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【结 构 式】 
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【分子编号】26314 【品名】5-amino-1H-benzimidazol-2-ylhydrosulfide; 5-amino-1H-benzimidazole-2-thiol 【CA登记号】 |
【 分 子 式 】C7H7N3S 【 分 子 量 】165.2188 【元素组成】C 50.89% H 4.27% N 25.43% S 19.41% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The synthesis of IY-81149 can be obtained according to Scheme 22875502a. The oxidation of 2,3-lutidine (I) with hydrogen peroxide in acetic acid affords 2,3-dimethylpyridine-N-oxide (II), which is treated with sulfuric acid and nitric acid to give the corresponding nitro compound (III). The treatment of (III) with NaOH in methanol gives 2,3-dimethyl-4-methoxypyridine-N-oxide (IV), which is reacted with acetic acid and acetic anhydride and oxidized in refluxing NaOH, yielding 3-methyl-4-methoxypyridine-2-methanol (V). The chlorination of (V) with thionylchloride in CH2Cl2 affords 3-methyl-4-methoxy-2-chloromethylpyridine (VI). The reaction of 2-mercapto-5-nitrobenzimidazole (VII) with iron and concentrated HCl in refluxing ethanol and water gives monoamine (VIII), which by condensation with 2,5-dimethoxytetrahydrofuran (IX) in acetic acid yields 2-mercapto-5-(1-pyrrolyl)benzimidazole (X). The condensation of (VI) with (X) by means of NaOH in methanol gives 2-[(4-methoxy-3-methyl-2-pyridinyl)methylsulfanyl]-5-(1H-pyrrol-1-yl)-1H-benzimidazole (XI), which is finally treated with m-chloroperoxybenzoic acid (m-CPBA) in chloroform.
| 【1】 Lee, S.M.; Jung, W.T.; Kim, D.Y.; IY-81149. Drugs Fut 1999, 24, 6, 618. |
| 【2】 Kohl, B.; Sturm, E.; Senn-Bilfinger, J.; Simon, W.A.; Krüger, U.; Schaefer, H.; Rainer, G.; Figala, V.; Klemm, K.; (H+,K+)-ATPase inhibiting 2-[(2-pyridylmethyl)sulfinyl]benzimidazoles. 4. A novel series of dimethoxypyridyl-substituted inhibitors with enhanced selectivity. The selection of pantoprazole as a clinical candidate. J Med Chem 1992, 35, 6, 1049. |
| 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) | 26309 | 2,3-Dimethylpyridine | 583-61-9 | C7H9N | 详情 | 详情 |
| (II) | 26310 | 2,3-dimethyl-1-pyridiniumolate | C7H9NO | 详情 | 详情 | |
| (III) | 19482 | 2,3-dimethyl-4-nitro-1-pyridiniumolate | 37699-43-7 | C7H8N2O3 | 详情 | 详情 |
| (IV) | 26311 | 4-methoxy-2,3-dimethyl-1-pyridiniumolate | C8H11NO2 | 详情 | 详情 | |
| (V) | 26312 | (4-methoxy-3-methyl-2-pyridinyl)methanol | C8H11NO2 | 详情 | 详情 | |
| (VI) | 20172 | 2-(chloromethyl)-4-methoxy-3-methylpyridine; 2-(chloromethyl)-3-methyl-4-pyridinyl methyl ether | C8H10ClNO | 详情 | 详情 | |
| (VII) | 26313 | 5-nitro-1H-benzimidazol-2-ylhydrosulfide; 2-Mercapto-5-nitrobenzimidazole; 5-nitro-1H-benzimidazole-2-thiol | 34202-69-2 | C7H5N3O2S | 详情 | 详情 |
| (VIII) | 26314 | 5-amino-1H-benzimidazol-2-ylhydrosulfide; 5-amino-1H-benzimidazole-2-thiol | C7H7N3S | 详情 | 详情 | |
| (IX) | 12132 | 2,5-Dimethoxytetrahydrofuran; 5-Methoxytetrahydro-2-furanyl methyl ether | 696-59-3 | C6H12O3 | 详情 | 详情 |
| (X) | 20173 | 5-(1H-pyrrol-1-yl)-1H-benzimidazol-2-ylhydrosulfide; 5-(1H-pyrrol-1-yl)-1H-benzimidazole-2-thiol | C11H9N3S | 详情 | 详情 | |
| (XI) | 20174 | 2-[[(4-methoxy-3-methyl-2-pyridinyl)methyl]sulfanyl]-5-(1H-pyrrol-1-yl)-1H-benzimidazole; methyl 3-methyl-2-([[5-(1H-pyrrol-1-yl)-1H-benzimidazol-2-yl]sulfanyl]methyl)-4-pyridinyl ether | C19H18N4OS | 详情 | 详情 |