955979-15-4

885618-31-5

955979-15-4

Under nitrogen protection, 2-chloro-4-(4-morpholinato)-thieno[3,2-d]pyrimidine-6-carboxaldehyde (20.0 g, 70.4 mmol, 1.0 eq.) was dissolved in methanol (125 mL) followed by addition of methylamine solution (27% v/v, 75 mL, 563.2 mmol). The reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure to give the crude product. The crude product was dissolved in methanol (550 mL) and tetrahydrofuran (220 mL) under nitrogen protection, and sodium borohydride (8 g, 211.2 mmol) was added in batches. The reaction mixture was stirred overnight at room temperature and concentrated under reduced pressure. Water (300 mL) was added to the concentrate and the aqueous phase was extracted with dichloromethane. The organic phases were combined, dried over anhydrous sodium sulfate and concentrated. The residue was dissolved in 6 M hydrochloric acid (230 mL) and stirred for 30 minutes. The aqueous phase was washed several times with dichloromethane and the pH was subsequently adjusted to 9-10 with 4N sodium hydroxide solution. the precipitated solid was collected by filtration and dried at 60 °C for 6 h to give a light yellow solid product (18 g, 85% yield). Melting point: 240-245°C. LCMS (m/z): 299 [M + 1]+. 1H NMR (400MHz, DMSO-d6): δ 2.32 (s, 3H), 3.74 (t, J=5.2Hz, 4H), 3.88 (t, J=5.2Hz, 4H), 3.96 (s, 2H), 7.24 (s, 1H).