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【结 构 式】 
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【分子编号】11792 【品名】methyl (E)-7-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-5-hydroxy-3-oxo-6-heptenoate 【CA登记号】 |
【 分 子 式 】C25H26FNO4 【 分 子 量 】423.4841832 【元素组成】C 70.91% H 6.19% F 4.49% N 3.31% O 15.11% |
合成路线1
该中间体在本合成路线中的序号：(VII)The condensation of 4-fluorophenacyl chloride (I) with N-isopropylaniline gives N-(4-fluorobenzoylmethyl)-N-isopropylaniline (II), which is cyclized in a conventional way to 3-(4-fluorophenyl)-1-isopropyl-indole (III) and condensed with 3-(dimethylamino)acrolein (IV) by means of POCl3 in refluxing acetonitrile, yielding 3-[3-(4-fluorophenyl)-1-isopropyl-indol-2-yl]acrolein (V). The condensation of (V) with methylacetoacetate (VI) by means of NaH and butyl-lithium in THF affords methyl 7-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-5-hydroxy-3-oxo-6-heptenoate (VII), which is reduced with triethylborane and NaBH4 in THF, giving the dihydroxy ester (VIII). Finally, this compound is hydrolyzed with NaOH in ethanol.
| 【1】 Kathawala, F. (Novartis AG); Analogs of mevalolactone and derivs. thereof, processes for their production, pharmaceutical compsns. containing them and their use as pharmaceuticals. JP 1991047167; US 4739073; WO 8402131 . |
| 【2】 Kapa, P.K. (Novartis AG); 6-Substituted-4-hydroxy-tetrahydropyran-2-ones. US 4571428 . |
| 【3】 Chen, K.-M.; Hardtmann, G.E.; Lee, G.T.; Linder, J.; Wattanasin, S. (Novartis AG; Novartis Deutschland GmbH); Preparation of olefinic cpds. EP 0244364 . |
| 【4】 Castaner, J.; Prous, J.; Fluvastatin Sodium. Drugs Fut 1991, 16, 9, 804. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 27905 | N-isopropyl-N-phenylamine | 768-52-5 | C9H13N | 详情 | 详情 | |
| (I) | 11786 | 2-Chloro-1-(4-fluorophenyl)-1-ethanone; 2-Chloro-4'-fluoroacetophenone | 456-04-2 | C8H6ClFO | 详情 | 详情 |
| (II) | 11787 | 1-(4-Fluorophenyl)-2-(isopropylanilino)-1-ethanone | C17H18FNO | 详情 | 详情 | |
| (III) | 11788 | 3-(4-Fluorophenyl)-1-isopropyl-1H-indole | 93957-49-4 | C17H16FN | 详情 | 详情 |
| (IV) | 11789 | (E)-3-(Dimethylamino)-2-propenal | 692-32-0 | C5H9NO | 详情 | 详情 |
| (V) | 11790 | (E)-3-[3-(4-Fluorophenyl)-1-isopropyl-1H-indol-2-yl]-2-propenal | C20H18FNO | 详情 | 详情 | |
| (VI) | 11791 | methyl 3-oxobutanoate; Methyl acetoacetate | 105-45-3 | C5H8O3 | 详情 | 详情 |
| (VII) | 11792 | methyl (E)-7-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-5-hydroxy-3-oxo-6-heptenoate | C25H26FNO4 | 详情 | 详情 | |
| (VIII) | 11793 | methyl (3R,5S,6E)-7-[3-(4-fluorophenyl)-1-isopropyl-1H-indol-2-yl]-3,5-dihydroxy-6-heptenoate | C25H28FNO4 | 详情 | 详情 |