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【结 构 式】 
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【分子编号】25279 【品名】1-[(2R,4R,5S)-4,5-bis(hydroxymethyl)tetrahydro-2-thiophenyl]-5-iodo-2,4(1H,3H)-pyrimidinedione 【CA登记号】 |
【 分 子 式 】C10H13IN2O4S 【 分 子 量 】384.19477 【元素组成】C 31.26% H 3.41% I 33.03% N 7.29% O 16.66% S 8.35% |
合成路线1
该中间体在本合成路线中的序号：(XVI)Acetate (XI) was coupled with the bis-silylated uracil (XII) in the presence of trimethylsilyl triflate to give the 1:1 mixture of glycosylated products (XIII). The benzyl protecting groups of (XIII) were removed with BCl3, and the resulting mixture of diols was separated by preparative RP-HPLC. The desired isomer (XIV) was acetylated with Ac2O to give the diacetate ester (XV). After iodination of (XV) using LiI and ammonium cerium nitrate, the acetate groups were removed by treatment with methanolic NaOMe to afford 5-iodouracil (XVI). Subsequent Heck reaction of (XVI) with methyl acrylate (XVII) in the presence of Pd(OAc)2 and PPh3 produced ester (XVIII) together with some deiodinated product. Hydrolysis of the ester function of (XVIII) gave carboxylic acid (XIX), which was finally treated with N-bromosuccinimide and K2CO3 in DMF to yield the target bromovinyl compound.
| 【1】 Upcroft, P.; Campbell, R.W.; Benakli, K.; Upcroft, J.A.; Vanelle, P.; Efficacy of new 5-nitroimidazoles against metronidazole-susceptible and -resistant Giardia, Trichomonas, and Entamoeba spp. Antimicrob Agents Chemother 1999, 43, 1, 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 |
|---|---|---|---|---|---|---|
| (XI) | 25274 | (4R,5S)-4,5-bis[(benzyloxy)methyl]tetrahydro-2-thiophenyl acetate | C22H26O4S | 详情 | 详情 | |
| (XII) | 25275 | 1,3-bis(trimethylsilyl)-2,4(1H,3H)-pyrimidinedione | C10H20N2O2Si2 | 详情 | 详情 | |
| (XIII) | 25276 | 1-[(4R,5S)-4,5-bis[(benzyloxy)methyl]tetrahydro-2-thiophenyl]-2,4(1H,3H)-pyrimidinedione | C24H26N2O4S | 详情 | 详情 | |
| (XIV) | 25277 | 1-[(2R,4R,5S)-4,5-bis(hydroxymethyl)tetrahydro-2-thiophenyl]-2,4(1H,3H)-pyrimidinedione | C10H14N2O4S | 详情 | 详情 | |
| (XV) | 25278 | [(2S,3R,5R)-2-[(acetoxy)methyl]-5-[2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-3-thiophenyl]methyl acetate | C14H18N2O6S | 详情 | 详情 | |
| (XVI) | 25279 | 1-[(2R,4R,5S)-4,5-bis(hydroxymethyl)tetrahydro-2-thiophenyl]-5-iodo-2,4(1H,3H)-pyrimidinedione | C10H13IN2O4S | 详情 | 详情 | |
| (XVII) | 10164 | ethyl acrylate | 140-88-5 | C5H8O2 | 详情 | 详情 |
| (XVIII) | 25280 | methyl (E)-3-[1-[(2R,4R,5S)-4,5-bis(hydroxymethyl)tetrahydro-2-thiophenyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-2-propenoate | C14H18N2O6S | 详情 | 详情 | |
| (XIX) | 25281 | (E)-3-[1-[(2R,4R,5S)-4,5-bis(hydroxymethyl)tetrahydro-2-thiophenyl]-2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinyl]-2-propenoic acid | C13H16N2O6S | 详情 | 详情 |