反应详情

A mixture of 4-(2,6-difluorobenzylamino)-1H-pyrazole-3-carboxylic acid (100 mg, 0.37 mmol) (Example 16D), 6-chloro-pyridine-3,4-diamine (54 mg, 0.37 mmol), EDC (72 mg, 0.40 mmol), HOBt (57.3 mg, 0.40 mmol) and Et3N (0.075 ml, 0.55 mmol) in DMF (20 ml) was stirred at ambient temperature for 48 h and then partitioned between EtOAc and saturated aqueous sodium bicarbonate and the organic portion dried (MgSO4), filtered and evaporated. The amide intermediate was dissolved in AcOH (3 ml), heated at reflux for 1 h, and then heated in the microwave (150 W) at 160° C. until the reaction was complete. The reaction mixture was allowed to cool, a solid crystallised out, which was filtered and then washed with petroleum ether and dried to give the required product (9 mg). (LC/MS: Rt 2.74, [M+H]+ 375)

1. custompartitioned between EtOAc and saturated aqueous sodium bicarbonate
2. dry with materialthe organic portion dried (MgSO4)
3. filtrationfiltered
4. customevaporated
5. dissolutionThe amide intermediate was dissolved in AcOH (3 ml)
6. temperatureheated
7. temperatureat reflux for 1 h
8. temperatureheated in the microwave (150 W) at 160° C. until the reaction
9. temperatureto cool
10. customa solid crystallised out, which
11. filtrationwas filtered
12. washwashed with petroleum ether
13. customdried