[Synthesis]
The general procedure for the synthesis of 4-chloro-2-methylthieno[2,3-D]pyrimidines from 4-hydroxy-2-methylthieno[2,3-D]pyrimidines was as follows: a few drops of pyridine were added to a solution of 2-methylthieno[2,3-d]pyrimidin-4(3H)-one (300 mg, 1.80 mmol) in phosphorus oxychloride (POCl3, 5.0 mL). The reaction mixture was heated to reflux for 24 hours. Upon completion of the reaction, the mixture was cooled to room temperature and slowly poured into ice water. Subsequently, saturated sodium carbonate (Na2CO3) solution was added to neutralize the excess trichlorophosphate. The aqueous phase was extracted with ethyl acetate (EtOAc) and the organic phase was combined. The organic phase was washed with saturated saline, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to remove the solvent. The crude product was purified by silica gel column chromatography with the eluent of petroleum ether/ethyl acetate (8:2, v/v) to afford the target compound 4-chloro-2-methylthieno[2,3-D]pyrimidine in 61% yield. The product was a yellow solid with a melting point of 93 °C. Nuclear magnetic resonance hydrogen spectrum (1H NMR, 200 MHz, CDCl3) δ= 7.48 (d, J = 6.0 Hz, 1H), 7.35 (d, J = 6.0 Hz, 1H), 2.79 (s, 3H). Nuclear magnetic resonance carbon spectrum (13C NMR, 50 MHz, CDCl3) δ= 169.2, 163.0, 154.4, 126.8, 126.6, 119.5, 25.5. liquid chromatography-mass spectrometry (LC-MS, ESI, 35 eV): retention time (tR) = 1.84 min, mass-to-charge ratio (m/z) = 185 [M + H]+ The results are summarized in the following table. |