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【结 构 式】 
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【分子编号】14804 【品名】Ethyl 4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoate 【CA登记号】 |
【 分 子 式 】C17H18N4O3 【 分 子 量 】326.35508 【元素组成】C 62.57% H 5.56% N 17.17% O 14.71% |
合成路线1
该中间体在本合成路线中的序号：(XIX)2) The reaction of 4-(2-formylethyl)benzoic acid ethyl ester (XIV) with paraformaldehyde (XV) by means of N-ethylbenzothiazolium bromide (XVI) and triethylamine gives the 4-hydroxy-3-oxobutyl derivative (XVII), which is condensed with ethyl cyanoacetate (I) by means of triethylamine in ethanol yielding the furancarboxylate derivative (XVIII). The cyclization of (XVIII) with guanidine (IV) by means of sodium ethoxide in ethanol affords 4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl] benzoic acid ethyl ester (XIX), which is saponified with NaOH to the corresponding free acid (XX). The condensation of (XX) with L-glutamic acid diethyl ester (XXI) in the usual way affords the diethyl ester of LY-231514 (XXII), which is finally saponified with NaOH.
| 【1】 Castaner, J.; Graul, A.; Tracy, M.; Penetrexed Disodium. Drugs Fut 1998, 23, 5, 498. |
| 【2】 Taylor, E.C.; Patel, H.H. (Princeton University); Process for the preparation of pyrrolo[2,3-d]pyrimidines. CA 2084490 . |
| 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) | 11877 | Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate | 105-56-6 | C5H7NO2 | 详情 | 详情 |
| (IV) | 14470 | 2-[(4R)-3,4-dihydro-2H-chromen-4-yl]-N-[(1R)-2-hydroxy-1-phenylethyl]acetamide | C19H21NO3 | 详情 | 详情 | |
| (XIV) | 14800 | ethyl 4-(3-oxopropyl)benzoate | C12H14O3 | 详情 | 详情 | |
| (XVI) | 14801 | 3-Ethylbenzothiazolium bromide; 3-Ethyl-1,3-benzothiazol-3-ium bromide | 32446-47-2 | C9H10BrNS | 详情 | 详情 |
| (XVII) | 14802 | Ethyl 4-(4-hydroxy-3-oxobutyl)benzoate | C13H16O4 | 详情 | 详情 | |
| (XVIII) | 14803 | Ethyl 2-amino-4-[4-(ethoxycarbonyl)phenethyl]-3-furoate | C18H21NO5 | 详情 | 详情 | |
| (XIX) | 14804 | Ethyl 4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoate | C17H18N4O3 | 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 | |
| (XXI) | 11013 | diethyl (2S)-2-aminopentanedioate | C9H17NO4 | 详情 | 详情 | |
| (XXII) | 14807 | diethyl (2S)-2-([4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino)pentanedioate | C24H29N5O6 | 详情 | 详情 |