发明授权
US4477661A Process for the preparation of
4-hydroxy-3-(heterocyclocarbamoyl)-2H-1,2-benzothiazine-1,1-dioxides
失效
制备4-羟基-3-(杂环氨基甲酰基)-2H-1,2-苯并噻嗪-1,1-二氧化物的方法
- 专利标题: Process for the preparation of 4-hydroxy-3-(heterocyclocarbamoyl)-2H-1,2-benzothiazine-1,1-dioxides
- 专利标题(中): 制备4-羟基-3-(杂环氨基甲酰基)-2H-1,2-苯并噻嗪-1,1-二氧化物的方法
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申请号: US478763申请日: 1983-03-25
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公开(公告)号: US4477661A公开(公告)日: 1984-10-16
- 发明人: Wolfgang Herrmann , Wolfram Geibel , Gerhard Satzinger
- 申请人: Wolfgang Herrmann , Wolfram Geibel , Gerhard Satzinger
- 申请人地址: NJ Morris Plains
- 专利权人: Warner-Lambert Company
- 当前专利权人: Warner-Lambert Company
- 当前专利权人地址: NJ Morris Plains
- 优先权: DEX3212485 19820403
- 主分类号: C07D417/12
- IPC分类号: C07D417/12 ; C07D401/12
摘要:
The present invention provides a process for the preparation of 4-hydroxy-3-(heterocyclocarbamoyl)-2H-1,2-benzothiazine-1,1-dioxides of the general formula: ##STR1## wherein R.sub.1 is a hydrogen atom or a methyl radical, R.sub.2 is a nitrogen-containing heterocyclic radical and R.sub.3 is a hydrogen or halogen atom or a methyl radical, and of the alkali metal, alkaline earth metal and amine salts thereof, by the reaction of an amine-substituted, nitrogen-containing heterocyclic compound with a halo-acetyl halide, reaction of the intermediate thus obtained with sodium benzoic acid sulphimide, ring expansion of the benzoisothiazole ring to give a benzothiazine ring and, in case R.sub.2 is to be an isoxazolyl radical, reverse rearrangement of the oxadiazole-ring formed by ring expansion to the isoxazolyl ring, wherein (in a one-pot reaction A) the reaction of an amine-substituted, nitrogen-containing heterocyclic compound with a halo-acetyl halide is carried out, without the addition of a base, in boiling ethyl acetate, the intermediate formed is, without isolation, reacted with sodium benzoic acid sulphimide and the reaction product isolated, whereafter, in a one-pot reaction B, the reaction product from the one-pot reaction A is reacted in a dipolar aprotonic solvent under an atmosphere of a protection gas with a strongly basic alkali-alkohole and thereafter with so much acid that about 2 equivalents of base remained unneutralized in the reaction solution and, if desired, the benzothiazine ring is N-methylated in the usual manner and the product obtained is, if desired, converted in known manner into an alkali metal, alkaline earth metal or amine salt.
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