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【结 构 式】 
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【分子编号】47292 【品名】4-[(acetoxy)methyl]-3-(4-cyanobenzyl)-1-trityl-1H-imidazol-3-ium bromide 【CA登记号】 |
【 分 子 式 】C33H28BrN3O2 【 分 子 量 】578.50834 【元素组成】C 68.51% H 4.88% Br 13.81% N 7.26% O 5.53% |
合成路线1
该中间体在本合成路线中的序号：(XVI)Protection of 4-(hydroxymethyl)imidazole (XII) with chlorotriphenylmethane provided the 1-tritylimidazole (XIII). Acetylation of (XIII) with acetic anhydride in pyridine gave acetate ester (XIV). The imidazole ring of (XIV) was then alkylated with alpha-bromo-p-tolunitrile (XV) to yield the imidazolium salt (XVI), from which the N-trityl group was removed upon heating with MeOH. The resulting acetoxymethyl imidazole (XVII) was then hydrolyzed to alcohol (XVIII) using LiOH, and further Swern oxidation of (XVIII) furnished aldehyde (XIX). Finally, reductive condensation of aldehyde (XIX) with piperazinone (VIII) in the presence of sodium triacetoxyborohydride produced the title compound.
| 【1】 Anthony, N.J.; Ciccarone, T.M.; Gomez, R.P.; Hutchinson, J.H.; Williams, T.M.; Dinsmore, C.J.; Stokker, G.E. (Merck & Co., Inc.); Inhibitors of farnesyl-protein transferase. EP 0820445; JP 1998511098; US 5856326; WO 9630343 . |
| 【2】 Williams, T.M.; Dinsmore, C.J.; Hutchinson, J.H. (Merck & Co., Inc.); Inhibitors of prenyl-protein transferase. EP 1014984; WO 9909985 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 47289 | 1-(3-chlorophenyl)-2-piperazinone | C10H11ClN2O | 详情 | 详情 | |
| (XII) | 42116 | 1H-imidazol-5-ylmethanol | C4H6N2O | 详情 | 详情 | |
| (XIII) | 38392 | (1-trityl-1H-imidazol-4-yl)methanol | C23H20N2O | 详情 | 详情 | |
| (XIV) | 38391 | (1-trityl-1H-imidazol-4-yl)methyl acetate | C25H22N2O2 | 详情 | 详情 | |
| (XV) | 14200 | 4-(Bromomethyl)benzonitrile; alpha-Bromo-p-tolunitrile | 17201-43-3 | C8H6BrN | 详情 | 详情 |
| (XVI) | 47292 | 4-[(acetoxy)methyl]-3-(4-cyanobenzyl)-1-trityl-1H-imidazol-3-ium bromide | C33H28BrN3O2 | 详情 | 详情 | |
| (XVII) | 38390 | [1-(4-cyanobenzyl)-1H-imidazol-5-yl]methyl acetate | C14H13N3O2 | 详情 | 详情 | |
| (XVIII) | 38389 | 4-[[5-(hydroxymethyl)-1H-imidazol-1-yl]methyl]benzonitrile | C12H11N3O | 详情 | 详情 | |
| (XIX) | 38388 | 4-[(5-formyl-1H-imidazol-1-yl)methyl]benzonitrile | C12H9N3O | 详情 | 详情 |