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【结 构 式】 
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【分子编号】45882 【品名】4-[(7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)(propyl)amino]-1-butanol 【CA登记号】 |
【 分 子 式 】C25H36N4O 【 分 子 量 】408.5872 【元素组成】C 73.49% H 8.88% N 13.71% O 3.92% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Condensation of 2,4,6-trimethylaniline (I) with malononitrile derivative (II) in isopropanol yields carbonitrile (III), which is then acetylated by means of Ac2O in HOAc to provide acetamide (IV). Cyclization of (IV) is induced by treatment with phosphoric acid to furnish pyrimidinone (V), which is then converted into chloro derivative (VI) in refluxing POCl3 (1). Coupling of (VI) with secondary amine (VII) in DMSO affords compound (VIII), which is finally fluorinated by treatment with tetrabutylammonium fluoride (TBAF) and toluenesulfonyl fluoride (TsF) in refluxing THF.
| 【1】 Chen, Y.L. (Pfizer Inc.); Pyrrolopyrimidines as CRF antagonists. EP 0674641; JP 1995509726; WO 9413676 . |
| 【2】 Chrousos, G.P.; Rice, K.C.; Hsin, L.-W.; Gold, P.W.; Webster, E.L.; Contoreggi, C.; Eckelman, W.C.; Synthesis and biological activity of fluoro-substituted pyrrolo[2,3-d]pyrimidines: The development of potential positron emission tomography imaging agents for the corticotropin-releasing hormone type 1 receptor. Bioorg Med Chem Lett 2000, 10, 8, 707. |
| 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) | 28804 | 2,4,6-trimethylaniline | 88-05-1 | C9H13N | 详情 | 详情 |
| (II) | 45876 | 2-(2-bromo-1-methylpropylidene)malononitrile | C7H7BrN2 | 详情 | 详情 | |
| (III) | 45877 | 2-amino-1-mesityl-4,5-dimethyl-1H-pyrrole-3-carbonitrile | C16H19N3 | 详情 | 详情 | |
| (IV) | 45878 | N-(3-cyano-1-mesityl-4,5-dimethyl-1H-pyrrol-2-yl)acetamide | C18H21N3O | 详情 | 详情 | |
| (V) | 45879 | 7-mesityl-2,5,6-trimethyl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one | C18H21N3O | 详情 | 详情 | |
| (VI) | 45880 | 4-chloro-7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidine | C18H20ClN3 | 详情 | 详情 | |
| (VII) | 45881 | 4-(propylamino)-1-butanol | C7H17NO | 详情 | 详情 | |
| (VIII) | 45882 | 4-[(7-mesityl-2,5,6-trimethyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)(propyl)amino]-1-butanol | C25H36N4O | 详情 | 详情 |