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【结 构 式】 
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【药物名称】LB-80317 【化学名称】1-(2-Amino-6-hydroxy-9H-purin-9-ylmethyl)cyclopropyloxymethylphosphonic acid 【CA登记号】441785-24-6 【 分 子 式 】C10H14N5O5P 【 分 子 量 】315.22738 |
【开发单位】LG Chem (Originator) 【药理作用】Anti-Hepatitis B Virus Drugs, Anti-Hepatitis Virus Drugs, ANTIINFECTIVE THERAPY, Antiviral Drugs |
合成路线1
The key intermediate, cyclopropanol (I), was prepared by titanium-mediated Kulinkovich cyclopropanation in over 80% yield as a white solid. Etherification of compound (I) with diisopropyl bromomethylphosphonate, followed by sequential desilylation, mesylation and coupling reaction with 6-chloroguanine (VII), gave compound (VIII). Finally, hydrolysis of compound (VIII) in the presence of TMSBr afforded LB-80317.
| 【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) | 60566 | ethyl 2-{[tert-butyl(diphenyl)silyl]oxy}acetate | C20H26O3Si | 详情 | 详情 | |
| (II) | 60567 | 1-({[tert-butyl(diphenyl)silyl]oxy}methyl)cyclopropanol | C20H26O2Si | 详情 | 详情 | |
| (III) | 60568 | diisopropyl bromomethylphosphonate | C7H16BrO3P | 详情 | 详情 | |
| (IV) | 60569 | diisopropyl {[1-({[tert-butyl(diphenyl)silyl]oxy}methyl)cyclopropyl]oxy}methylphosphonate | C27H41O5PSi | 详情 | 详情 | |
| (V) | 60570 | diisopropyl {[1-(hydroxymethyl)cyclopropyl]oxy}methylphosphonate | C11H23O5P | 详情 | 详情 | |
| (VI) | 63954 | diisopropyl {[1-({[methyl(dimethylene)-lambda~6~-sulfanyl]oxy}methyl)cyclopropyl]oxy}methylphosphonate | C14H29O5PS | 详情 | 详情 | |
| (VII) | 63955 | 6,9-dichloro-9H-purin-2-ylamine; 6,9-dichloro-9H-purin-2-amine | C5H3Cl2N5 | 详情 | 详情 | |
| (VIII) | 63956 | diisopropyl ({1-[(2-amino-6-chloro-9H-purin-9-yl)methyl]cyclopropyl}oxy)methylphosphonate | C16H25ClN5O4P | 详情 | 详情 |