反应详情

A mixture of 4-(2,6-difluorobenzylamino)-1H-pyrazole-3-carboxylic acid (520 mg, 1.96 mmol) (Example 16D), 3-bromo-5-trifluoromethyl-1,2-benzenediamine (500 mg, 1.96 mmol), EDC (413 mg, 2.15 mmol) and HOBt (290 mg, 2.15 mmol) in DMF (20 ml) was stirred at ambient temperature for 16 h and then reduced in vacuo. The residue was partitioned between EtOAc and brine and the organic portion dried (MgSO4), filtered and evaporated. The amide intermediate was chromatographed using EtOAc-P.E. (1:4-1:0). The intermediate amide (271 mg), (LC/MS: Rt 3.31, [M+H]+ 505), was dissolved in AcOH (3 ml) then heated at reflux for 1 h. The reaction mixture was allowed to cool at which time a solid crystallised out, that was filtered, washed with P.E. and dried to give the title compound (50 mg). (LC/MS: Rt 3.42, [M+H]+ 486,488)

1. customThe residue was partitioned between EtOAc and brine
2. dry with materialthe organic portion dried (MgSO4)
3. filtrationfiltered
4. customevaporated
5. customThe amide intermediate was chromatographed
6. dissolutionThe intermediate amide (271 mg), (LC/MS: Rt 3.31, [M+H]+ 505), was dissolved in AcOH (3 ml)
7. temperaturethen heated
8. temperatureat reflux for 1 h
9. temperatureto cool at which time a solid
10. customcrystallised out,
11. filtrationthat was filtered
12. washwashed with P.E
13. customand dried