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【结 构 式】 
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【分子编号】22396 【品名】(2R,3R,4S,5R)-2-(6-amino-2-iodo-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol 【CA登记号】35109-88-7 |
【 分 子 式 】C10H12IN5O4 【 分 子 量 】393.14105 【元素组成】C 30.55% H 3.08% I 32.28% N 17.81% O 16.28% |
合成路线1
该中间体在本合成路线中的序号：(I)2-Iodoadenosine (I) was protected as the ketal (II) on treatment with p-toluenesulfonic in an excess of acetone. This compound was oxidized to the acid (III) with potassium permanganate in aqueous alkaline solution. Deprotection of the ketal was accomplished on heating in 50% formic acid to give IV, which was then esterified in ethanolic solution by means of dropwise addition of thionyl chloride. The resulting ethyl ester (V) was dissolved in liquid ethylamine to afford amide (VI). Finally, VI was coupled with 1-phenyl-2-propyn-1-ol (VII) in the presence of triethylamine and a trace of bis(triphenylphosphine)palladium dichloride and cuprous iodide, to yield the title compound.
| 【1】 Dionisotti, S.; Ongini, E.; Camaioni, E.; Volpini, R.; Zocchi, C.; Conti, A.; Vittori, S.; Monopoli, A.; Cristalli, G.; 2-Alkynyl derivatives of adenosine-5'-N-ethylurona. J Med Chem 1994, 37, 11, 1720. |
| 【2】 Cristalli, G. (Schering Corp.); Adenosine derivs. having A2 agonist activity. US 5593975; WO 9322328 . |
| 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) | 22396 | (2R,3R,4S,5R)-2-(6-amino-2-iodo-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | 35109-88-7 | C10H12IN5O4 | 详情 | 详情 |
| (II) | 22397 | [(3aR,4R,6R,6aR)-6-(6-amino-2-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol | C13H16IN5O4 | 详情 | 详情 | |
| (III) | 22398 | (3aR,4S,6R,6aR)-6-(6-amino-2-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid | C13H14IN5O5 | 详情 | 详情 | |
| (IV) | 22399 | (2S,3S,4R,5R)-5-(6-amino-2-iodo-9H-purin-9-yl)-3,4-dihydroxytetrahydro-2-furancarboxylic acid | C10H10IN5O5 | 详情 | 详情 | |
| (V) | 22400 | ethyl (2S,3S,4R,5R)-5-(6-amino-2-iodo-9H-purin-9-yl)-3,4-dihydroxytetrahydro-2-furancarboxylate | C12H14IN5O5 | 详情 | 详情 | |
| (VI) | 22401 | (2S,3S,4R,5R)-5-(6-amino-2-iodo-9H-purin-9-yl)-N-ethyl-3,4-dihydroxytetrahydro-2-furancarboxamide | C12H15IN6O4 | 详情 | 详情 | |
| (VII) | 22402 | 1-phenyl-2-propyn-1-ol | 4187-87-5 | C9H8O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)The intermediate iodopurine (IX) was prepared as follows. Acetylation of guanosine (I) afforded the triacetate ester (II). Subsequent chlorination of (II) to the 6-chloropurine (III) was accomplished by treatment with phosphoryl chloride and N,N-dimethylaniline. Diazotization of (III) with isoamyl nitrite in the presence of CuI furnished the 6-chloro-2-iodopurine (IV). Displacement of the 6-chloro group of (IV) in liquid ammonia with concomitant ammonolysis of the acetate esters gave rise to the 6-amino derivative (V). The dioxolane ketal (VI) was then formed by treatment of (V) with 2,2-dimethoxypropane in the presence of p-toluenesulfonic acid. After oxidation of the primary alcohol of (VI) with alkaline KMnO4 to give (VII), its ketal hydrolysis using 50% formic acid produced the carboxylic acid (VIII). The required N-ethyl amide (IX) was then obtained by esterification with SOCl2/EtOH, followed by treatment with liquid ethylamine.
| 【1】 Linden, J.M.; MacDonald, T.; Glover, D.K.; Beller, G.A. (University of Virginia); Induction of pharmacological stress with adenosine receptor agonists. JP 2003502433; WO 0078774 . |
| 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) | 38958 | Guanosine; 2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydro-2-furanyl]-1,9-dihydro-6H-purin-6-one | 118-00-3 | C10H13N5O5 | 详情 | 详情 |
| (II) | 38959 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H19N5O8 | 详情 | 详情 | |
| (III) | 22299 | (2R,3R,4R,5R)-4-(acetoxy)-2-[(acetoxy)methyl]-5-(2-amino-6-chloro-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H18ClN5O7 | 详情 | 详情 | |
| (IV) | 59471 | (2R,3R,4R,5R)-4-(acetyloxy)-2-[(acetyloxy)methyl]-5-(6-chloro-2-iodo-9H-purin-9-yl)tetrahydro-3-furanyl acetate | C16H16ClIN4O7 | 详情 | 详情 | |
| (V) | 22396 | (2R,3R,4S,5R)-2-(6-amino-2-iodo-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydro-3,4-furandiol | 35109-88-7 | C10H12IN5O4 | 详情 | 详情 |
| (VI) | 22397 | [(3aR,4R,6R,6aR)-6-(6-amino-2-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methanol | C13H16IN5O4 | 详情 | 详情 | |
| (VII) | 22398 | (3aR,4S,6R,6aR)-6-(6-amino-2-iodo-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid | C13H14IN5O5 | 详情 | 详情 | |
| (VIII) | 22399 | (2S,3S,4R,5R)-5-(6-amino-2-iodo-9H-purin-9-yl)-3,4-dihydroxytetrahydro-2-furancarboxylic acid | C10H10IN5O5 | 详情 | 详情 | |
| (IX) | 22401 | (2S,3S,4R,5R)-5-(6-amino-2-iodo-9H-purin-9-yl)-N-ethyl-3,4-dihydroxytetrahydro-2-furancarboxamide | C12H15IN6O4 | 详情 | 详情 |