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【结 构 式】 
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【分子编号】21764 【品名】[2-[(Z)-(6-amino-9H-purin-9-yl)methylidene]cyclopropyl]methyl benzoate 【CA登记号】 |
【 分 子 式 】C17H15N5O2 【 分 子 量 】321.3386 【元素组成】C 63.54% H 4.71% N 21.79% O 9.96% |
合成路线1
该中间体在本合成路线中的序号：(XVII)A related synthesis for the racemic compound (IX) has been reported. This involves initial reduction of the diasteromeric esters (III) and (IV) to the corresponding alcohols (XIII) with DIBALH. The hydroxyl group of (XIII) was then protected as either the benzoate ester (XIV) with benzoyl bromide in pyridine, or as the methoxymethyl (MOM) ether, using chloromethyl methyl ether and diisopropyl ethylamine, which furnished dibromo- (XV) along with bromochlorocompound (XVI). The alkylation-elimination reaction of dibromide (XIV) using adenine (V) and K2CO3 in DMF at 95 C gave an unseparable mixture of Z- (XVII) and E- (XVIII) methylene cyclopropanes. The benzoate esters (XVII) + (XVIII) were then deprotected in methanolic ammonia to afford a mixture of the target racemic Z-olefin (IX) and its E-isomer (X). In contrast, the alkylation-elimination products (XIX) and (XX) from the MOM-protected halides (XV) + (XVI) could be separed by chromatography. Deprotection of the desired Z-isomer (XX) with methanolic HCl provided racemic (IX).
| 【1】 Qiu, Y.-L.; et al.; (Z)- and (E)-2-((Hydroxymethyl)cyclopropylidene)methyladenine and -guanine. New nucleoside analogues with a broad-spectrum antiviral activity. J Med Chem 1998, 41, 1, 10. |
| 【2】 Qiu, Y.-L.; Hempel, A.; Camerman, N.; Camerman, A.; Geiser, F.; Ptak, R.G.; Breitenbach, J.M.; Kira, T.; Li, L.; Gullen, E.; Cheng, Y.C.; Drach, J.C.; Zemlicka, J.; (R)-(-)- and (S)-(+)-synadenol: Synthesis, absolute configuration, and enantioselectivity of antiviral effect. J Med Chem 1998, 41, 26, 5257. |
| 【3】 Zemilicka, J.; Qiu, Y.-L.; A new efficient synthesis of antiviral methylenecyclopropane analogs of purine nucleosides. Synthesis 1998, 10, 1447-1452. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 21750 | ethyl (1S,2R)-2-bromo-2-(bromomethyl)cyclopropanecarboxylate | C7H10Br2O2 | 详情 | 详情 | |
| (IV) | 21751 | ethyl (1S,2S)-2-bromo-2-(bromomethyl)cyclopropanecarboxylate | C7H10Br2O2 | 详情 | 详情 | |
| (IX) | 21756 | [2-[(Z)-(6-amino-9H-purin-9-yl)methylidene]cyclopropyl]methanol | C10H11N5O | 详情 | 详情 | |
| (X) | 21757 | [2-[(E)-(6-amino-9H-purin-9-yl)methylidene]cyclopropyl]methanol | C10H11N5O | 详情 | 详情 | |
| (XIII) | 21760 | [2-bromo-2-(bromomethyl)cyclopropyl]methanol | C5H8Br2O | 详情 | 详情 | |
| (XIV) | 21761 | [2-bromo-2-(bromomethyl)cyclopropyl]methyl benzoate | C12H12Br2O2 | 详情 | 详情 | |
| (XV) | 21762 | 1-bromo-1-(bromomethyl)-2-[(methoxymethoxy)methyl]cyclopropane; [[2-bromo-2-(bromomethyl)cyclopropyl]methoxy]methyl methyl ether | C7H12Br2O2 | 详情 | 详情 | |
| (XVI) | 21763 | 1-bromo-1-(chloromethyl)-2-[(methoxymethoxy)methyl]cyclopropane | C7H12BrClO2 | 详情 | 详情 | |
| (XVII) | 21764 | [2-[(Z)-(6-amino-9H-purin-9-yl)methylidene]cyclopropyl]methyl benzoate | C17H15N5O2 | 详情 | 详情 | |
| (XVIII) | 21765 | [2-[(E)-(6-amino-9H-purin-9-yl)methylidene]cyclopropyl]methyl benzoate | C17H15N5O2 | 详情 | 详情 | |
| (XIX) | 21766 | 9-([2-[(methoxymethoxy)methyl]cyclopropylidene]methyl)-9H-purin-6-ylamine; 9-([2-[(methoxymethoxy)methyl]cyclopropylidene]methyl)-9H-purin-6-amine | C12H15N5O2 | 详情 | 详情 | |
| (XX) | 21767 | 9-([2-[(methoxymethoxy)methyl]cyclopropylidene]methyl)-9H-purin-6-amine; 9-([2-[(methoxymethoxy)methyl]cyclopropylidene]methyl)-9H-purin-6-ylamine | C12H15N5O2 | 详情 | 详情 |