Reaktion #88905

Reaktionsgleichung

3-(tert-butyl)-1H-pyrazol-5-amine

5-bromo-2-fluorophenol

potassium carbonate

(1S,2S)—N,N′-bis-methyl-1,2-cyclohexane-diamine

→

title compound

Ausbeute 70.0%

5-(5-Amino-3-tert-butyl-pyrazol-1-yl)-2-fluoro-phenol

Ausbeute 70.0%

Lösungsmittel

EtOAc

water

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was degassed
2. 2
   Sonstigemicrowave irradiation
3. 3
   Temperaturthe reaction mixture heated at 150° C. for a further 1 h
4. 4
   Sonstigemicrowave irradiation
5. 5
   Sonstigethe phases separated
6. 6
   ExtraktionThe aqueous layer was then extracted with EtOAc (2×)
7. 7
   WaschenThe combined organic layers were washed with brine
8. 8
   Trocknendried (Na2SO4)
9. 9
   Filtrationfiltered
10. 10
    Sonstigeevaporated in vacuo
11. 11
    Sonstigeto give an impure solid
12. 12
    SonstigeThe residue was partitioned between DCM and water
13. 13
    Sonstigethe phases separated
14. 14
    SonstigeThe organic layer was evaporated in vacuo
15. 15
    Sonstigethe residue was purified by FCC
16. 16
    SonstigeFurther purification by FCC

Vorschrift

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+].

Quelle