药物详细合成路线
| Name | Metronidazole;IDR-90105(Ophthalmic);Rosased;Zidoval;Metrogel;Flagyl | | Chemical Name | 2-Methyl-5-nitro-1H-imidazole-1-ethanol | | CAS | 443-48-1 | | Related CAS | 133884-00-1 (deleted CAS) | | Formula | C6H9N3O3 | | Structure |  | | Formula Weight | 171.15693 | | Stage | 上市-1960 | | Company | Pfizer (Originator), 3M Pharmaceuticals (Not Determined), Novartis (Not Determined), Pierre Fabre (Not Determined), Institute for Drug Research (Licensee) | | Activity/Mechanism | Acne Therapy, Antiamebics, Antibacterial Drugs, Antibacterial Ophthalmic Drugs, Antifungal Agents, ANTIINFECTIVE THERAPY, Antitrichomonals, DERMATOLOGIC DRUGS, Ocular Antiinflammatory and Antiinfective Agents, OCULAR MEDICATIONS, Ophthalmic Drugs, Treatment of Protozoal Diseases | | Syn. Route | 6 | | Route 1 | | 2-methylimidazole (i) is converted into the bisulfate salt, and then nitrated by means of a sulfonitric mixture in ac2o to produce 2-methyl-4-nitroimidazole (ii) . in a variant of this procedure, 2-methylimidazole (i) is nitrated by using a ferric nitrate-tonsyl adduct in several solvents. imidazole (ii) is then regioselectively alkylated with boiling 2-chloroethanol to produce the title compound. alternatively, the alkylation of (ii) has been reported by treatment with ethylene oxide (iii) under acidic conditions. | | |  | | List of intermediates | No. | | 3-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-4-phenyl-1,4-dihydropyridine | (iii) | | (3ar,6as)-2-oxohexahydro-2h-cyclopenta[b]furan-4-carbaldehyde | (i) | | ethyl (1r,2s,4r)-2-isopropenyl-1-methyl-4-vinylcyclohexanecarboxylate | (ii) | | | Reference 1: frank, a.; karn, h.; spanig, h. (abbott gmbh & co. kg); production of 1-hydroxyalkyl-5-nitroimidazoles. de 2359625; fr 2253019; gb 1481349 . Reference 2: frank, a.; dockner, t.; karn, h. (abbott gmbh & co. kg); process for the preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole of high purity. ep 0150407 . |
Route 2 | | in an alternative procedure, the title compound is obtained by hydrolysis of the bromoethyl imidazole (i) in the presence of formic acid in aqueous formamide | | |  | | List of intermediates | No. | | | Reference 1: sunjic, v.; fajdiga, t.; kajfez, f.; process for preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole. de 1695321; gb 1138805; us 3520900 . |
Route 3 | | the title compound can be obtained by reaction of 1-(acetoxymethyl)-2-methyl-4-nitroimidazole (i) with ethylene oxide (ii) in the presence of sulfur trioxide, followed by hydrolysis in aqueous h2so4 | | |  | | List of intermediates | No. | | 3-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-4-phenyl-1,4-dihydropyridine | (ii) | | | Reference 1: lavigne, m.; mandard-cazin, b. (aventis pharma sa); process for preparing hydroxyalkyl-1 nitro-5 imidazoles. wo 9113877 . |
Route 4 | | in a related procedure, 1-(acetoxymethyl)-2-methyl-4-nitroimidazole (i) is condensed with ethyleneglycol diacetate (ii) in the presence of anhydrous h2so4, followed by hydrolysis or alcoholysis under acidic conditions to produce the title compound | | |  | | List of intermediates | No. | | | Reference 1: buforn, a.; massonneau, v.; mulhauser, m. (aventis sa); process for the preparation of 1-hydroxyalkyl-2-methyl-5-nitro-imidazoles. ep 0325513; fr 2625999 . |
Route 5 | | alternatively, 2-methyl-4-nitroimidazole (i) is protected by acylation in hot acetic anhydride to give (ii). addition of ethylene oxide (iii) to the n-acetyl imidazole (ii) in the presence of so3, followed by acidic hydrolysis furnishes the title compound | | |  | | List of intermediates | No. | | 3-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-4-phenyl-1,4-dihydropyridine | (iii) | | ethyl (1r,2s,4r)-2-isopropenyl-1-methyl-4-vinylcyclohexanecarboxylate | (i) | | | Reference 1: lavigne, m.; mandard-cazin, b. (aventis pharma sa); process for preparing hydroxyalkyl-1 nitro-5 imidazoles. wo 9113877 . |
Route 6 | | the title compound can also be obtained by alkylation, in different solvents, of 1-(acetoxymethyl)-2-methyl-4-nitroimidazole (i) with either ethylene sulfate (ii) or with bis-(2-acetoxyethyl) sulfate (iii) -generated from ethyleneglycol diacetate (iv) and either dimethyl sulfate or h2so4 - followed by hydrolysis or alcoholysis treatment | | |  | | List of intermediates | No. | | | Reference 1: massonneau, v.; mulhauser, m.; buforn, a. (aventis pharma sa); process for the preparation of hydroxyalkylating agents, the agents so prepared and their use. ep 0324692 . Reference 2: massonneau, v.; mulhauser, m.; buforn, a.; madard-cazin, b. (aventis pharma sa); process for the preparation of 1-hydroxyalkyl-5-nitro-imidazoles. ep 0324691 . |
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来源:药化网
作者:药化小编
摘要:本文合成路线介绍的是药物中文名甲硝唑；英文名Metronidazole;IDR-90105(Ophthalmic);Rosased;Zidoval;Metrogel;Flagyl；CAS[443-48-1]
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