反应详情

To a solution of ethyl 1-(3-bromophenyl)-5-methyl-1H-pyrazole-3-carboxamide (from step 2 of EXAMPLE 1) (0.069 g, 0.24 mmol) in DMSO (1.14 mL), bis(pinacoloato)diboron (0.075 g, 0.3 mmol) was added followed by potassium acetate (0.072 g, 0.74 mmol) and PdCl2(dppf)2 (0.005 g, 3 mol %). The solution was heated in a Smith Creator™ microwave reactor (commercially available from Personal Chemistry, Inc.) at 140° C. for 1200 seconds. The reaction mixture was cooled to room temperature, and 2-bromo-5-fluorobenzotrifluoride (0.12 g, 0.5 mmol), PdCl2(dppf)2 (0.005 g, 3 mol %) and 2M sodium carbonate (0.61 mL, 1.2 mmol) were added to the reaction mixture. The reaction was then subjected to microwave radiation at 140° C. for 2800 seconds. After cooling to room temperature, the reaction mixture was partitioned between EtOAc and water. The organic layer was washed with saturated sodium bicarbonate and brine, then dried over sodium sulfate, filtered and concentrated. Purification of the crude product by reverse phase HPLC (acetonitrile/water system) (gradient: 45% to 100% acetonitrile over 10 minutes) yielded 0.036 mg of the product (41% yield, retention time 5.1 minutes).

1. temperatureThe solution was heated in a Smith Creator™ microwave reactor (commercially available from Personal Chemistry, Inc
2. customat 140° C.
3. customfor 2800 seconds
4. temperatureAfter cooling to room temperature
5. customthe reaction mixture was partitioned between EtOAc and water
6. washThe organic layer was washed with saturated sodium bicarbonate and brine
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification of the crude product by reverse phase HPLC (acetonitrile/water system) (gradient: 45% to 100% acetonitrile over 10 minutes)