反应详情

2-[2-(2,4-Difluoro-phenyl)-2H-[1,2,4]triazol-3-yl]-9-piperazin-1-yl-4,5-dihydro-6-oxa-1-thia-10-aza-benzo[e]azulene (150 mg, 0.32 mmol), HATU (244 mg, 0.64 mmol) and DIPEA (165 mg, 1.28 mmol) was dissolved in DMF (5 mL). The reaction mixture was stirred at room temperature for 2 hours. LC-MS showed the reaction is completed. To the reaction was added water (15 mL), some solid appeared. It was filtered, and the solid was collected and used to the next step directly (140 mg yield: 60%). The above residue (140 mg, 0.21 mmol) was dissolved in 5 mL of THF, and then NaOH (18 mg, 0.42 mmol) in 5 mL of water was added dropwise at 0° C. The reaction mixture was allowed to warm up to room temperature slowly and stirred at room temperature for 1 hour. Evaporated to remove most of THF, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated to dryness to afford 388 (45 mg, yield: 40%). 1H NMR (CDCl3, 400 MHz): δ8.08 (s, 1H), 7.54-7.51 (m, 1H), 7.24-7.02 (m, 4H), 6.54-6.53 (d, J=7.2 Hz, 1H), 4.55-4.51 (m, 1H), 4.24-4.22 (m, 2H), 3.82-3.76 (m, 3H), 3.52-3.50 (m, 4H), 3.43-3.41 (m, 2H), 3.11-3.08 (m, 2H), 1.40-1.38 (m, 6H). ESI-MS: m/z=539 [M+H+]

1. filtrationIt was filtered
2. customthe solid was collected
3. temperatureto warm up to room temperature slowly
4. stirringstirred at room temperature for 1 hour
5. customEvaporated
6. customto remove most of THF
7. extractionextracted with dichloromethane
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated to dryness