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【结 构 式】 
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【分子编号】57603 【品名】2-bromo-3-methyl-1-pyridiniumolate 【CA登记号】 |
【 分 子 式 】C6H6BrNO 【 分 子 量 】188.02378 【元素组成】C 38.33% H 3.22% Br 42.5% N 7.45% O 8.51% |
合成路线1
该中间体在本合成路线中的序号：(II)2-Bromo-3-methylpyridine (I) is converted to the corresponding N-oxide (II) by treatment with m-chloroperbenzoic acid in CH2Cl2. Reaction of N-oxide (II) with trimethylsilyl cyanide and dimethylcarbamoyl chloride gives rise to the 2-cyanopyridine (III). Subsequent radical bromination of (III) using NBS and AIBN affords the bromomethyl pyridine (IV). Lithiation of 1-methyl-2-(triethylsilyl)imidazole (V), followed by condensation with 4-cyanobenzaldehyde (VI), provides carbinol (VII). This is then condensed with bromide (IV) in the presence of Ag2O to give ether (VIII). 5-Bromo-2,2-difluorobenzodioxole (IX) is lithiated with butyllithium in cold Et2O and subsequently treated with triisopropyl borate to afford, after aqueous work-up, the arylboronic acid (X). Finally, Mitsunobu coupling between boronic acid (X) and the bromopyridine (VIII) provides the title compound.
| 【1】 Wang, L.; Hasvold, L.; Tong, Y.; et al.; Discovery of potent and orally active farnesyltransferase inhibitors. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 129. |
| 【2】 Sham, H.L.; Rockway, T.W.; Li, T.; Mantei, R.A.; Li, Q.; Lin, N.-H.; Wang, L.; Wang, W.; Wang, X.; Sullivan, G.M.; Wang, G.T.; Gwaltney, S.L. II; Claiborne, A.K.; Hasvold, L.A.; Tong, Y. (Abbott Laboratories Inc.); Farnesyltransferase inhibitors. US 2002115640; WO 0274747 . |
| 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) | 57602 | 2-Bromo-3-methylpyridine; 2-Bromo-3-picoline | 3430-17-9 | C6H6BrN | 详情 | 详情 |
| (II) | 57603 | 2-bromo-3-methyl-1-pyridiniumolate | C6H6BrNO | 详情 | 详情 | |
| (III) | 57604 | 6-bromo-5-methyl-2-pyridinecarbonitrile | C7H5BrN2 | 详情 | 详情 | |
| (IV) | 57605 | 6-bromo-5-(bromomethyl)-2-pyridinecarbonitrile | C7H4Br2N2 | 详情 | 详情 | |
| (V) | 57606 | 1-methyl-5-(triethylsilyl)-1H-imidazole | C10H20N2Si | 详情 | 详情 | |
| (VI) | 17552 | 4-formylbenzonitrile; 4-Cyanobenzaldehyde | 105-07-7 | C8H5NO | 详情 | 详情 |
| (VII) | 57607 | 4-[hydroxy(1-methyl-1H-imidazol-5-yl)methyl]benzonitrile | C12H11N3O | 详情 | 详情 | |
| (VIII) | 57608 | 6-bromo-5-{[(4-cyanophenyl)(1-methyl-1H-imidazol-5-yl)methoxy]methyl}-2-pyridinecarbonitrile | C19H14BrN5O | 详情 | 详情 | |
| (IX) | 57609 | 5-Bromo-2,2-difluoro-1,3-benzodioxole；4-Bromo-1,2-[(difluoromethylene)dioxy]benzene | 33070-32-5 | C7H3BrF2O2 | 详情 | 详情 |
| (X) | 57610 | 2,2-difluoro-1,3-benzodioxol-5-ylboronic acid | C7H5BF2O4 | 详情 | 详情 |