反应详情

A mixture of 4-(2,6-difluorobenzylamino)-1H-pyrazole-3-carboxylic acid (690 mg, 2.6 mmol) Example 16D), methyl 2,3-diaminobenzoate (415 mg, 2.6 mmol), EDC (590 mg, 3.1 mmol) and HOBt (415 mg, 3.1 mmol) in DMF (10 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, reduced then crystallised from hot EtOH. The amide intermediate (480 mg) was dissolved in AcOH (10 ml) then heated at reflux for 3 h. The reaction mixture was reduced in vacuo and then azeotroped with toluene (2×20 ml) to afford 2-[4-(2,6-difluoro-benzoylamino)-1H-pyrazol-3-yl]-1H-benzimidazole-4-carboxylic acid methyl ester (420 mg) as a fawn coloured solid. (LC/MS: Rt 3.82, [M+H]+ 398).

1. customThe residue was partitioned between EtOAc and brine
2. dry with materialthe organic portion dried (MgSO4)
3. filtrationfiltered
4. customreduced then crystallised from hot EtOH
5. dissolutionThe amide intermediate (480 mg) was dissolved in AcOH (10 ml)
6. temperaturethen heated
7. temperatureat reflux for 3 h
8. customazeotroped with toluene (2×20 ml)