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【结 构 式】 
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【药物名称】Atofluding, A-OT 【化学名称】1-Acetyl-5-fluoro-3-(2-methylphenyl)uracil 【CA登记号】71861-76-2 【 分 子 式 】C14H11FN2O4 【 分 子 量 】290.25317 |
【开发单位】Xian Lijun Pharmaceutical (Originator), Taiho (Not Determined) 【药理作用】Chemical Delivery Systems, DRUG DELIVERY, Drug Delivery Systems, ONCOLYTIC DRUGS, Antimetabolites |
合成路线1
Atofluding can be prepared by several similar ways: a) Acylation of 5-fluorouracil (I) with acetic anhydride in refluxing pyridine gives 1-acetyl-5-fluorouracil (II), which is then acylated with 2-methylbenzoyl chloride (V) by means of either TEA in dioxane at room temperature or pyridine in dioxane at 80 C. b) Acylation of 5-fluorouracil (I) with 2-methylbenzoyl chloride (V) in pyridine at room temperature yields 5-fluoro-3-(2-methylbenzoyl)uracil (III), which is then acylated with acetic anhydride at 80 C or with acetic anhydride by means of TEA in cooled dioxane. c) Acylation of 5-fluorouracil (I) with acetyl chloride by means of TEA in dioxane at room temperature provides 1,3-diacetyl-5-fluorouracil (IV), which is then acytated with 2-methylbenzoyl chloride (V) by means of TEA in dioxane.
| 【1】 Kametani, T.; Hiiragi, M.; Kigasawa, K.; et al.; Studies on the synthesis of chemotherapeutics. 10. Synthesis and antitumor activity of N-acyl- and N-(alkoxycarbonyl)-5-fluorouracil derivatives. J Med Chem 1980, 23, 12, 1324. |
| 【2】 Castaner, J.; Zhang, Z.; Xu, W.; Atofluding. Drugs Fut 2001, 26, 10, 935. |
| 【3】 Okada, T.; Uracil derivs., process for preparing the same, and oncotic preparation thereof. JP 1979135782; WO 7900922 . |
| 【4】 Palleja Martinez, J.; Okada, T.; Process to obtain new 5-fluorouracil derivs., specifically N1-acyl-substd.-N3-ortho-toluyl-5-fluorouracils. ES 2015772 . |
| 【5】 Hoffer, M. (Hoffmann-La Roche, Inc.); Preparation of thymidine and deoxyfluorouridine, and intermediates therefor. US 2949451 . |
| 【6】 Okada, T.; Palleja Martinez, J.; Process to obtain a new 5-fluorouracil deriv.. ES 2015151 . |
| 【7】 Hoffer, M. (Hoffmann-La Roche, Inc.); Mercury salts of nitrogen heterocyclics and preparation thereof. US 3041335 . |
| 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) | 29241 | 5-fluoro-2,4(1H,3H)-pyrimidinedione；5-fluorouracil；5-Fluoro-2,4-pyrimidinedione;5-Fluoropyrimidine-2,4-dione | 51-21-8 | C4H3FN2O2 | 详情 | 详情 |
| (II) | 48658 | 1-acetyl-5-methyl-2,4(1H,3H)-pyrimidinedione | C7H8N2O3 | 详情 | 详情 | |
| (III) | 48659 | 5-fluoro-3-(2-methylbenzoyl)-2,4(1H,3H)-pyrimidinedione | C12H9FN2O3 | 详情 | 详情 | |
| (IV) | 48660 | 1,3-diacetyl-5-fluoro-2,4(1H,3H)-pyrimidinedione | C8H7FN2O4 | 详情 | 详情 | |
| (V) | 14770 | 2-methylbenzoyl chloride; o-Toluoyl chloride | 933-88-0 | C8H7ClO | 详情 | 详情 |