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【结 构 式】 
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【分子编号】16164 【品名】diisopropyl [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonate 【CA登记号】 |
【 分 子 式 】C14H24N5O4P 【 分 子 量 】357.349622 【元素组成】C 47.06% H 6.77% N 19.6% O 17.91% P 8.67% |
合成路线1
该中间体在本合成路线中的序号：(III)Adefovir dipivoxil can be obtained by two similar ways: 1) The reaction of adenine (I) with 2-(diisopropoxyphosphorylmethoxy)ethyl methanesulfonate (II) by means of cesium carbonate in DMF gives the expected condensation product (III), which is converted into the phosphonic acid (IV) by treatment with trimethylsilyl bromide in acetonitrile (1). Finally, this compound is condensed with chloromethyl pivalate (V) by means of N,N'-dicyclohexylmorpholine-4-carboxamidine in DMF. 2) The final condensation of the phosphonic acid (IV) can also be performed with iodomethyl pivalate (VI) in pyridine.
| 【1】 Benzaria, S.; Pélicano, H.; Johnson, R.; Maury, G.; Imbach, J.-L.; Aubertin, A.-M.; Obert, G.; Gosselin, G.; Synthesis, in vitro antiviral evaluation, and stability studies of bis(S-acyl-2-thioethyl) ester derivatives of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) as potential PMEA prodrugs with improved oral bioavailability. J Med Chem 1996, 39, 25, 4958-65. |
| 【2】 Prous, J.; Graul, A.; Castaner, J.; Adefovir Dipivoxil. Drugs Fut 1997, 22, 8, 825. |
| 【3】 Starrett, J.E. Jr.; Mansuri, M.M.; Martin, J.C.; Tortolani, D.R.; Bronson, J.J. (Bristol-Myers Squibb Co.); Prodrug of phosphonates. EP 0481214; JP 1992230694 . |
| 【4】 Starrett, J.E. Jr.; Tortolani, D.R.; Russell, J.; Hitchcock, M.J.M.; Whiterock, V.; Martin, J.C.; Mansuri, M.M.; Synthesis, oral bioavailability determination, and in vitro evaluation of prodrugs of the antiviral agent 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). J Med Chem 1994, 37, 12, 1857-64. |
| 【5】 Starrett, J.E. Jr.; et al.; Synthesis and in vitro evaluation of a phosphonate prodrug: bis(pivaloyloxymethyl) 9-(2-phosphonylmethoxyethyl)adenine. Antivir Res 1992, 19, 3, 267-73. |
| 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) | 10343 | 9H-Purin-6-amine; 9H-Purin-6-ylamine; Adenine | 73-24-5 | C5H5N5 | 详情 | 详情 |
| (II) | 16163 | 2-[(diisopropoxyphosphoryl)methoxy]ethyl methanesulfonate | C10H23O7PS | 详情 | 详情 | |
| (III) | 16164 | diisopropyl [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonate | C14H24N5O4P | 详情 | 详情 | |
| (IV) | 16165 | [2-(6-amino-9H-purin-9-yl)ethoxy]methylphosphonic acid | C8H12N5O4P | 详情 | 详情 | |
| (V) | 16166 | chloromethyl pivalate | 18997-19-8 | C6H11ClO2 | 详情 | 详情 |
| (VI) | 11159 | iodomethyl pivalate | C6H11IO2 | 详情 | 详情 |