- 【药物名称】Metronidazole, IDR-90105(Ophthalmic), Rosased, Zidoval, Metrogel, Flagyl
- 【化学名】2-Methyl-5-nitro-1H-imidazole-1-ethanol
- 【CAS登记号】443-48-1, 133884-00-1 (deleted CAS)
- 【结构式】
- 【分子式】C6-H9-N3-O3
- 【分子量】171.1551
- 【原研厂家】Pfizer (Originator), 3M Pharmaceuticals (Not Determined), Novartis (Not Determined), Pierre Fabre (Not Determined), Institute for Drug Research (Licensee)
- 【作用类别】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
- 【研发状态】Launched-1960
- 【合成情况】
- 〖来源〗EP 0150407
- 〖合成路线〗
- 〖标题〗Process for the preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole of high purity
- 〖合成方法〗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.
- 〖作者〗Frank, A.; Dockner, T.; Karn, H. (Abbott GmbH & Co. KG)
- 〖参考〗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
- 〖出处〗EP 0150407,,():
- 〖备注〗
- 〖来源〗DE 2359625; FR 2253019; GB 1481349
- 〖合成路线〗
- 〖标题〗Production of 1-hydroxyalkyl-5-nitroimidazoles
- 〖合成方法〗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.
- 〖作者〗Frank, A.; Karn, H.; Spnig, H. (Abbott GmbH & Co. KG)
- 〖参考〗Frank, A.; Karn, H.; Spnig, H. (Abbott GmbH & Co. KG); Production of 1-hydroxyalkyl-5-nitroimidazoles. DE 2359625; FR 2253019; GB 1481349
- 〖出处〗DE 2359625; FR 2253019; GB 1481349,,():
- 〖备注〗
- 〖来源〗DE 1695321; GB 1138805; US 3520900
- 〖合成路线〗
- 〖标题〗Process for preparation of 1-(2'-hydroxyethyl)-2-methyl-5-nitroimidazole
- 〖合成方法〗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
- 〖作者〗Sunjic, V.; Fajdiga, T.; Kajfez, F.
- 〖参考〗Sunjic, V.; Fajdiga, T.; Kajfez, F.; Process for preparation of 1-(2'-hydroxyethyl)-2-methyl-5-nitroimidazole. DE 1695321; GB 1138805; US 3520900
- 〖出处〗DE 1695321; GB 1138805; US 3520900,,():
- 〖备注〗
- 〖来源〗WO 9113877
- 〖合成路线〗
- 〖标题〗Process for preparing hydroxyalkyl-1 nitro-5 imidazoles
- 〖合成方法〗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
- 〖作者〗Lavigne, M.; Mandard-Cazin, B. (Aventis Pharma SA)
- 〖参考〗Lavigne, M.; Mandard-Cazin, B. (Aventis Pharma SA); Process for preparing hydroxyalkyl-1 nitro-5 imidazoles. WO 9113877
- 〖出处〗WO 9113877,,():
- 〖备注〗
- 〖来源〗EP 0325513; FR 2625999
- 〖合成路线〗
- 〖标题〗Process for the preparation of 1-hydroxyalkyl-2-methyl-5-nitro-imidazoles
- 〖合成方法〗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
- 〖作者〗Buforn, A.; Massonneau, V.; Mulhauser, M. (Aventis SA)
- 〖参考〗Buforn, A.; Massonneau, V.; Mulhauser, M. (Aventis SA); Process for the preparation of 1-hydroxyalkyl-2-methyl-5-nitro-imidazoles. EP 0325513; FR 2625999
- 〖出处〗EP 0325513; FR 2625999,,():
- 〖备注〗
- 〖来源〗WO 9113877
- 〖合成路线〗
- 〖标题〗Process for preparing hydroxyalkyl-1 nitro-5 imidazoles
- 〖合成方法〗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
- 〖作者〗Lavigne, M.; Mandard-Cazin, B. (Aventis Pharma SA)
- 〖参考〗Lavigne, M.; Mandard-Cazin, B. (Aventis Pharma SA); Process for preparing hydroxyalkyl-1 nitro-5 imidazoles. WO 9113877
- 〖出处〗WO 9113877,,():
- 〖备注〗
- 〖来源〗EP 0324691
- 〖合成路线〗
- 〖标题〗Process for the preparation of 1-hydroxyalkyl-5-nitro-imidazoles
- 〖合成方法〗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
- 〖作者〗Massonneau, V.; Mulhauser, M.; Buforn, A.; Madard-Cazin, B. (Aventis Pharma SA)
- 〖参考〗Massonneau, V.; Mulhauser, M.; Buforn, A.; Madard-Cazin, B. (Aventis Pharma SA); Process for the preparation of 1-hydroxyalkyl-5-nitro-imidazoles. EP 0324691
- 〖出处〗EP 0324691,,():
- 〖备注〗
- 〖来源〗EP 0324692
- 〖合成路线〗
- 〖标题〗Process for the preparation of hydroxyalkylating agents, the agents so prepared and their use
- 〖合成方法〗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
- 〖作者〗Massonneau, V.; Mulhauser, M.; Buforn, A. (Aventis Pharma SA)
- 〖参考〗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
- 〖出处〗EP 0324692,,():
- 〖备注〗
新药研发行业门户网站
制药行业专业信息平台
