Reaktion #86399

Reaktionsgleichung

(1R,5S)-3-(5-bromo-4-methylpyrimidin-2-yl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid

(6-(trifluoromethyl)-1H-indazol-4-yl)boronic acid

NaHCO3

(6-(trifluoromethyl)-1H-indazol-4-yl)boronic acid

→

title compound

(1R,5S)-3-(4-methyl-5-(6-(trifluoromethyl)-1H-indazol-4-yl)pyrimidin-2-yl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid

Lösungsmittel

dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeto give an orange suspension
2. 2
   SonstigeThe vial was sealed
3. 3
   Temperaturheating
4. 4
   SonstigeThe reaction mixture was subsequently partitioned between water (50 mL) and EtOAc (50 mL)
5. 5
   SonstigeThe phases were separated
6. 6
   Extraktionextracted with EtOAc (2×75 mL)
7. 7
   Waschenwashed with brine (50 mL)
8. 8
   Trocknendried over Na2SO4
9. 9
   Filtrationfiltered
10. 10
    Einengenconcentrated

Vorschrift

In a 10 mL microwave vial were mixed (1R,5S)-3-(5-bromo-4-methylpyrimidin-2-yl)-3-azabicyclo[3.1.0]hexane-2-carboxylic acid (200 mg, 0.671 mmol), (6-(trifluoromethyl)-1H-indazol-4-yl)boronic acid (201 mg, 0.872 mmol), PdCl2(dppf) (49.1 mg, 0.067 mmol), and aqueous NaHCO3 (1.435 mL, 2.68 mmol) in dioxane (10 mL) to give an orange suspension. The vial was sealed and heated in a microwave reactor to 140° C. for 40 minutes. Additional (6-(trifluoromethyl)-1H-indazol-4-yl)boronic acid (201 mg, 0.872 mmol) and PdCl2(dppf) (49.1 mg, 0.067 mmol) were added and heating was continued for 45 minutes. The reaction mixture was subsequently partitioned between water (50 mL) and EtOAc (50 mL). The phases were separated. The organic layer was discarded and the aqueous layer was acidified with 1N HCl and extracted with EtOAc (2×75 mL). The organic layers were combined, washed with brine (50 mL), dried over Na2SO4, filtered, and concentrated to give the title compound as a tan glass, which was used without further purification (170 mg, 62.8%).

Quelle