反应详情

温度

150 °C

To a solution of 3-(tert-butyl)-1H-pyrazol-5-amine (1.00 g, 7.20 mmol) in toluene (13 mL) was added 5-bromo-2-fluorophenol (1.51 g, 7.90 mmol), potassium carbonate (2.08 g, 15.1 mmol), (1S,2S)—N,N′-bis-methyl-1,2-cyclohexane-diamine (0.20 g, 1.40 mmol) then copper (I) iodide (0.07 g, 0.36 mmol). The mixture was degassed then heated at 150° C. for 1 h using microwave irradiation. Another portion of copper (I) iodide (0.07 g, 0.36 mmol) was added and the reaction mixture heated at 150° C. for a further 1 h using microwave irradiation. The mixture was diluted with EtOAc and water and the phases separated. The aqueous layer was then extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo to give an impure solid. The residue was partitioned between DCM and water and the phases separated. The organic layer was evaporated in vacuo and the residue was purified by FCC, using 0-5% MeOH in DCM. Further purification by FCC, using 0-25% EtOAc in DCM, gave the title compound as an orange gum (1.25 g, 70%). LCMS (Method 3): Rt 2.33 min, m/z 250.3 [MH+].

1. customThe mixture was degassed
2. custommicrowave irradiation
3. temperaturethe reaction mixture heated at 150° C. for a further 1 h
4. custommicrowave irradiation
5. customthe phases separated
6. extractionThe aqueous layer was then extracted with EtOAc (2×)
7. washThe combined organic layers were washed with brine
8. dry with materialdried (Na2SO4)
9. filtrationfiltered
10. customevaporated in vacuo
11. customto give an impure solid
12. customThe residue was partitioned between DCM and water
13. customthe phases separated
14. customThe organic layer was evaporated in vacuo
15. customthe residue was purified by FCC
16. customFurther purification by FCC