Ethyl 4-chloro-5-methylthieno[2,3-d]pyrimidine-6-carboxylate

17417-67-3

101667-98-5

Ethyl 5-methyl-4-oxo-3,4-dihydrothieno[2,3-D]-pyrimidine-6-carboxylate (425 mg, 1.783 mmol) was used as a starting material, and after dissolution in toluene (8 mL), N,N-diisopropylethylamine (DIPEA, 248 μL, 1.426 mmol, 0.8 eq.) and phosphorus oxychloride (POCl3, 199 μ L, 2.14 mmol, 1.2 equiv). The reaction mixture was heated to reflux in an oil bath at 120-125°C for 3 hours. Upon completion of the reaction, the mixture was cooled to room temperature and subsequently slowly poured into a mixed system of ice-cooled saturated aqueous sodium bicarbonate (20 mL) and ethyl acetate (EtOAc, 50 mL) with rapid stirring to thoroughly quench the excess of phosphorous trichloride. The organic and aqueous phases were separated and the organic phase was washed once more with saturated aqueous sodium bicarbonate (20 mL). The organic layer was dried over anhydrous sodium sulfate (Na2SO4), filtered and concentrated under reduced pressure to afford ethyl 4-chloro-5-methylthieno[2,3-d]pyrimidine-6-carboxylate (25B) as a yellow solid (432 mg, 94% yield).