反应详情

To a mixture of 5-tert-butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-ylamine (for reference procedure see for example WO2003072569, which is incorporated herein by reference in its entirety; 833 mg, 3.62 mmol) in NaOH (1M in water, 5.4 mL, 4.4 mmol) and EtOAc (5 mL) was added 2,2,2-trichloroethyl chloroformate (548 μL, 3.98 mmol) and the reaction mixture was stirred at RT for 1 h. Additional NaOH (1M in water, 5.4 mL) and 2,2,2-trichloroethyl chloroformate (548 μL) were added and stirring at RT was continued for 1 h. Additional NaOH (1M in water, 5.4 mL) and 2,2,2-trichloroethyl chloroformate (548 μL) were added and stirring at RT was continued for 2 h. Additional NaOH (1M in water, 10.8 mL) and 2,2,2-trichloroethyl chloroformate (1.10 mL) were added and stirring at RT was continued for 24 h. The aqueous layer was extracted with EtOAc (×3) and the combined organic layers were washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was purified by FCC on silica, using a gradient of 10-50% EtOAc in cyclohexane, to afford the title compound (550 mg, 37%) as a white foam. LCMS (Method 3): Rt 3.87 min, m/z 405 [MH+].

1. stirringstirring at RT
2. waitwas continued for 1 h
3. stirringstirring at RT
4. waitwas continued for 2 h
5. stirringstirring at RT
6. waitwas continued for 24 h
7. extractionThe aqueous layer was extracted with EtOAc (×3)
8. washthe combined organic layers were washed with brine
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated in vacuo
11. customThe resultant residue was purified by FCC on silica