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【结 构 式】 
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【分子编号】30270 【品名】bromo[(diethoxyphosphoryl)(difluoro)methyl]zinc 【CA登记号】 |
【 分 子 式 】C5H10BrF2O3PZn 【 分 子 量 】332.3971684 【元素组成】C 18.07% H 3.03% Br 24.04% F 11.43% O 14.44% P 9.32% Zn 19.67% |
合成路线1
该中间体在本合成路线中的序号：(II)Treatment of alkenyl iodide (I) with the organozinc reagent (II) in the presence of CuBr afforded the unsaturated alpha,alpha-difluorophosphonate (III), which was condensed with diazomethane to give the cyclopropane derivative (IV). Acid hydrolysis of the tetrahydropyranyl ether of (IV) provided alcohol (V), which was converted into tosylate (VI) with p-TsCl and Et3N. Coupling of (VI) with 6-chloropurine (VII) gave the 9-alkylated purine (VIII). Finally, hydrolysis of both phosphonate esters and the chloro atom of purine (VIII) was carried out upon treatment with bromotrimethylsilane, followed by aqueous hydrolysis to yield the title compound.
| 【1】 Yokomatsu, T.; Abe, H.; Sato, M.; Suemune, K.; Kihara, T.; Soeda, S.; Shimeno, H.; Shibuya, S.; Synthesis of 1,1-difluoro-5-(1H-9-purinyl)-2-pentenylphosphonic acids and the related methano analogues. Remarkable effect of the nucleobases and the cyclopropane rings on inhibitory activity toward purine nucleoside phosphorylase. Bioorg Med Chem 1998, 6, 12, 2495. |
| 【2】 Shimeno, H.; Suemune, K.; Abe, H.; Yokomatsu, T.; Kihara, T.; Sato, M.; Soeda, S.; Shibuya, S.; Synthesis of novel nucleotide analogues possessing difluoromethylene phosphonate pharmacophore. Evaluation of the inhibitory activities of PNPases. Symp Med Chem 1998, Abst 1-P-06. |
| 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) | 30269 | (E)-4-iodo-3-butenyl tetrahydro-2H-pyran-2-yl ether; 2-[[(E)-4-iodo-3-butenyl]oxy]tetrahydro-2H-pyran | C9H15IO2 | 详情 | 详情 | |
| (II) | 30270 | bromo[(diethoxyphosphoryl)(difluoro)methyl]zinc | C5H10BrF2O3PZn | 详情 | 详情 | |
| (III) | 30271 | diethyl (E)-1,1-difluoro-5-(tetrahydro-2H-pyran-2-yloxy)-2-pentenylphosphonate | C14H25F2O5P | 详情 | 详情 | |
| (IV) | 30272 | diethyl difluoro[(1R,2S)-2-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]cyclopropyl]methylphosphonate | C15H27F2O5P | 详情 | 详情 | |
| (V) | 30273 | diethyl difluoro[(1R,2S)-2-(2-hydroxyethyl)cyclopropyl]methylphosphonate | C10H19F2O4P | 详情 | 详情 | |
| (VI) | 30274 | 2-[(1S,2R)-2-[(diethoxyphosphoryl)(difluoro)methyl]cyclopropyl]ethyl 4-methylbenzenesulfonate | C17H25F2O6PS | 详情 | 详情 | |
| (VII) | 17692 | 6-Chloropurine; 6-chloro-9H-purine | 87-42-3 | C5H3ClN4 | 详情 | 详情 |
| (VIII) | 30275 | diethyl [(1R,2S)-2-[2-(6-chloro-9H-purin-9-yl)ethyl]cyclopropyl](difluoro)methylphosphonate | C15H20ClF2N4O3P | 详情 | 详情 |