Methyl 2-Amino-5-methylthiophene-3-carboxylate is used as a starting reagent in the synthesis of Thieno[2,3-b]Pyridinones and 4-Hydroxy-6-oxo-6,7-dihydro-thieno[2,3-b]pyridine derivatives, compounds that act as cytoprotectants and inhibitors of the N-Methyl-D-aspartate (NMDA) receptor.
1. Sulfur powder (960.0 mg, 30.0 mmol) and 5 mL of DMF were added to a single-necked vial and stirred until dissolved.
2. Methyl cyanoacetate (3.39 g, 30.0 mmol) and morpholine (1.48 g, 17.0 mmol) were added to the reaction vial sequentially, and the reaction solution gradually turned dark brown.
3. Propionaldehyde (1.74 g, 30.0 mmol) was added and the reaction mixture was stirred at 50 °C overnight.
4. After completion of the reaction, the mixture was cooled to room temperature and diluted with an appropriate amount of water.
5. The reaction mixture was extracted with ethyl acetate three times and the organic phases were combined. 6.
6. The combined organic phases were washed with water and then saturated brine. 7.
7. the organic phase was dried with anhydrous magnesium sulfate, filtered and distilled under reduced pressure to remove the solvent, the crude product was obtained.
8. The crude product was separated and purified by column chromatography to obtain the yellowish solid product methyl 2-amino-5-methylthiophene-3-carboxylate.
Yield: 73.6%.
[1] Patent: CN106167497, 2016, A. Location in patent: Paragraph 0241; 0242; 0243
[2] ChemMedChem, 2018,
[3] European Journal of Medicinal Chemistry, 2017, vol. 132, p. 219 - 235
[4] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 2, p. 305 - 308
[5] Patent: WO2013/190137, 2013, A2. Location in patent: Page/Page column 73
