Methyl 4-hydroxy-2H-thieno[2,3-e]-1,2-thiazine-3-carboxylate-1,1-dioxide

Synthesis

General procedure for the synthesis of 4-hydroxy-2H-thieno[2,3-e]-1,2-thiazine-3-carboxylic acid methyl ester-1,1-dioxide from methyl 3-sulfonamidoacetate-2-thiophenecarboxylate: 8.5 g of methyl 3-sulfonamidoacetate-2-thiophenecarboxylic acid methyl ester (TNXK-1), 27.2 g of a 7% sodium methanol solution, and 15 mL of anhydrous methanol were mixed. The reaction was heated to reflux with stirring and maintained for 2 hours. After completion of the reaction, it was cooled to room temperature and the reaction mixture was diluted with 200 mL of water. Subsequently, the reaction mixture was neutralized with 10% hydrochloric acid solution to pH 3. After neutralization, the solvent was removed by evaporation, the residue was cooled, and the pH was adjusted again with 10% hydrochloric acid to 3. The precipitate was collected by filtration, and the filter cake was washed with water and dried to give 5.6 g of the yellowish-green solid product, 4-hydroxy-2H-thieno[2,3-e]-1,2-thiazine-3-carboxylic acid methyl ester-1,1 -dioxide (TNXK-2) The yield was 79%.

References

[1] Patent: CN107141308, 2017, A. Location in patent: Paragraph 0046-0050; 0064; 0068; 0074; 0078; 0084; 0088
[2] Journal of Medicinal Chemistry, 1987, vol. 30, # 4, p. 678 - 682