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【结 构 式】 
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【药物名称】 【化学名称】5-(3-Chlorophenyl)-6-[1-(4-cyanophenyl)-1-(1-methyl-1H-imidazol-5-yl)methoxymethyl]-2-oxo-1,2-dihydropyridine-3-carbonitrile 【CA登记号】 【 分 子 式 】C25H18ClN5O2 【 分 子 量 】455.90751 |
【开发单位】Abbott (Originator) 【药理作用】Oncolytic Drugs, Farnesyl Transferase Inhibitors |
合成路线1
Bromination of 3-cyano-6-methyl-2-pyridone (I) by means of N bromosuccinimide (NBS) in 1,2-dichloroethane affords the 5-bromopyridone (II). Subsequent Suzuki coupling of (II) with 3-chlorophenylboronic acid (III) yields the 5-phenylpyridone (IV). Radical bromination of (IV) with NBS and AIBN produces the bromomethyl derivative (V). This is then converted to alcohol (VI) upon refluxing in aqueous dioxane in the presence of celite
| 【1】 Hasvold, L.A.; et al.; Design and synthesis of pyridone farnesyltransferase inhibitors. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 126. |
| 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) | 27560 | 6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile | 4241-27-4 | C7H6N2O | 详情 | 详情 |
| (II) | 60859 | 5-bromo-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile | C7H5BrN2O | 详情 | 详情 | |
| (III) | 39759 | 3-chlorophenylboronic acid | 63503-60-6 | C6H6BClO2 | 详情 | 详情 |
| (IV) | 60860 | 5-(3-chlorophenyl)-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile | C13H9ClN2O | 详情 | 详情 | |
| (V) | 60861 | 6-(bromomethyl)-5-(3-chlorophenyl)-2-oxo-1,2-dihydro-3-pyridinecarbonitrile | C13H8BrClN2O | 详情 | 详情 | |
| (VI) | 60862 | 5-(3-chlorophenyl)-6-(hydroxymethyl)-2-oxo-1,2-dihydro-3-pyridinecarbonitrile | C13H9ClN2O2 | 详情 | 详情 |
合成路线2
Lithiation of 1-methylimidazole (VII), followed by quenching with triethylchlorosilane provides the 2-silyl imidazole (VIII). After metalation of (VIII) with tert-butyllithium, condensation with 4-cyanobenzaldehyde (IX) gives rise to the carbinol (X). Finally, coupling between alcohols (VI) and (X) in the presence of p-toluenesulfonic acid in refluxing toluene leads to the desired ether adduct.
| 【1】 Hasvold, L.A.; et al.; Design and synthesis of pyridone farnesyltransferase inhibitors. 224th ACS Natl Meet (Aug 18 2002, Boston) 2002, Abst MEDI 126. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 60862 | 5-(3-chlorophenyl)-6-(hydroxymethyl)-2-oxo-1,2-dihydro-3-pyridinecarbonitrile | C13H9ClN2O2 | 详情 | 详情 | |
| (VII) | 38630 | 1-methyl-1H-imidazole | 616-47-7 | C4H6N2 | 详情 | 详情 |
| (VIII) | 60863 | 1-methyl-2-(tripropylsilyl)-1H-imidazole | C13H26N2Si | 详情 | 详情 | |
| (IX) | 17552 | 4-formylbenzonitrile; 4-Cyanobenzaldehyde | 105-07-7 | C8H5NO | 详情 | 详情 |
| (X) | 60864 | 4-[hydroxy(1-methyl-1H-imidazol-2-yl)methyl]benzonitrile | C12H11N3O | 详情 | 详情 |