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【结 构 式】 
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【分子编号】64233 【品名】4-(9-{[(2,2,2-trifluoroethyl)amino]carbonyl}-9H-fluoren-9-yl)butylphosphonic acid 【CA登记号】 |
【 分 子 式 】C20H21F3NO4P 【 分 子 量 】427.3600516 【元素组成】C 56.21% H 4.95% F 13.34% N 3.28% O 14.98% P 7.25% |
合成路线1
该中间体在本合成路线中的序号：(VII)Alkylation of the dilithio derivative of fluorene-9-carboxylic acid (I) with diethyl 4-bromobutylphosphonate (II) affords adduct (III). After conversion of acid (III) to the corresponding acid chloride (IV), condensation with 2,2,2-trifluoroethylamine (V) affords amide (VI). The phosphonate ethyl ester (VI) is cleaved by means of bromotrimethylsilane yielding phosphonic acid (VII), which is further activated as the phosphonic acid chloride (VIII) by using oxalyl chloride in the presence of DMF. Finally, condensation of acid chloride (VIII) with (6-methylpyridin-2-yl)methanol (IX) leads to the target bis-pyridinylmethyl ester.
| 【1】 Magnin, D.R.; Biller, S.A.; Wetterau, J.; Robl, J.A.; Dickson, J.K. Jr.; Prakash, T.; Harrity, T.W.; Lawrence, R.M.; Sun, C.-Q.; Wang, T.; Logan, J.; Fryszman, O.; Connolly, F.; Jolibois, K.; Kunselman, L.; Microsomal triglyceride transfer protein inhibitors: Discovery and synthesis of alkyl phosphonates as potent MTP inhibitors and cholesterol lowering agents. Bioorg Med Chem Lett 2003, 13, 7, 1337. |
| 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) | 47744 | 9H-fluorene-9-carboxylic acid; 9-Fluorenecarboxylic acid; Diphenyleneacetic acid; Fluorene-9-carboxylic acid | 1989-33-9 | C14H10O2 | 详情 | 详情 |
| (II) | 64229 | diethyl 4-bromobutylphosphonate | C8H18BrO3P | 详情 | 详情 | |
| (III) | 64230 | 9-[4-(diethoxyphosphoryl)butyl]-9H-fluorene-9-carboxylic acid | C22H27O5P | 详情 | 详情 | |
| (IV) | 64231 | diethyl 4-[9-(chlorocarbonyl)-9H-fluoren-9-yl]butylphosphonate | C22H26ClO4P | 详情 | 详情 | |
| (V) | 42542 | 2,2,2-trifluoroethylamine; 2,2,2-trifluoro-1-ethanamine | 753-90-2 | C2H4F3N | 详情 | 详情 |
| (VI) | 64232 | diethyl 4-(9-{[(2,2,2-trifluoroethyl)amino]carbonyl}-9H-fluoren-9-yl)butylphosphonate | C24H29F3NO4P | 详情 | 详情 | |
| (VII) | 64233 | 4-(9-{[(2,2,2-trifluoroethyl)amino]carbonyl}-9H-fluoren-9-yl)butylphosphonic acid | C20H21F3NO4P | 详情 | 详情 | |
| (VIII) | 64234 | 4-(9-{[(2,2,2-trifluoroethyl)amino]carbonyl}-9H-fluoren-9-yl)butylphosphonic dichloride | C20H19Cl2F3NO2P | 详情 | 详情 | |
| (IX) | 64235 | (6-methyl-2-pyridinyl)methanol | C7H9NO | 详情 | 详情 |