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【结 构 式】 
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【药物名称】CDD-0102 【化学名称】5-(3-Ethyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine 【CA登记号】146422-58-4 【 分 子 式 】C8H12N4O 【 分 子 量 】180.21104 |
【开发单位】Cognitive Pharmaceuticals (Originator), University of Toledo (Originator) 【药理作用】Alzheimer's Dementia, Treatment of , Cognition Disorders, Treatment of, NEUROLOGIC DRUGS, Muscarinic M1 Agonists |
合成路线1
Lithiation of 5-bromopyrimidine (I), followed by addition of CO2 produces pyrimidine-5-carboxylic acid (II). After catalytic hydrogenation of (II), the resultant tetrahydropyrimidine acid (III) is esterified with SOCl2 in MeOH to yield the corresponding methyl ester (IV). Protection of (IV) with triphenylmethyl chloride and DBU affords the N-trityl derivative (V). Then, condensation between the sodium derivative of propionamide oxime (VI) and ester (V) gives rise to the oxadiazole compound (VII). The N-trityl group of (VII) is finally removed with trifluoroacetic acid to furnish the title compound.
| 【1】 Dunbar, P.G.; Durant, G.J.; Fang, Z.; Abuh, Y.F.; El-Assadi, A.A.; Ngur, D.O.; Periyasamy, S.; Hoss, W.P.; Messer, W.S. Jr.; Design, synthesis, and neurochemical evaluation of 5-(3-alkyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidines as M1 muscarinic receptor agonists. J. Med. Chem. 1993, 36, 7, 842. |
| 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) | 38987 | 5-bromopyrimidine | 4595-59-9 | C4H3BrN2 | 详情 | 详情 |
| (II) | 61334 | 5-pyrimidinecarboxylic acid | C5H4N2O2 | 详情 | 详情 | |
| (III) | 61335 | 1,4,5,6-tetrahydro-5-pyrimidinecarboxylic acid | C5H8N2O2 | 详情 | 详情 | |
| (IV) | 61336 | methyl 1,4,5,6-tetrahydro-5-pyrimidinecarboxylate | C6H10N2O2 | 详情 | 详情 | |
| (V) | 61337 | methyl 1-trityl-1,4,5,6-tetrahydro-5-pyrimidinecarboxylate | C25H24N2O2 | 详情 | 详情 | |
| (VI) | 61338 | N'-hydroxypropanimidamide | C3H8N2O | 详情 | 详情 | |
| (VII) | 61339 | 5-(3-ethyl-1,2,4-oxadiazol-5-yl)-1-trityl-1,4,5,6-tetrahydropyrimidine | C27H26N4O | 详情 | 详情 |