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【结 构 式】 
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【分子编号】14403 【品名】((1S,2R,3R)-3-amino-2-[[(cyclohexylcarbonyl)oxy]methyl]cyclobutyl)methyl cyclohexanecarboxylate 【CA登记号】 |
【 分 子 式 】C20H33NO4 【 分 子 量 】351.48636 【元素组成】C 68.34% H 9.46% N 3.99% O 18.21% |
合成路线1
该中间体在本合成路线中的序号：(XXXII)4) The reaction of the previously described chiral cyclobutanone (IX) with hydroxylamine gives the corresponding oxime (XXXI), which is reduced with H2 over PtO2 yielding [1R-(1alpha,2beta,3alpha)]-2,3-di(cyclohexylcarbonyloxymethyl) cyclobutane-1-amine (XXXII). The condensation of (XXXII) with 4,6-dichloropyrimidine-2-amine (XXXIII) affords (XXXIV), which is further condensed with 4-chlorophenyldiazonium chloride (XXXV) to give the 5-azo-pyrimidine derivative (XXXVI). The hydrogenation of the azo group of (XXXVI) with Zn/HCl yields the 2,5-diaminopyrimidine derivative (XXXVII), which is cyclized with triethyl orthoformate to afford [1R-(1alpha,2beta,3alpha)]-2-amino-9-[2,3-bis (cyclohexylcarbonyloxymethyl)cyclobutyl]-6-chloropurine (XXXVIII). Finally, this compound is converted into the final product in the usual way.
| 【1】 Ireland, C.; Leeson, P.A.; Castaner, J.; Lobucavir. Drugs Fut 1997, 22, 4, 359. |
| 【2】 Honjo, M.; Maruyama, T.; Sato, Y. (Nippon Kayaku Co., Ltd.); Production of carboxetanocin G or A and intermediates therefor. WO 9110665 . |
| 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) | 14380 | [(1S,2S)-2-[(benzoyloxy)methyl]-4-oxocyclobutyl]methyl benzoate | C20H18O5 | 详情 | 详情 | |
| (XXXI) | 14402 | [(1S,2R)-2-[(benzoyloxy)methyl]-3-(hydroxyimino)cyclobutyl]methyl benzoate | C20H19NO5 | 详情 | 详情 | |
| (XXXII) | 14403 | ((1S,2R,3R)-3-amino-2-[[(cyclohexylcarbonyl)oxy]methyl]cyclobutyl)methyl cyclohexanecarboxylate | C20H33NO4 | 详情 | 详情 | |
| (XXXIII) | 14404 | 4,6-dichloro-2-pyrimidinamine; 2-Amino-4,6-dichloropyrimidine; 4,6-dichloro-2-pyrimidinylamine | 56-05-3 | C4H3Cl2N3 | 详情 | 详情 |
| (XXXIV) | 14405 | ((1S,2R,3R)-3-[(2-amino-6-chloro-4-pyrimidinyl)amino]-2-[[(cyclohexylcarbonyl)oxy]methyl]cyclobutyl)methyl cyclohexanecarboxylate | C24H35ClN4O4 | 详情 | 详情 | |
| (XXXV) | 10197 | 4-Chlorobenzenediazonium chloride | C6H4Cl2N2 | 详情 | 详情 | |
| (XXXVI) | 14407 | ((1S,2R,3R)-3-([2-amino-6-chloro-5-[(E)-2-(4-chlorophenyl)diazenyl]-4-pyrimidinyl]amino)-2-[[(cyclohexylcarbonyl)oxy]methyl]cyclobutyl)methyl cyclohexanecarboxylate | C30H38Cl2N6O4 | 详情 | 详情 | |
| (XXXVII) | 14408 | [(1R,2S,4S)-2-[[(cyclohexylcarbonyl)oxy]methyl]-4-[(2,5-diamino-6-chloro-4-pyrimidinyl)amino]cyclobutyl]methyl cyclohexanecarboxylate | C24H36ClN5O4 | 详情 | 详情 | |
| (XXXVIII) | 14409 | ((1S,2R,3R)-3-(2-amino-6-chloro-9H-purin-9-yl)-2-[[(cyclohexylcarbonyl)oxy]methyl]cyclobutyl)methyl cyclohexanecarboxylate | C25H34ClN5O4 | 详情 | 详情 |