反应详情

温度

80 °C

To a stirred solution of 4-((1,2,4)triazolo(1,5-a)pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazole-2-carbaldehyde (0.50 g, 1.64 mmol) in 1,2-dichloroethane (30 mL) were added 3-amino-4-((dimethylamino)methyl)benzonitrile (0.43 g, 2.46 mmol) and AcOH (0.20 g, 3.29 mmol), and the mixture was heated at 80° C. overnight. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in anhydrous MeOH (30 mL). To a methanolic solution at 0° C. was added NaBH4 (0.25 g, 6.57 mmol), and then the mixture was allowed to warm to room temperature and stirred for an additional 3 h. The pH of the reaction mixture was adjusted to 7-8 at 0° C. with 1 N HCl, and then MeOH was removed under reduced pressure. The aqueous mixture was extracted with CH2Cl2 (2×50 mL), and the CH2Cl2 solution was dried over anhydrous Na2SO4, filtered, and evaporated to dryness under reduced pressure. The residue was purified by MPLC on silica gel using a mixture of MeOH and CH2Cl2 (1:19 (v/v)) as eluent to give the titled compound (0.60 g, 79%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.99 (s, 1H), 8.36 (s, 1H), 7.86 (dd, 1H, J=9.2, 1.6 Hz), 7.78 (dd, 1H, J=9.2, 0.8 Hz), 7.47 (t, 1H, J=7.6 Hz), 7.23 (br d, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz), 7.01 (d, 1H, J=7.6 Hz), 6.98 (dd, 1H, J=7.6, 1.6 Hz), 6.93 (br s, 1H), 4.59 (s, 2H), 3.63 (s, 2H), 2.53 (s, 3H), 2.33 (s, 6H); MS (ESI) m/z 464.23 (MH+).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. dissolutionthe residue was dissolved in anhydrous MeOH (30 mL)
3. temperatureto warm to room temperature
4. customMeOH was removed under reduced pressure
5. extractionThe aqueous mixture was extracted with CH2Cl2 (2×50 mL)
6. dry with materialthe CH2Cl2 solution was dried over anhydrous Na2SO4
7. filtrationfiltered
8. customevaporated to dryness under reduced pressure
9. customThe residue was purified by MPLC on silica gel using
10. additiona mixture of MeOH and CH2Cl2 (1:19 (v/v)) as eluent