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【结 构 式】 
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【分子编号】56497 【品名】3-methoxy-2-methyl-1-pyridiniumolate 【CA登记号】 |
【 分 子 式 】C7H9NO2 【 分 子 量 】139.154 【元素组成】C 60.42% H 6.52% N 10.07% O 23% |
合成路线1
该中间体在本合成路线中的序号：(VIII)3-Methoxy-2-methylpyridine (VII), prepared by methylation of 2-methyl-3-pyridinol (VI), was converted to the N-oxide (VIII) employing peracetic acid. Nitration of the pyridine N-oxide (VIII) with concentrated nitric acid gave the 4-nitro derivative (IX). Subsequent displacement of the nitro group of (IX) by sodium methoxide led to the dimethoxypyridine N-oxide (X). Rearrangement of the N-oxide group of (X) in hot acetic anhydride produced the acetoxymethyl pyridine (XI). After basic hydrolysis of the acetate ester (XI), the resultant hydroxymethyl pyridine (XII) was chlorinated by SOCl2, yielding chloride (XIII). Condensation between mercapto benzimidazole (V) and the chloromethyl pyridine (XIII) in ethanolic NaOH led to the sulfide adduct (XIV). This was finally oxidized to the desired sulfoxide by using meta-chloroperbenzoic acid in CH2Cl2. The oxidation of sulfide (XIV) has also been performed employing sodium perborate, sodium percarbonate in the presence of ammonium molybdate, or tert-butyl hydroperoxide in the presence of vanadyl acetylacetonate.
| 【1】 Coppi, L.; Berenguer Maimó, R. (Laboratorios del Dr. Esteve, SA); Method for obtaining derivs. of [[pyridyl substd.)methyl]thio]benzimidazol. ES 2171116; WO 0179194 . |
| 【2】 Mendelovici, M.; Avrutov, I. (Teva Pharmaceutical Industries Ltd.; Teva Pharmaceuticals USA, Inc.); Processes for the production of substd. 2-(2-pyridylmethyl) sulfinyl-1H-benzimidazoles. WO 0262786 . |
| 【3】 Coppi, L.; Campon Pardo, J.; Berenguer Maimo, R. (Laboratorios del Dr. Esteve, SA); Method for oxidizing a thioether group into a sulfoxide group. ES 2163372; WO 0168594 . |
| 【4】 Brennan, J.P.; Turner, A.T. (Abbott Laboratories Inc.); Chemical process for the production of sulphinyl derivs. by oxidation of the corresponding co-derivs. with perborates. WO 9947514 . |
| 【5】 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 |
|---|---|---|---|---|---|---|
| (V) | 14034 | 5-(Difluoromethoxy)-1H-benzimidazole-2-thiol; 5-(Difluoromethoxy)-1H-benzimidazol-2-ylhydrosulfide; 5-Difluoromethoxy-2-mercapto-1H-benzimidazole | 97963-62-7 | C8H6F2N2OS | 详情 | 详情 |
| (VI) | 29609 | 2-methyl-3-pyridinol | 1121-25-1 | C6H7NO | 详情 | 详情 |
| (VII) | 56496 | 3-methoxy-2-methylpyridine; methyl 2-methyl-3-pyridinyl ether | C7H9NO | 详情 | 详情 | |
| (VIII) | 56497 | 3-methoxy-2-methyl-1-pyridiniumolate | C7H9NO2 | 详情 | 详情 | |
| (IX) | 56498 | 3-methoxy-2-methyl-4-nitro-1-pyridiniumolate | C7H8N2O4 | 详情 | 详情 | |
| (X) | 56499 | 3,4-dimethoxy-2-methyl-1-pyridiniumolate | C8H11NO3 | 详情 | 详情 | |
| (XI) | 56500 | (3,4-dimethoxy-2-pyridinyl)methyl acetate | C10H13NO4 | 详情 | 详情 | |
| (XII) | 56501 | (3,4-dimethoxy-2-pyridinyl)methanol | C8H11NO3 | 详情 | 详情 | |
| (XIII) | 14035 | 2-(Chloromethyl)-3,4-dimethoxypyridine; 2-(Chloromethyl)-3-methoxy-4-pyridinyl methyl ether | 72830-09-2 | C8H10ClNO2 | 详情 | 详情 |
| (XIV) | 14036 | 5-(Difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfanyl]-1H-benzimidazole; 2-([[5-(Difluoromethoxy)-1H-benzimidazol-2-yl]sulfanyl]methyl)-3-methoxy-4-pyridinyl methyl ether | 102625-64-9 | C16H15F2N3O3S | 详情 | 详情 |