反应详情

A mixture of 6-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}pyridazine-3-carboxylic acid (150 mg, 0.4 mmol), DPPA (100 μL, 0.46 mmol) and Et3N (65 μL, 0.46 mmol) in DMF (1.5 mL) was stirred at r.t. overnight. MeOH (150 μL, 3.7 mmol) was then added and the mixture was heated at 65-70° C. for 6 h. After cooling, the mixture was diluted with water and extracted with EtOAc. The EtOAc extract was washed twice with water, dried (Na2SO4) and concentrated. CombiFlash chromatography (10 g, 40-80% EtOAc in hexanes in 20 min, 20 mL/min, 15 mL/fraction) gave the title compound as a white solid. 1H NMR (500 MHz, acetone-d6): δ 1.89-1.97 (m, 2H), 2.15 (m, 2H), 3.65-3.71 (m, 2H), 3.76 (s, 3H), 3.87-3.93 (m, 2H), 4.94-4.98 (m, 1H), 7.11 (t, 1H), 7.37 (m, 2H), 7.61-7.67 (m, 2H), 8.00 (d, 1H), 9.11 (s, 1H). MS (+ESI) m/z 397 (MH+).

1. temperaturethe mixture was heated at 65-70° C. for 6 h
2. temperatureAfter cooling
3. extractionextracted with EtOAc
4. extractionThe EtOAc extract
5. washwas washed twice with water
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated