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【结 构 式】 
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【分子编号】14813 【品名】methyl 4-[(E)-4-methoxy-3-butenyl]benzoate 【CA登记号】 |
【 分 子 式 】C13H16O3 【 分 子 量 】220.26824 【元素组成】C 70.89% H 7.32% O 21.79% |
合成路线1
该中间体在本合成路线中的序号：(XXVIII)3) The silylation of 4-(3-formylpropyl)benzoic acid methyl ester (XXIII) with hexamethyldisilazane (HMSAZ) and trimethylsilyl iodide in dichloromethane gives the 4-(trimethylsilyloxy)-3-butenyl derivative (XXIV), which is brominated with Br2 in CCl4 yielding the 2-bromo-3-formylpropyl derivative (XXV). The cyclization of (XXV) with 2,4-diamino-6-hydroxypyrimidine (XXVI) by means of sodium acetate in methanol/water affords the 4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl] benzoic acid methyl ester (XXVII), which is saponified with NaOH to the corresponding free acid (XX) already obtained. The synthesis is then continued as in scheme 1735602a. 4) The benzoic ester (XXVII) can also be obtained by condensation of 4-(2-formylethyl)benzoic acid methyl ester (XIV) with methoxymethyltriphenylphosphonium bromide by means of potassium tert-butoxide in toluene giving 4-(4-methoxy-3-butenyl)benzoic acid methyl ester (XXVIII), which is then cyclized with 2,4-diamino-6-hydroxypyrimidine (XXVI) by means of Br2 in acetonitrile.
| 【1】 Castaner, J.; Graul, A.; Tracy, M.; Penetrexed Disodium. Drugs Fut 1998, 23, 5, 498. |
| 【2】 Barnett, C.J.; Wilson, T.M. (Eli Lilly and Company); Process for preparing 5-substd. pyrrolo[2,3-d]pyrimidines. EP 0589720; US 5416211 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIV) | 63842 | methyl 4-(3-oxopropyl)benzoate | C11H12O3 | 详情 | 详情 | |
| (XX) | 14805 | 4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid | C15H14N4O3 | 详情 | 详情 | |
| (XXIII) | 14808 | methyl 4-(4-oxobutyl)benzoate | C12H14O3 | 详情 | 详情 | |
| (XXIV) | 14809 | methyl 4-[(E)-4-[(trimethylsilyl)oxy]-3-butenyl]benzoate | C15H22O3Si | 详情 | 详情 | |
| (XXV) | 14810 | methyl 4-(2-bromo-4-oxobutyl)benzoate | C12H13BrO3 | 详情 | 详情 | |
| (XXVI) | 14811 | 2,4-Diamino-6-hydroxypyrimidine; 2,6-diamino-4-pyrimidinol | 56-06-4 | C4H6N4O | 详情 | 详情 |
| (XXVII) | 14812 | methyl 4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoate | C16H16N4O3 | 详情 | 详情 | |
| (XXVIII) | 14813 | methyl 4-[(E)-4-methoxy-3-butenyl]benzoate | C13H16O3 | 详情 | 详情 |