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【结 构 式】 
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【分子编号】50875 【品名】tert-butyl 2-(1,1,3-trioxo-1,3-dihydro-2H-1,2-benzisothiazol-2-yl)acetate 【CA登记号】 |
【 分 子 式 】C13H15NO5S 【 分 子 量 】297.33184 【元素组成】C 52.51% H 5.08% N 4.71% O 26.9% S 10.78% |
合成路线1
该中间体在本合成路线中的序号：(III)The condensation of sodium saccharin (I) with tert-butyl chloroacetate (II) in hot DMF gives the benzoisothiazolin-acetic ester (III), which is rearranged by means of potassium tert-butoxide in THF to yield 4-hydroxy-2H-1,2-benzothiazine-3-carboxylic acid tert-butyl ester 1,1-dioxide (IV). The methylation of (IV) with dimethyl sulfate and NaOH in water affords the 2-methyl derivative (V), which is acylated with cinnamoyl chloride (VI) and TEA in DMF to provide the 4-cinnamoyloxy derivative (VII). The cleavage of the tert-butyl group of (VII) by means of Tms-Cl, NaI and sodium thiosulfate gives the expected free acid (VIII), which is finally condensed with 2-aminopyridine (IX), previous activation with Cl2SO or ethyl chloroformate, and TEA in chloroform or dichloromethane to give rise to the target amide.
| 【1】 Montserrat Vidal, C.; Serra Masia, J. (Laboratorios Salvat SA); 4-Cinnamoyloxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide, process for obtaining it and intermediates for its preparation. ES 2053395 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 33704 | 1,1-Dioxide-1,2-benzisothiazol-3(2H)-one, sodium salt; 1,2-Benzisothiazol-3(2H)-one, 1,1-dioxide, sodium salt (1:1) | 38279-26-4 | C7H4NNaO3S | 详情 | 详情 |
| (II) | 40664 | tert-butyl 2-chloroacetate | 107-59-5 | C6H11ClO2 | 详情 | 详情 |
| (III) | 50875 | tert-butyl 2-(1,1,3-trioxo-1,3-dihydro-2H-1,2-benzisothiazol-2-yl)acetate | C13H15NO5S | 详情 | 详情 | |
| (IV) | 50876 | tert-butyl 4-hydroxy-1,1-dioxo-1,2-dihydro-1lambda(6),2-benzothiazine-3-carboxylate | C13H15NO5S | 详情 | 详情 | |
| (V) | 50877 | tert-butyl 4-hydroxy-2-methyl-1,1-dioxo-1,2-dihydro-1lambda(6),2-benzothiazine-3-carboxylate | C14H17NO5S | 详情 | 详情 | |
| (VI) | 11303 | (E)-3-Phenyl-2-propenoyl chloride; 3-Phenyl-2-propenoyl chloride | 102-92-1 | C9H7ClO | 详情 | 详情 |
| (VII) | 50878 | tert-butyl 2-methyl-1,1-dioxo-4-[[(E)-3-phenyl-2-propenoyl]oxy]-1,2-dihydro-1lambda(6),2-benzothiazine-3-carboxylate | C23H23NO6S | 详情 | 详情 | |
| (VIII) | 50879 | 2-methyl-1,1-dioxo-4-[[(E)-3-phenyl-2-propenoyl]oxy]-1,2-dihydro-1lambda(6),2-benzothiazine-3-carboxylic acid | C19H15NO6S | 详情 | 详情 | |
| (IX) | 11305 | 2-Pyridinamine; 2-Pyridinylamine; 2-Aminopyridine | 504-29-0 | C5H6N2 | 详情 | 详情 |