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【结 构 式】 
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【分子编号】65896 【品名】1-(5-Pyrimidinyl)ethanone; 5-Acetylpyrimidine 【CA登记号】10325-70-9 |
【 分 子 式 】C6H6N2O 【 分 子 量 】122.12652 【元素组成】C 59.01% H 4.95% N 22.94% O 13.1% |
合成路线1
该中间体在本合成路线中的序号：(I)Heating of 5-acetylpyrimidine (I) with N,N-dimethylformamide dimethylacetal (II) affords 3-(dimethylamino)-1-(5-pyrimidinyl)-2-propen-1-one (III), which is cyclized with 1-(2-methyl-5-nitrophenyl)guanidine —prepared in situ by adding NaOH to the guanidine nitrate (IV) in 2-propanol at 120 °C— to provide 1-methyl-4-nitro-2-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]benzene (V). The nitro group of compound (V) is then reduced to the corresponding aniline (VI) by catalytic transfer hydrogenation in the presence of formic acid and Pd/C in THF/MeOH. Benzylic bromination of 4-methyl-3-(trifluoromethyl)benzoic acid (VII) using sodium bromate and sodium bisulfite in isopropyl acetate gives 4-(bromomethyl)-3-(trifluoromethyl)benzoic acid (VIII), which is converted to the acid chloride (IX) by treatment with (COCl)2 and catalytic DMF in CH2Cl2. Acid chloride (IX) is then coupled with aniline (VI) in the presence of K2CO3 in dioxane to yield the 4-(bromomethyl)benzamide (X), from which the bromide group is finally displaced with (–)-(S)-3-(dimethylamino)pyrrolidine (XI) in the presence of K2CO3 in anhydrous DMF (1, 2). Scheme 1
| 【1】 Asaki, T., Sugiyama, Y., Hamamoto, T., Higashioka, M., Umehara, M., Naito, H., Niwa, T. Design and synthesis of 3-substituted benzamide derivatives as Bcr-Abl kinase inhibitors. Bioorg Med Chem Lett 2006, 16(5): 1421-5. |
| 【2】 Asaki, T., Sugiyama, Y., Segawa, J. (Nippon Shinyaku Co., Ltd.). Amide derivative and medicine. EP 1702917, US 2008293940, WO 2005063709. |
| 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) | 65896 | 1-(5-Pyrimidinyl)ethanone; 5-Acetylpyrimidine | 10325-70-9 | C6H6N2O | 详情 | 详情 |
| (II) | 11984 | N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal | 4637-24-5 | C5H13NO2 | 详情 | 详情 |
| (III) | 65897 | 3-(Dimethylamino)-1-(5-pyrimidinyl)-2-propen-1-one | 641615-34-1 | C9H11N3O | 详情 | 详情 |
| (IV) | 65898 | (2-Methyl-5-nitrophenyl)guanidine nitrate; N-(2-Methyl-5-nitrophenyl)guanidine nitrate | 152460-08-7 | C8H10N4O2.HNO3 | 详情 | 详情 |
| (V) | 65899 | 2-Methyl-5-nitro-N-[4-(5-pyrimidinyl)pyrimidin-2-yl]aniline | C15H12N6O2 | 详情 | 详情 | |
| (VI) | 65900 | 4-Methyl-N-3-(4-(pyrimidin-5-yl)pyrimidin-2-yl)benzene-1,3-diamine; 4-Methyl-3-[4-(5-pyrimidinyl)pyrimidin-2-ylamino]aniline | 641615-36-3 | C15H14N6 | 详情 | 详情 |
| (VII) | 65901 | 4-Methyl-3-(trifluoromethyl)benzoic acid | 261952-01-6 | C9H7F3O2 | 详情 | 详情 |
| (VIII) | 65902 | 4-Bromomethyl-3-(trifluoromethyl)benzoic acid | C9H6BrF3O2 | 详情 | 详情 | |
| (IX) | 65903 | 4-Bromomethyl-3-trifluoromethylbenzoyl chloride | 948553-14-8 | C9H5BrClF3O | 详情 | 详情 |
| (X) | 65904 | C24H18BrF3N6O | 详情 | 详情 | ||
| (XI) | 65905 | (3S)-N,N-dimethyl-3-pyrrolidinamine; N,N-dimethyl-N-[(3S)pyrrolidinyl]amine | 132883-44-4 | C6H14N2 | 详情 | 详情 |