反应详情

温度

150 °C

To a solution of 1-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)-piperidine-4-carboxylic acid (compound 26, 50 mg, 0.15 mmol) and 2,3-diaminopyridine (33 mg, 0.30 mmol) in CH2Cl2 (0.5 mL) is added polyphosphoric acid (1 mL). The mixture is concentrated to remove CH2Cl2. After being stirred at 150° C. for 1.5 h, the mixture is cooled to 25° C., diluted with water (10 mL), and basified by 10% aqueous solution of sodium hydroxide to pH˜8. The aqueous solution is extracted with CH2Cl2 (5×15 mL). The combined organic layers are concentrated and purified by HPLC (CH3CN/H2O: 22% 45% with 0.1% TFA) to give 2-[1-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)-piperidin-4-yl]-1H-imidazo[4,5-b]pyridine (33.8 mg, 55%).

1. concentrationThe mixture is concentrated
2. customto remove CH2Cl2
3. temperaturethe mixture is cooled to 25° C.
4. additiondiluted with water (10 mL)
5. extractionThe aqueous solution is extracted with CH2Cl2 (5×15 mL)
6. concentrationThe combined organic layers are concentrated
7. custompurified by HPLC (CH3CN/H2O: 22% 45% with 0.1% TFA)