反应详情

To a solution of 4-(5-chloropyridin-3-yl)-2-[(2S)-2-(fluoromethyl)pyrrolidi n-1-yl]-N′-hydroxy-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carboximidamide (408 mg, 0.82 mmol) and 1,1′-carbonyldiimidazole (146 mg, 0.90 mmol) dissolved in acetonitrile (8.2 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.488 mL, 3.26 mmol). The reaction mixture was stirred at room temperature for 1 hour. The reaction was washed with water and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to afford 3-{4-(5-chloropyridin-3-yl)-2-[(2S)-2-(fluoromethyl)pyrrolidin-1-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one. MS ESI calc'd. for C26H29ClFN7O2 [M+H]+ 526. found 526. 1H NMR (500 MHz, DMSO-d6) δ 12.83 (s, 1H), 8.93 (s, 1H), 8.78 (s, 1H), 8.48 (s, 1H), 7.83 (s, 1H), 4.67-4.42 (m, 3H), 3.91-3.81 (m, 1H), 3.79-3.64 (m, 2H), 3.53-3.45 (m, 1H), 2.20-2.12 (broad, 1H), 2.06-1.98 (broad, 1H), 1.94-1.78 (m, 2H), 1.40-1.31 (broad, 2H), 1.17-1.07 (broad, 1H), 1.06-0.96 (broad, 1H), 0.89 (d, J=12.5, 1H), 0.67 (d, J=6.4, 3H), 0.63-0.36 (m, 5H).

1. washThe reaction was washed with water
2. extractionextracted with dichloromethane
3. dry with materialThe organic layer was dried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)