【结 构 式】 |
【药物名称】EPH-350 【化学名称】1-(5-Methylpyridin-2-yl)ethanone (1-methyl-1H-benzimidazol-2-yl)hydrazone 【CA登记号】379226-93-4 【 分 子 式 】C16H17N5 【 分 子 量 】279.34739 |
【开发单位】Universität Innsbruck (Originator) 【药理作用】Oncolytic Drugs |
合成路线1
3-Picoline (I) is oxidized to the corresponding N-oxide (II) by means of peracetic acid. Condensation of (II) with dimethylcarbamoyl chloride furnishes carbamate (III), which is then reacted with cyanotrimethylsilane, producing 2-cyano-5-methylpyridine (IV). Subsequent addition of methylmagnesium iodide to the cyanopyridine (IV) gives rise to the pyridyl ketone (V).
【1】 Easmon, J.; Fürtinger, S.; Lackner, G. ; Magreiter, E.; Hofmann, J.; Heinisch, G.; Puerstinger, G.; Hydrazones derived from monosubstitued 2-acetylpyridines and 2-hydrazino-1-methylbenzimidazole: Synthesis and biological studies. Eur J Cancer 2002, 38, Suppl. 7. |
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) | 62792 | 3-Methylpyridine; 3-Picoline | 108-99-6 | C6H7N | 详情 | 详情 |
(II) | 62793 | 3-Methyl-1-pyridiniumolate; 3-Picoline N-oxide | 1003-73-2 | C6H7NO | 详情 | 详情 |
(III) | 62794 | 1-{[(dimethylamino)carbonyl]oxy}-3-methylpyridinium chloride | C9H13ClN2O2 | 详情 | 详情 | |
(IV) | 38502 | 5-methyl-2-pyridinecarbonitrile | C7H6N2 | 详情 | 详情 | |
(V) | 62795 | 1-(5-methyl-2-pyridinyl)-1-ethanone | C8H9NO | 详情 | 详情 |
合成路线2
Alkylation of 2-chlorobenzimidazole (VI) with iodomethane and NaOH leads to 2-chloro-1-methylbenzimidazole (VII). The 2-chloro group of (VII) is then displaced with hydrazine hydrate to afford hydrazine (VIII). Finally, condensation between ketone (V) and hydrazine (VIII) gives rise to the target hydrazone.
【1】 Easmon, J.; Fürtinger, S.; Lackner, G. ; Magreiter, E.; Hofmann, J.; Heinisch, G.; Puerstinger, G.; Hydrazones derived from monosubstitued 2-acetylpyridines and 2-hydrazino-1-methylbenzimidazole: Synthesis and biological studies. Eur J Cancer 2002, 38, Suppl. 7. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(V) | 62795 | 1-(5-methyl-2-pyridinyl)-1-ethanone | C8H9NO | 详情 | 详情 | |
(VI) | 26761 | 2-chloroimidazo[1,2-a]pyridine; 2-chlorobenzimidazole; 2-Amino-4'-chlorodiphenylether; 2-Aminodiphenylether; 2-chloro-1H-benzimidazole | 4857-06-1 | C7H5ClN2 | 详情 | 详情 |
(VII) | 62796 | 2-chloro-1-methyl-1H-benzimidazole | C8H7ClN2 | 详情 | 详情 | |
(VIII) | 62797 | 2-hydrazino-1-methyl-1H-benzimidazole | C8H10N4 | 详情 | 详情 |