【药物名称】Metronidazole, IDR-90105(Ophthalmic), Rosased, Zidoval, Metrogel, Flagyl
化学结构式(Chemical Structure):
参考文献No.10866
标题:Process for the preparation of 1-hydroxyalkyl-2-methyl-5-nitro-imidazoles
作者:Buforn, A.; Massonneau, V.; Mulhauser, M. (Aventis SA)
来源:EP 0325513; FR 2625999
合成路线图解说明:

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

参考文献No.62480
标题:Process for the preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole of high purity
作者:Frank, A.; Dockner, T.; Karn, H. (Abbott GmbH & Co. KG)
来源:EP 0150407
合成路线图解说明:

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.

参考文献No.62482
标题:Production of 1-hydroxyalkyl-5-nitroimidazoles
作者:Frank, A.; Karn, H.; Sp鋘ig, H. (Abbott GmbH & Co. KG)
来源:DE 2359625; FR 2253019; GB 1481349
合成路线图解说明:

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.

参考文献No.62483
标题:Process for preparation of 1-(2'-hydroxyethyl)-2-methyl-5-nitroimidazole
作者:Sunjic, V.; Fajdiga, T.; Kajfez, F.
来源:DE 1695321; GB 1138805; US 3520900
合成路线图解说明:

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

参考文献No.62484
标题:Process for preparing hydroxyalkyl-1 nitro-5 imidazoles
作者:Lavigne, M.; Mandard-Cazin, B. (Aventis Pharma SA)
来源:WO 9113877
合成路线图解说明:

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

合成路线图解说明:

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

参考文献No.62485
标题:Process for the preparation of 1-hydroxyalkyl-5-nitro-imidazoles
作者:Massonneau, V.; Mulhauser, M.; Buforn, A.; Madard-Cazin, B. (Aventis Pharma SA)
来源:EP 0324691
合成路线图解说明:

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

参考文献No.62486
标题:Process for the preparation of hydroxyalkylating agents, the agents so prepared and their use
作者:Massonneau, V.; Mulhauser, M.; Buforn, A. (Aventis Pharma SA)
来源:EP 0324692
合成路线图解说明:

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

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