反应详情

To a solution of 6-bromo-N-(5-(5-(hydroxymethyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (142) (200 mg, 0.47 mmol) and DIEA (0.25 mL, 1.41 mmol) in dichloromethane (5 mL) was added MsCl (108.1 mg, 0.94 mmol). The mixture was stirred at room temperature for 10 minutes and then diluted with dichloromethane (10 mL) and washed with water. The organic layers were dried over Na2SO4, filtered and concentrated to give a residue which was dissolved in DMF (2 mL). Then azetidine-3-carbonitrile (116 mg, 1.41 mmol) was added and the reaction mixture was heated at 80° C. for 1 hour. The reaction mixture was diluted with water (50 mL) and extracted with EtOAc. The organic layers were dried over Na2SO4, filtered and concentrated to give the crude product which was purified by silica chromatography to yield 6-bromo-N-(5-(5-((3-cyanoazetidin-1-yl)methyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (143). 1H NMR (400 MHz, d6-DMSO) δ 10.15 (s, 1H), 9.62 (dd, J=0.8, 2.0 Hz, 1H), 8.60 (s, 1H), 8.07 (d, J=1.6 Hz, 1H), 7.83 (dd, J=1.6, 8.0 Hz, 1H), 7.79 (dd, J=0.8, 9.6 Hz, 1H), 7.68 (dd, J=2.0, 9.6 Hz, 1H), 7.51 (d, J=8.4 Hz, 1H), 4.06 (s, 2H), 3.67 (m, 2H), 3.51-3.60 (m, 3H), 2.37 (s, 3H). MS m/z 492.0, 494.0 (M+1)+.

1. washwashed with water
2. dry with materialThe organic layers were dried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated
5. customto give a residue which
6. temperaturethe reaction mixture was heated at 80° C. for 1 hour
7. extractionextracted with EtOAc
8. dry with materialThe organic layers were dried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto give the crude product which
12. customwas purified by silica chromatography