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【结 构 式】 
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【分子编号】12210 【品名】(2R,3R,4R,5R)-4-bromo-2-(hydroxymethyl)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-3-furanyl acetate 【CA登记号】 |
【 分 子 式 】C12H15BrN2O6 【 分 子 量 】363.16498 【元素组成】C 39.69% H 4.16% Br 22% N 7.71% O 26.43% |
合成路线1
该中间体在本合成路线中的序号：(XV)4) Reaction of thymine (IX) with 1-O-acetyl-2,3,5-tri-O-benzoylribose (X) and hexamethyldisilazane, trimethylsilyl chloride and trifluoromethanesulfonic acid in acetonitrile, followed by cleavage of the protecting groups with sodium methoxide in methanol gives 5-methyluridine (XI). Compound (XI) is converted to (XII) by means of 2-acetoxyisobutyryl bromide in acetonitrile, subsequent reaction of (XII) with zinc-copper in dimethylformamide yields (XIII), which is finally deprotected with sodium methoxide in methanol. 5) 5-Methyluridine (XI) can also be converted to (XIV) by means of trimethylorthoacetate in acetic acid. Compound (XIV) is then treated with hydrobromic acid to give (XV), which is treated with zinc in acetonitrile and EDTA or is successively treated with acetic anhydride, zirconium oxide and tributylamine.
| 【1】 Ineyama, T.; Shiragami, H.; Izawa, K.; Uchida, Y.; Synthesis of 1-(2,3-dideoxy-beta-d-glycero-pent-2-enofuranosyl)thymine (d4T; stavudine) from 5-methyluridine. Nucleosides Nucleotides 1996, 15, 1-3, 47. |
| 【2】 Ebata, T.; Matsushita, H.; Mizutani, N.; Itoh, K. (Japan Tobacco Inc.); Process for producing 2',3'-dideoxy-2',3'-didehydronucleoside. WO 9202516 . |
| 【3】 Shiragami, H.; Uchida, Y.; Izawa, K. (Ajinomoto Co., Inc.); Nucleoside derivs. and production thereof. EP 0519464 . |
| 【4】 Tortolani, D.R.; Brodfuehrer, P.R.; Starrett, J.E. Jr.; Martin, J.C.; Howell, H.G.; Mansuri, M.M.; Wos, J.A.; Preparation of 1-(2,3-ideoxy-beta-d-glycero-pent-2-enofuranosyl)thymine (d4T) and 2',30-dideoxyadenosine (ddA): General methods for the synthesis of 2',3'-olefinic and 2',3'-dideoxy nucleoside analogues active against HIV. J Org Chem 1989, 54, 4780-5. |
| 【5】 Robinson, C.; Castaner, J.; Stavudine. Drugs Fut 1994, 19, 10, 925. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 12204 | 5-Methyl-2,4(1H,3H)-pyrimidinedione; Thymine | 65-71-4 | C5H6N2O2 | 详情 | 详情 |
| (X) | 12205 | (2R,3R,4S,5R)-3,4-bis(benzyloxy)-5-[(benzyloxy)methyl]tetrahydro-2-furanyl acetate | C28H30O6 | 详情 | 详情 | |
| (XI) | 12206 | 1-[(2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-5-methyl-2,4(1H,3H)-pyrimidinedione; 5-Methyluridine | 1463-10-1 | C10H14N2O6 | 详情 | 详情 |
| (XII) | 12207 | [(2R,3R,4R,5R)-3-(acetoxy)-4-bromo-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl]methyl 2-(acetoxy)-2-methylpropanoate | C18H23BrN2O9 | 详情 | 详情 | |
| (XIII) | 12208 | [(2S,5R)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]-2,5-dihydro-2-furanyl]methyl 2-(acetoxy)-2-methylpropanoate | C16H20N2O7 | 详情 | 详情 | |
| (XIV) | 12209 | 1-[(3aR,4R,6R,6aR)-6-(Hydroxymethyl)-2-methoxy-2-methyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]-5-methyl-2,4(1H,3H)-pyrimidinedione | C13H18N2O7 | 详情 | 详情 | |
| (XV) | 12210 | (2R,3R,4R,5R)-4-bromo-2-(hydroxymethyl)-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-3-furanyl acetate | C12H15BrN2O6 | 详情 | 详情 |