIBN. Trimethylaluminium-catalyzed coupling between nitrile (IX) and amine (V) provides amidine (X). The N-trityl group of (X) is finally removed under acidic conditions to furnish the title compound.

参考文献中间体

合成目标

【1】 Tom, W.; Aslanian, R.; West, R.; Shih, N.-Y.; Piwinski, J.J.; She, S.; Williams, S.M.; Design and synthesis of novel dual histamine H1/H3 receptor antagonists based on the H1 receptor antagonist chlorpheniramine. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 63.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	57813	3-(4-chlorophenyl)-3-(2-pyridinyl)propylamine; 3-(4-chlorophenyl)-3-(2-pyridinyl)-1-propanamine		C₁₄H₁₅ClN₂	详情	详情
(VI)	30216	4-iodo-1-trityl-1H-imidazole		C₂₂H₁₇IN₂	详情	详情
(VII)	17552	4-formylbenzonitrile; 4-Cyanobenzaldehyde	105-07-7	C₈H₅NO	详情	详情
(VIII)	57814	4-[hydroxy(1-trityl-1H-imidazol-4-yl)methyl]benzonitrile		C₃₀H₂₃N₃O	详情	详情
(IX)	57815	4-[(1-trityl-1H-imidazol-4-yl)methyl]benzonitrile		C₃₀H₂₃N₃	详情	详情
(X)	57816	N-[3-(4-chlorophenyl)-3-(2-pyridinyl)propyl]-4-[(1-trityl-1H-imidazol-4-yl)methyl]benzenecarboximidamide		C₄₄H₃₈ClN₅	详情	详情

Extended Information