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【结 构 式】 
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【分子编号】14033 【品名】4-(Difluoromethoxy)-1,2-benzenediamine; 2-Amino-4-(difluoromethoxy)phenylamine 【CA登记号】 |
【 分 子 式 】C7H8F2N2O 【 分 子 量 】174.1502064 【元素组成】C 48.28% H 4.63% F 21.82% N 16.09% O 9.19% |
合成路线1
该中间体在本合成路线中的序号：(II)A new synthesis of [14C]-labeled pantoprazole has been described: The cyclization of potassium [14C]-ethylxanthate (I) with the diaminobenzene (II) by means of NaOH gives the imidazole (III), which is condensed with 2-(chloromethyl)-3,4-dimethoxypyridine (IV) by means of NaOH in ethanol to afford the sulfide (V). Finally, this compound is oxidized with m-chloroperbenzoic acid (mcpba) in dichloromethane.
| 【1】 Saunders, D.; Lawrie, K.W.M.; Crowe, A.M.; Johnston, C.E.A.; The synthesis of [14C]pantoprazole - SK&F 96022Z - An H+/K+ ATP inhibitor. J Label Compd Radiopharm 1992, 31, 5, 409. |
| 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) | 14032 | Dithiocarbonic acid O-ethyl ester potassium salt | C3H5KOS2 | 详情 | 详情 | |
| (I) | 45190 | potassium 1-(carbodithioatooxy)ethane | C3H5KOS2 | 详情 | 详情 | |
| (II) | 14033 | 4-(Difluoromethoxy)-1,2-benzenediamine; 2-Amino-4-(difluoromethoxy)phenylamine | C7H8F2N2O | 详情 | 详情 | |
| (III) | 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 |
| (III) | 45191 | 5-(difluoromethoxy)-1H-benzimidazole-2-thiol; 5-(difluoromethoxy)-1H-benzimidazol-2-ylhydrosulfide | C8H6F2N2OS | 详情 | 详情 | |
| (IV) | 14035 | 2-(Chloromethyl)-3,4-dimethoxypyridine; 2-(Chloromethyl)-3-methoxy-4-pyridinyl methyl ether | 72830-09-2 | C8H10ClNO2 | 详情 | 详情 |
| (V) | 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 |
| (V) | 45192 | 2-([[5-(difluoromethoxy)-1H-benzimidazol-2-yl]sulfanyl]methyl)-3-methoxy-4-pyridinyl methyl ether; 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl]sulfanyl]-1H-benzimidazole | C16H15F2N3O3S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The precursor 5-(difluoromethoxy)-2-mercaptobenzimidazole (V) was prepared by the following route. Nitration of N-(p-difluoromethoxyphenyl)acetamide (I) provided nitro anilide (II), which was hydrolyzed to the corresponding nitro aniline (III) employing methanolic NaOMe. Reduction of (III) to the phenylenediamine (IV) was performed by catalytic hydrogenation over Pd/C. Then, cyclization of diamine (IV) with potassium O-ethyl dithiocarbonate gave rise to the benzimidazole (V).
| 【1】 Kohl, B.; Sturm, E.; Klemm, K.; Riedel, R.; Figala, V.; Rainer, G.; Schaefer, H.; Senn-Bilfinger, J. (Altana Pharma Deutschland GmbH ); Dialkoxypyridines, process for their preparation, their use and medicines containing them. AU 8543640; EP 0166287; JP 1986022079; US 4758579 . |
| 【2】 Rainer, G.; Riedel, R.; Senn-Bilfinger, J.; Klemm, K.; Schaefer, H.; Figala, V. (Altana Pharma Deutschland GmbH ); Antisecretory substd. pyridylmethylthio-(or sulfinyl)benzimidazoles. EP 0134400; JP 1984206379; JP 1993086037; US 4555518 . |
| 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) | 56493 | N-[4-(difluoromethoxy)phenyl]acetamide | C9H9F2NO2 | 详情 | 详情 | |
| (II) | 56494 | N-[4-(difluoromethoxy)-2-nitrophenyl]acetamide | C9H8F2N2O4 | 详情 | 详情 | |
| (III) | 56495 | 4-(difluoromethoxy)-2-nitroaniline; 4-(difluoromethoxy)-2-nitrophenylamine | C7H6F2N2O3 | 详情 | 详情 | |
| (IV) | 14033 | 4-(Difluoromethoxy)-1,2-benzenediamine; 2-Amino-4-(difluoromethoxy)phenylamine | C7H8F2N2O | 详情 | 详情 | |
| (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 |