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【结 构 式】 
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【分子编号】16489 【品名】[(2S,4S)-2-(4-chlorophenethyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl 4-methylbenzenesulfonate 【CA登记号】 |
【 分 子 式 】C23H25ClN2O5S 【 分 子 量 】476.98068 【元素组成】C 57.92% H 5.28% Cl 7.43% N 5.87% O 16.77% S 6.72% |
合成路线1
该中间体在本合成路线中的序号：(IX)Reaction of the Grignard reagent derived from 4-chlorobenzyl bromide (I) with allyl bromide (II) gives 4-(4-chlorophenyl)but-1-ene (III), which is epoxidized with peracetic acid in dichloromethane to yield 4-(4-chlorophenyl)-1,2-epoxybutane (IV). Opening of (IV) with the anion of imidazole (V) gives 1-[4-(4-chlorophenyl)-2-hydroxybutyl]imidazole (VI), which is oxidized under Swern conditions to 4-(4-chlorophenyl)-1-(1-imidazolyl)-2-butanone (VII). Ketone (VII) is then reacted with (S)-solketal tosylate [(S)-1,2-O-isopropylideneglycerol-3-O-tosylate] (VIII) in the presence of p-toluenesulfonic acid in toluene to give a mixture of stereoisomers, and (2S,4S)-cis-2-[2-(4-chlorophenyl)ethyl]-2-(imidazol-1-ylmethyl)-4-(p-toluenesulfonyloxy)methyl-1,3-dioxolane (IX) is then separated by crystallization. Finally, (IX) is treated with 4-aminothiophenol (X) in the presence of potassium carbonate in acetone.
| 【1】 Dyson, N.H.; Gardner, J.O.; Prince, A.; Kertesz, D.J. (Syntex (USA), Inc.); Process for preparing 1,3-dioxolane derivs. JP 1995508002; US 5208331 . |
| 【2】 Walker, K.A.; Burton, P.M.; Swinney, D.C. (Syntex (USA), Inc.); 1,3-Dioxolane derivs. as cholesterol lowering agents. JP 1992308588; US 5158949 . |
| 【3】 Walker, K.A.M.; Rotstein, D.M.; Kertesz, D.J.; et al.; Selective inhibition of mammalian lanosterol 14alpha-demethylase: A possible strategy for cholesterol lowering. J Med Chem 1993, 36, 15, 2235-7. |
| 【4】 Prous, J.; Mealy, N.; Castañer, J.; RS-21607-197. Drugs Fut 1994, 19, 2, 125. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 16481 | 1-(bromomethyl)-4-chlorobenzene | 622-95-7 | C7H6BrCl | 详情 | 详情 |
| (II) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (III) | 16483 | 1-(3-butenyl)-4-chlorobenzene | C10H11Cl | 详情 | 详情 | |
| (IV) | 16484 | 2-(4-chlorophenethyl)oxirane | C10H11ClO | 详情 | 详情 | |
| (V) | 10255 | Imidazole; 1H-Imidazole | 288-32-4 | C3H4N2 | 详情 | 详情 |
| (VI) | 16486 | 4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol | C13H15ClN2O | 详情 | 详情 | |
| (VII) | 16487 | 4-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanone | C13H13ClN2O | 详情 | 详情 | |
| (VIII) | 16488 | (2S)-2,3-dihydroxypropyl 4-methylbenzenesulfonate | C10H14O5S | 详情 | 详情 | |
| (IX) | 16489 | [(2S,4S)-2-(4-chlorophenethyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl 4-methylbenzenesulfonate | C23H25ClN2O5S | 详情 | 详情 | |
| (X) | 16490 | 4-aminophenylhydrosulfide; 4-aminothiophenol; 4-aminobenzenethiol | 1193-02-8 | C6H7NS | 详情 | 详情 |