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【结 构 式】 
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【药物名称】Eniluracil, GW-776, 5-EU, 776C85 【化学名称】5-Ethynyluracil 【CA登记号】59989-18-3 【 分 子 式 】C6H4N2O2 【 分 子 量 】136.11098 |
【开发单位】GlaxoSmithKline (Originator) 【药理作用】Breast Cancer Therapy, Colorectal Cancer Therapy, Inhibitors of the Degradation of Anticancer Drugs, Modulators of the Therapeutic Activity of Antineoplastic Agents, ONCOLYTIC DRUGS, Pancreatic Cancer Therapy |
合成路线1
This compound has been obtained by two similar ways: 1. The reaction of 5-iodouracil (I) with trimethylsilylacetylene (II) by means of PdCl2(PPh3)2 and CuI2 in TEA/DMF gives 5-(trimethylsilylethynyl)uracil (III), which is then desilylated with sodium methoxide or NaOH in methanol. 2. The reaction of 5-iodouracil (I) with POCl3 at 120 C catalyzed by N,N-diethylaniline gives 2,4-dichloro-5-iodopyrimidine (IV), which by reaction with NaOMe in methanol is converted into 2,4-dimethoxy-5-iodopyrimidine (V). The condensation of (V) with trimethylsilylacetylene by means of PdCl2(PPh3)2 and CuI2 in TEA/DMF yields 2,4-dimethoxy-5-(trimethylsilylethynyl)pyrimidine (VI), which is treated with NaI and Tms-Cl in refluxing acetonitrile to afford 5-(trimethylsilylethynyl)uracil (III).
| 【1】 Cooke, J.W.B.; et al.; Process research and development of a dihydropyrimidine dehydrogenase inactivator: Large-scale preparation of eniluracil using a Sonogashira coupling. Org Process Res Dev 2001, 5, 4, 383. |
| 【2】 Spector, T.; Porter, D.J.T.; Rahim, S.G. (Glaxo Wellcome plc); Uracil reductase inactivators. EP 0550580; JP 1994504263; JP 1998045623; WO 9204901 . |
| 【3】 Spector, T.; Porter, D.J.T.; Rahim, S.G. (Glaxo Wellcome plc); Enzyme inactivators. EP 0539442; EP 0711555; JP 1994502619; JP 2000297076; WO 9201452 . |
| 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) | 11867 | 5-Iodo-2,4(1H,3H)-pyrimidinedione | 696-07-1 | C4H3IN2O2 | 详情 | 详情 |
| (II) | 23897 | ethynyl(trimethyl)silane；trimethylsilyl acetylene | 1066-54-2 | C5H10Si | 详情 | 详情 |
| (III) | 47911 | 5-[2-(trimethylsilyl)ethynyl]-2,4(1H,3H)-pyrimidinedione | C9H12N2O2Si | 详情 | 详情 | |
| (IV) | 11868 | 2,4-Dichloro-5-iodopyrimidine | C4HCl2IN2 | 详情 | 详情 | |
| (V) | 11869 | 5-Iodo-2-methoxy-4-pyrimidinyl methyl ether; 5-Iodo-2,4-dimethoxypyrimidine | 52522-99-3 | C6H7IN2O2 | 详情 | 详情 |
| (VI) | 47912 | 2,4-dimethoxy-5-[2-(trimethylsilyl)ethynyl]pyrimidine; 2-methoxy-5-[2-(trimethylsilyl)ethynyl]-4-pyrimidinyl methyl ether | C11H16N2O2Si | 详情 | 详情 |