|
【结 构 式】 
|
【分子编号】39886 【品名】diethyl (2-bromoethoxy)methylphosphonate 【CA登记号】 |
【 分 子 式 】C7H16BrO4P 【 分 子 量 】275.079402 【元素组成】C 30.56% H 5.86% Br 29.05% O 23.27% P 11.26% |
合成路线1
该中间体在本合成路线中的序号：(IV)PMEA was prepared by a straightforward route from readily available 2-acetoxyethoxymethyl chloride (I). The key intermediate, diethyl 2-bromoethylmethoxyphosphonate (IV), was coupled with adenine (V) in the presence of sodium hydride, followed by hydrolysis to afford PMEA.
| 【1】 Hwang, J.-T.; Choi, J.-R.; Novel phosphonate nucleosides as antiviral agents. Drugs Fut 2004, 29, 2, 163. |
| 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) | 63950 | 2-(chloromethoxy)ethyl acetate | C5H9ClO3 | 详情 | 详情 | |
| (II) | 39883 | 2-[(diethoxyphosphoryl)methoxy]ethyl acetate | C9H19O6P | 详情 | 详情 | |
| (III) | 39884 | diethyl (2-hydroxyethoxy)methylphosphonate | C7H17O5P | 详情 | 详情 | |
| (IV) | 39886 | diethyl (2-bromoethoxy)methylphosphonate | C7H16BrO4P | 详情 | 详情 | |
| (V) | 10343 | 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine | 73-24-5 | C5H5N5 | 详情 | 详情 |
| (VI) | 39673 | diethyl [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonate | C12H20N5O4P | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The 9-[2-(phosphonomethoxy)ethyl]adenine (VIII), intermediate in the synthesis of adefovir has been obtained as follows: 1) The partial hydrolysis of 2-acetoxyethoxymethylphosphonic acid diethyl ester (I) with Dowex 50XB in ethanol gives the corresponding 2-hydroxyethoxymethylphosphonate (II), which is treated with CCl4/PPh3, with CBr4/PPh3 or with TsCl yielding 2-choroethoxy (III), 2-bromoethoxy (IV) or 2-tosyloxyethoxy (V) derivatives, respectively (1). The condensation of (III), (IV) or (V) with adenine (VI) by means of NaH in hot DMF affords 9-[2-(diethoxyphosphorylmethoxy)ethyl]adenine (VII), which is finally treated with TMS-Br in acetonitrile to give the desired intermediate 9-[2-(phosphonomethoxy)ethyl]adenine (VIII). 2) The condensation of N6-benzoyl-9-(2-hydroxyethyl)adenine (IX) with tosyloxymethylphosphonic acid dimethyl ester (X) by means of NaH in warm DMF gives 9-[2-(dimethoxyphosphorylmethoxy)ethyl]adenine (X), which is treated first with NaOH in DMF/water and finally with TMS-I in DMF to afford the desired intermediate 9-[2-(phosphonomethoxy)ethyl]adenine (VIII).
| 【1】 Rosenberg, I.; Holý, A.; Synhtesis of 9-(2-phosphonylmethoxyethyl)adenine and related compounds. Coll Czech Chem Commun 1987, 52, 2801. |
| 【2】 Holý, A.; et al.; Synthesi of N-(2-phosphonylmethoxyethyl) derivatives of heterocyclic bases. Coll Czech Chem Commun 1989, 54, 2190. |
| 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) | 39883 | 2-[(diethoxyphosphoryl)methoxy]ethyl acetate | C9H19O6P | 详情 | 详情 | |
| (II) | 39884 | diethyl (2-hydroxyethoxy)methylphosphonate | C7H17O5P | 详情 | 详情 | |
| (III) | 39885 | diethyl (2-chloroethoxy)methylphosphonate | C7H16ClO4P | 详情 | 详情 | |
| (IV) | 39886 | diethyl (2-bromoethoxy)methylphosphonate | C7H16BrO4P | 详情 | 详情 | |
| (V) | 39887 | diethyl [2-[(4-methylphenyl)sulfonyl]ethoxy]methylphosphonate | C14H23O6PS | 详情 | 详情 | |
| (VI) | 10343 | 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine | 73-24-5 | C5H5N5 | 详情 | 详情 |
| (VII) | 39673 | diethyl [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonate | C12H20N5O4P | 详情 | 详情 | |
| (VIII) | 16165 | [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonic acid | C8H12N5O4P | 详情 | 详情 | |
| (IX) | 39888 | N-[9-(2-hydroxyethyl)-9H-purin-6-yl]benzamide | C14H13N5O2 | 详情 | 详情 | |
| (X) | 39889 | (dimethoxyphosphoryl)methyl 4-methylbenzenesulfonate | C10H15O6PS | 详情 | 详情 | |
| (XI) | 39890 | dimethyl [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonate | C10H16N5O4P | 详情 | 详情 |