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【结 构 式】 
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【分子编号】61423 【品名】(3aR,4S,6R,6aR)-2,2-dimethyl-6-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid 【CA登记号】 |
【 分 子 式 】C13H14N4O6 【 分 子 量 】322.27752 【元素组成】C 48.45% H 4.38% N 17.38% O 29.79% |
合成路线1
该中间体在本合成路线中的序号：(I)The title compound is prepared by two methods. Chlorination of 2',3'-O-isopropylideneinosine-5'-uronic acid (I) with SOCl2 in the presence of DMF produces the chloropurine acid chloride (II), which is further converted into the amide (III) upon treatment with ethylamine. Subsequent displacement of the purine 6-chloro group of (III) with cyclopentylamine (IV) furnishes the cyclopentylamino purine (V). Finally, acidic ketal hydrolysis in (IV) gives rise to the target compound.
| 【1】 Olsson, R.A.; Thompson, R.D. (UCB Pharma, Inc.); N-6 Substd.-5'-(N-substd. carboxamido)adenosines as cardiac vasodilators and antihypertensive agents. AU 8544972; EP 0191025; ES 8609359; JP 1986286398; US 5310731; WO 8600310 . |
| 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) | 61423 | (3aR,4S,6R,6aR)-2,2-dimethyl-6-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid | C13H14N4O6 | 详情 | 详情 | |
| (II) | 61424 | (3aR,4S,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carbonyl chloride | C13H12Cl2N4O4 | 详情 | 详情 | |
| (III) | 61425 | (3aR,4S,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-N-ethyl-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxamide | C15H18ClN5O4 | 详情 | 详情 | |
| (IV) | 28850 | cyclopentanamine | 1003-03-8 | C5H11N | 详情 | 详情 |
| (V) | 61426 | (3aR,4S,6R,6aR)-6-[6-(cyclopentylamino)-9H-purin-9-yl]-N-ethyl-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxamide | C20H28N6O4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Alternatively, the inosine uronic acid (I) is converted to ethyl ester (II) by sequential treatment with thionyl chloride and then ethanol. Subsequent reaction with acetic anhydride in pyridine gives rise to diacetate (III). Chlorination of the inosine ring of (III) to produce (IV) is accomplished by treatment with phosphoryl chloride in the presence of tetraethylammonium chloride. Displacement of the 6-chloro group of (IV) with cyclopentylamine (V) yields amino purine (VI). Finally, aminolysis of the ester groups of (VI) with ethanolic ethylamine leads to the title compound.
| 【1】 Hamilton, H.W.; Patt, W.C. (Pfizer Inc.); N6-Substd.-5'-oxidized adenosine analogs. EP 0222330; JP 1987111996; US 4738954 . |
| 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) | 61423 | (3aR,4S,6R,6aR)-2,2-dimethyl-6-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid | C13H14N4O6 | 详情 | 详情 | |
| (II) | 61427 | ethyl (3aR,4S,6R,6aR)-2,2-dimethyl-6-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylate | C15H18N4O6 | 详情 | 详情 | |
| (III) | 61428 | ethyl (2S,3R,4R,5R)-3,4-bis(acetyloxy)-5-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydro-2-furancarboxylate | C16H18N4O8 | 详情 | 详情 | |
| (IV) | 61429 | ethyl (2S,3R,4R,5R)-3,4-bis(acetyloxy)-5-(6-chloro-9H-purin-9-yl)tetrahydro-2-furancarboxylate | C16H17ClN4O7 | 详情 | 详情 | |
| (V) | 28850 | cyclopentanamine | 1003-03-8 | C5H11N | 详情 | 详情 |
| (VI) | 61430 | ethyl (2S,3R,4R,5R)-3,4-bis(acetyloxy)-5-[6-(cyclopentylamino)-9H-purin-9-yl]tetrahydro-2-furancarboxylate | C21H27N5O7 | 详情 | 详情 |