反应详情

To a solution of (S)-3-(hydroxymethyl)-4-(5-methoxypyridin-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxylic acid 3.2 g (10 mmol) of step 7 in dimethylformamide 50 mL were 4-(trifluoromethyl)benzen-1,2-diamine 1.9 g (11 mmol), diisopropylethylamine 3.5 mL (20 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate 5.7 g (15 mmol), followed by stirring at room temperature for 3 hrs. The reaction mixture was diluted with ethylacetate, washed with a saturated sodium bicarbonate solution and a saturated NaCl solution, dried over magnesium sulfate and concentrated in a vacuum. The concentrate was dissolved in acetic acid/toluene (90 mL/10 mL), heated at 75° C. for 4 hrs with stirring, cooled to room temperature and concentrated in a vacuum. The concentrate was dissolved in ethylacetate, washed with a saturated sodium bicarbonate solution and a saturated NaCl solution, dried over magnesium sulfate, and concentrated under reduced pressure. Purification by column chromatography (developing solvent: ethylacetate/hexane=2/3) afforded 4.1 g of the title compound (yield 82%).

1. washwashed with a saturated sodium bicarbonate solution
2. dry with materiala saturated NaCl solution, dried over magnesium sulfate
3. concentrationconcentrated in a vacuum
4. dissolutionThe concentrate was dissolved in acetic acid/toluene (90 mL/10 mL)
5. temperatureheated at 75° C. for 4 hrs
6. stirringwith stirring
7. temperaturecooled to room temperature
8. concentrationconcentrated in a vacuum
9. dissolutionThe concentrate was dissolved in ethylacetate
10. washwashed with a saturated sodium bicarbonate solution
11. dry with materiala saturated NaCl solution, dried over magnesium sulfate
12. concentrationconcentrated under reduced pressure
13. customPurification by column chromatography (developing solvent: ethylacetate/hexane=2/3)