5-b]pyridine

1137089-65-6

1086423-62-2

The general procedure for the synthesis of 7-chloro-2-methyl-3H-imidazo[4,5-B]pyridine from the compound (CAS: 1137089-65-6) was as follows: intermediate 2A (12 g, 80 mmol) was dissolved in POCl3 (60.0 mL, 644 mmol) and gradually heated in an oil bath up to 80 °C, where slight bubbling was observed. After maintaining the reaction at this temperature for 15 min, the temperature was gradually increased to 120 °C. After reacting at 120 °C for 3 h, the reaction mixture was cooled to room temperature and the excess POCl3 was evaporated under reduced pressure to give an oily residue. This oily material was dissolved in dichloromethane (DCM, 50 mL), concentrated again and this operation was repeated to give a brown semi-solid. The semi-solid mixture was cooled in an ice bath and cold water (75 mL) was slowly added to form a clarified solution, which was subsequently transferred to a 1 L flask. Neutralization was carried out by adding saturated aqueous sodium bicarbonate solution dropwise under stirring conditions until the pH of the solution reached 7. After removing the ice bath, the mixture was continued to be stirred at room temperature for 30 min. Subsequent extraction with ethyl acetate (EtOAc, 200 mL x 4) was carried out and the organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated to give 124 g (92% yield) of a creamy white solid product, 7-chloro-2-methyl-3H-imidazo[4,5-B]pyridine. The product was characterized by 1H NMR (400 MHz, METHANOL-d4): δ 8.24 (d, J=4.0 Hz, 1H), 7.34 (d, J=5.3 Hz, 1H), 2.67 (s, 3H).