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【结 构 式】 
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【分子编号】41033 【品名】N-(5-nitroso-2,6-dioxo-1,3-dipropyl-1,2,3,6-tetrahydro-4-pyrimidinyl)cyclopentanecarboxamide 【CA登记号】 |
【 分 子 式 】C16H24N4O4 【 分 子 量 】336.39112 【元素组成】C 57.13% H 7.19% N 16.66% O 19.02% |
合成路线1
该中间体在本合成路线中的序号：(VII)CPX has been obtained by two related ways: 1) Nitrosation of 6-amino-1,3-dipropyluracil (I) with NaNO2 in acetic acid gives the 5-nitrosouracil derivative (II), which is reduced with H2 over Pd/C in ethanol to yield 5,6-diamino-1,3-dipropyluracil (III). Acylation of (III) with cyclopentanecarboxylic acid (IV) by heating up to the mixture's melting point or by treatment with diisopropylcarbodiimide (DIC) gives the amide (V), which is finally cyclized by means of NaOH in refluxing water or refluxing methanol/water. 2) Acylation of the 5-nitrosouracil (II) with cyclopentanecarbonyl chloride (VI) by means of lithium hexamethyldisilazane (LHMDS) in THF gives the amide (VII), which is submitted to a reductive cyclization with Sn(OAc)2 in the same solvent.
| 【1】 Castaner, J.; Martin, L.; Sorbera, L.A.; CPX. Drugs Fut 2000, 25, 10, 1011. |
| 【2】 Hiner, R.N.; Rzeszotarski, W.J.; Hicks, R.P.; Costello, D.G.; Feeney, S.W.; Blake, P.R.; Erickson, R.H.; Abreu, M.E.; 1,3,8-Trisubstituted xanthines. Effects of substitution pattern upon adenosine receptor A1/A2 affinity. J Med Chem 1991, 34, 4, 1431. |
| 【3】 Schow, S.R.; Lum, R.T.; Melville, C.R.; Nelson, M.G.; Moore, A.G.; Convenient one-pot synthesis of xanthines from 6-amino-5-nitrosouracils. Synthesis 1999, 7, 1123. |
| 【4】 Hong, O.; Ukena, D.; Padgett, W.L.; Daly, J.W.; Shamim, M.T.; 8-Aryl- and 8-cycloalkyl-1,3-dipropylxanthines: Further potent and selective antagonists for A1-adenosine receptors. J Med Chem 1988, 31, 3, 613. |
| 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) | 41030 | 6-amino-1,3-dipropyl-2,4(1H,3H)-pyrimidinedione | 41862-14-0 | C10H17N3O2 | 详情 | 详情 |
| (II) | 41031 | 6-amino-5-nitroso-1,3-dipropyl-2,4(1H,3H)-pyrimidinedione | C10H16N4O3 | 详情 | 详情 | |
| (III) | 14628 | 5,6-diamino-1,3-dipropyl-2,4(1H,3H)-pyrimidinedione | C10H18N4O2 | 详情 | 详情 | |
| (IV) | 20734 | cyclopentanecarboxylic acid | 3400-45-1 | C6H10O2 | 详情 | 详情 |
| (V) | 41034 | N-(6-amino-2,4-dioxo-1,3-dipropyl-1,2,3,4-tetrahydro-5-pyrimidinyl)cyclopentanecarboxamide | C16H26N4O3 | 详情 | 详情 | |
| (VI) | 41032 | cyclopentanecarbonyl chloride | 4524-93-0 | C6H9ClO | 详情 | 详情 |
| (VII) | 41033 | N-(5-nitroso-2,6-dioxo-1,3-dipropyl-1,2,3,6-tetrahydro-4-pyrimidinyl)cyclopentanecarboxamide | C16H24N4O4 | 详情 | 详情 |