General procedure for the synthesis of 6-bromo-4-chlorothieno[3,2-d]pyrimidines from 4-chlorothieno[3,2-d]pyrimidines: to dry 200 mL of tetrahydrofuran was added lithium diisopropylamine (25 mL, 61.54 mmol), and the reaction system was cooled to -78 °C. Subsequently, 4-chlorothieno[3,2-d] Pyrimidine (5 g, 39.30 mmol) was slowly added dropwise to the above mixture. After 20 min of reaction, 1,2-dibromo-1,1,2,2-tetrafluoroethane (11.45 g, 35.17 mmol) was slowly added. Stirring was continued at -78°C for 20 minutes, then gradually warmed to room temperature and continued for 2 hours. Upon completion of the reaction, water was added to the mixture and extracted with chloroform (3 x 300 mL), the organic phases were combined and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, the mixture was developed with 200 mL of hexane to afford 6-bromo-4-chlorothieno[3,2-d]pyrimidine (6.5 g, 89.2% yield) as a dark brown solid. The product was characterized by 1H-NMR (400 MHz, CDCl3): δ 8.94 (s, 1H), 7.62 (s, 1H); LC-MS showed molecular ion peaks of 249 and 251 (MH+).
![4-Chlorothieno[3,2-d]pyrimidine](/CAS/GIF/16269-66-2.gif)
![6-bromo-4-chlorothieno[3,2-d]pyrimidine](/CAS/GIF/225385-03-5.gif)