Reaktion #88954

Reaktionsgleichung

potassium carbonate

trans-N,N′-Dimethyl-1,2-cyclohexanediamine

Intermediate 74d

{4-Iodo-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazol-3-yl}-methanol

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

→

title compound

Ausbeute 63.0%

{5-Amino-3-tert-butyl-1′-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1′H-[1,4′]bipyrazolyl-3′-yl}-methanol

Ausbeute 63.0%

Lösungsmittel

water

ammonium hydroxide

EtOAc

xylene

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was degassed
2. 2
   Sonstigemicrowave irradiation
3. 3
   Temperaturthe reaction mixture heated at 150° C. for a further 2 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 water and brine
8. 8
   Trocknendried (Na2SO4)
9. 9
   Filtrationfiltered
10. 10
    Sonstigeevaporated in vacuo
11. 11
    SonstigeThe residue was purified by FCC

Vorschrift

A solution of Intermediate 74d (0.51 g, 1.45 mmol) in xylene (2.4 mL) was treated with 3-(tert-butyl)-1H-pyrazol-5-amine (0.18 g, 1.32 mmol) then potassium carbonate (0.38 g, 2.76 mmol), trans-N,N′-Dimethyl-1,2-cyclohexanediamine (0.037 g, 0.26 mmol) and copper (I) iodide (0.013 g, 0.066 mmol) were added. The mixture was degassed then heated at 150° C. for 4 h using microwave irradiation. Another portion of copper (I) iodide (0.006 g, 0.03 mmol) was added and the reaction mixture heated at 150° C. for a further 2 h using microwave irradiation. The mixture was diluted with water (1 mL), conc. aqueous ammonium hydroxide (1 mL) and EtOAc (1 mL) and the phases separated. The aqueous layer was then extracted with EtOAc (2×). The combined organic layers were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by FCC, using 0-5% MeOH in DCM to give the title compound as a dark green gum (0.30 g, 63%). LCMS (Method 3): Rt 2.46 min, m/z 364 [MH+].

Quelle