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【结 构 式】 
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【分子编号】64873 【品名】5-(bromomethyl)-2,4-pyrimidinediamine 【CA登记号】 |
【 分 子 式 】C5H7BrN4 【 分 子 量 】203.04154 【元素组成】C 29.58% H 3.47% Br 39.35% N 27.59% |
合成路线1
该中间体在本合成路线中的序号：(VI)Condensation of guanidine nitrate (I) with (ethoxymethylene)malononitrile (II) in the presence of NaOEt yields 2,4-diaminopyrimidine-5-carbonitrile (III). Reduction of nitrile (III) by means of Raney nickel in formic acid leads to aldehyde (IV), which is further reduced to alcohol (V) by means of NaBH4. Treatment of alcohol (V) with HBr in AcOH gives the bromide (VI), which is condensed with pyridine in DMF to form the crystalline pyridinium salt (VII). Finally, displacement of compound (VII) with the tetrahydroisoquinoline (VIII), followed by resolution by chiral HPLC, furnishes the title compound.
| 【1】 Gerber, P.; Wyss, P.C.; Hartman, P.G.; Hubschwerlen, C.; Locher, H.; Marty, H.-P.; Stahl, M.; Novel dihydrofolate reductase inhibitors. Structure-based versus diversity-based library design and high-throughput synthesis and screening. J Med Chem 2003, 46, 12, 2304. |
| 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) | 14790 | Guanidine | 113-00-8 | CH5N3 | 详情 | 详情 |
| (II) | 13017 | Ethoxymethylenemalononitrile; 2-(Ethoxymethylene)malononitrile | 123-06-8 | C6H6N2O | 详情 | 详情 |
| (III) | 64871 | 2,4-diamino-5-pyrimidinecarbonitrile | C5H5N5 | 详情 | 详情 | |
| (IV) | 26525 | 2,4-diamino-5-pyrimidinecarbaldehyde | C5H6N4O | 详情 | 详情 | |
| (V) | 64872 | (2,4-diamino-5-pyrimidinyl)methanol | C5H8N4O | 详情 | 详情 | |
| (VI) | 64873 | 5-(bromomethyl)-2,4-pyrimidinediamine | C5H7BrN4 | 详情 | 详情 | |
| (VII) | 64874 | 1-[(2,4-diamino-5-pyrimidinyl)methyl]pyridinium bromide | C10H12BrN5 | 详情 | 详情 | |
| (VIII) | 64875 | methyl 9-methyl-6,7,8,9-tetrahydro[1,3]dioxolo[4,5-h]isoquinolin-4-yl ether; 9-methyl-4-(methyloxy)-6,7,8,9-tetrahydro[1,3]dioxolo[4,5-h]isoquinoline | C12H15NO3 | 详情 | 详情 |