反应详情

To a solution of 5-(2-chloro-5-(3-fluoropyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylic acid (Example 105, 200 mg, 0.458 mmol), (1H-1,2,3-triazol-4-yl)methanamine (74 mg, 0.549 mmol) and N,N-diisopropylethylamine (406 μL, 2.29 mmol) in dichloromethane (3 mL) and N,N-dimethylformamide (1 mL) was added HATU (261 mg, 0.687 mmol). The reaction was stirred at room temperature for 2 hours. Further HATU (87 mg, 0.229 mmol) was added and the reaction continued for 3 hours. The reaction solution was partitioned between water (10 mL) and ethyl acetate (10 mL). The aqueous layer was further extracted with ethyl acetate (2×10 mL), and the combined organic layers were washed with brine (20 mL), dried over magnesium sulphate and concentrated in vacuo. The residue was purified by elution through an SCX-2 column using MeOH followed by 7N NH3 in MeOH followed by silica gel column chromatography eluting with 1% NH3(aq) and 8% MeOH in DCM to afford the title compound as white solid (51 mg, 21%).

1. waitthe reaction continued for 3 hours
2. customThe reaction solution was partitioned between water (10 mL) and ethyl acetate (10 mL)
3. extractionThe aqueous layer was further extracted with ethyl acetate (2×10 mL)
4. washthe combined organic layers were washed with brine (20 mL)
5. dry with materialdried over magnesium sulphate
6. concentrationconcentrated in vacuo
7. customThe residue was purified by elution through an SCX-2 column
8. washeluting with 1% NH3(aq) and 8% MeOH in DCM