反应详情

To a solution of 3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxylic acid 3.6 g (20 mmol) of step 4 in dimethylformamide 50 mL were added 4-tert-butylbenzen-1,2-diamine 3.3 g (20 mmol), diisopropylethylamine 7 mL (40 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate 11 g (30 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, and dried over magnesium sulfate before being concentrated in a vacuum. The residue thus obtained was dissolved in acetic acid/toluene (45 mL/5 mL), stirred at 70° C. for 4 hrs, 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, and dried over magnesium sulfate before vacuum concentration. Purification by column chromatography (developing solvent: ethylacetate/hexane=1/1) gave 5.2 g of the title compound (yield 85%).

1. washwashed with a saturated sodium bicarbonate solution
2. dry with materiala saturated NaCl solution, and dried over magnesium sulfate
3. concentrationbefore being concentrated in a vacuum
4. customThe residue thus obtained
5. stirringstirred at 70° C. for 4 hrs
6. temperaturecooled to room temperature
7. concentrationconcentrated in a vacuum
8. dissolutionThe concentrate was dissolved in ethylacetate
9. washwashed with a saturated sodium bicarbonate solution
10. dry with materiala saturated NaCl solution, and dried over magnesium sulfate before vacuum concentration
11. customPurification by column chromatography (developing solvent: ethylacetate/hexane=1/1)