反应详情

温度

80 °C

A mixture of 4-(5-Chloro-2-methoxy-benzoylamino)-1H-pyrazole-3-carboxylic acid (0.22 g, 0.745 mmol), 4-Methoxy-5-(4-methyl-piperidin-1-ylmethoxy)-benzene-1,2-diamine (0.2 g, 0.745 mmol), EDC (0.173 g, 0.89 mmol) and HOBt (0.122 g, 0.89 mmol) in DMF (20 ml) was stirred at 80° C. for 1 hour then at ambient temperature for 16 hours and then reduced in vacuo. The residue was partitioned between EtOAc and saturated bicarbonate, the organic portion was washed with brine and dried (MgSO4), filtered and evaporated. The amide intermediate (150 mg), (LC/MS (acidic method): Rt 2.13, [M+H]+ 543) was dissolved in AcOH (5 ml) then heated at reflux for 4 hours. The reaction mixture was allowed to cool, reduced in vacuo, residue purified by preparative TLC to yield 5-Chloro-2-methoxy-N-{3-[6-methoxy-5-(1-methyl-piperidin-4-ylmethoxy)-1H-benzimidazol-2-yl-]1H-pyrazol-4-yl}-benzamide (2 mg). (LC/MS (acidic method): Rt 2.25, [M+H]+ 525)

1. waitat ambient temperature for 16 hours
2. customThe residue was partitioned between EtOAc and saturated bicarbonate
3. washthe organic portion was washed with brine
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. customevaporated
7. dissolutionThe amide intermediate (150 mg), (LC/MS (acidic method): Rt 2.13, [M+H]+ 543) was dissolved in AcOH (5 ml)
8. temperaturethen heated
9. temperatureat reflux for 4 hours
10. temperatureto cool
11. custompurified by preparative TLC