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合成 Cinnoxicam的制备有两条途径。 1.乙二醇(Ⅰ)以氯乙酰氯(Ⅱ)和三乙胺进行单乙酰化,得2-羟乙基氯乙酸酯(Ⅲ)。Ⅲ与糖精(Ⅳ)在乙二醇中经NaOH缩合,得2-羟乙基3-氧-1,2-苯并噻唑啉-2-醋酸酯-1,1-二氧化物(Ⅴ)。Ⅴ在二甲亚砜中经叔丁醇钾异构化,得2-羟乙基4-羟基-2 H-1,2-苯噻嗪-3-羧酸酯1,1-二氧化物(Ⅵ)。Ⅵ在碱性醇溶液中经碘甲烷甲基化,得到相应的N-甲基衍生物(Ⅶ),Ⅶ在碱性醇溶液中水解成相应的游离酸(Ⅷ)。Ⅷ与肉桂酰氯(Ⅸ)
There are two ways to synthesize Cinnoxicam. Ethylene glycol (I) is monoacetylated with chloroacetyl chloride (II) and triethylamine to give 2-hydroxyethyl chloroacetate (III). Ⅲ and saccharin (IV) are condensed in ethylene glycol by NaOH to give 2-hydroxyethyl 3-oxo-1,2-benzothiazoline-2-acetate-1,1-dioxide (V). V isomerised with potassium tert-butoxide in dimethylsulfoxide to give 2-hydroxyethyl 4-hydroxy-2H-1,2-phenothiazine-3-carboxylate 1,1-dioxide Ⅵ). Methyl iodide is methylated in a basic alcoholic solution to give the corresponding N-methyl derivative (VII) which is hydrolyzed in the basic alcoholic solution to the corresponding free acid (VIII). Ⅷ and cinnamoyl chloride (Ⅸ)