2-chloro-Thiazolo[4,5-b]pyridine

99158-61-9

152170-30-4

The general procedure for the synthesis of 2-chlorothiazolo[4,5-b]pyridine from thiazolo[4,5-b]pyridine-2(3H)-thione was as follows: sulfuryl chloride (3.32 mL, 40.8 mmol) was slowly added to a dichloromethane (0.5 mL) suspension of thiazolo[4,5-b]pyridine-2-thiol (343 mg, 2.039 mmol). The reaction mixture was stirred at 50 °C for 2 h, followed by continued stirring at room temperature overnight. Upon completion of the reaction, ice water was added to the yellow suspension and stirred at room temperature for 15 minutes to quench the excess sulfuryl chloride. Subsequently, the pH was adjusted to 10-12 by adding ethyl acetate (EtOAc) and 4.0 N sodium hydroxide (NaOH) solution.The organic layer was separated, washed with saturated brine and dried over anhydrous sodium sulfate. After concentration under reduced pressure to remove the solvent, the crude product was dissolved in a small amount of chloroform and purified by column chromatography on silica gel (12 g silica gel), eluting first with 5% eluent for 3 min and then using a 12% gradient elution (5% to 60%). The fractions containing the target product were combined and concentrated under reduced pressure to give Intermediate 9A (265 mg, 1.553 mmol, 76% yield) as a white solid. The structure of the product was confirmed by 1H NMR (500 MHz, chloroform-d): δ 8.76 (dd, J = 5.0, 1.7 Hz, 1H), 8.19 (dd, J = 8.0, 1.7 Hz, 1H), 7.39 (dd, J = 8.0, 4.7 Hz, 1H); LC-MS analysis (Method A): retention time (RT) = 1.22 min, mass spectrum (ESI) m/z: 171 and 173 ([M + H]+).