Reaktion #674295

Reaktionsgleichung

Na2CO3

N2

tert-Butyl 6-(4-bromo-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate

(±)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine

N2

→

(±)-tert-butyl 6-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate

Ausbeute 45.0%

Lösungsmittel

DME

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeIt was degassed again
2. 2
   workup.ADDITIONrefilled with N2 (2 times)
3. 3
   Temperatur(heating bath) for 16 hrs
4. 4
   TemperaturThe reaction mixture was cooled to room temperature
5. 5
   workup.ADDITIONH2O (30 mL) was added
6. 6
   ExtraktionThe aqueous phase was extracted with EtOAc (30 mL) and DCM (3×30 mL)
7. 7
   TrocknenThe combined organic phase was dried over anhydrous Na2SO4
8. 8
   Einengenconcentrated by evaporation in vacuo
9. 9
   Sonstigeto give black residue which
10. 10
    Sonstigewas purified by CombiFlash (40 g silica gel column, Hexane/EtOAc)

Vorschrift

tert-Butyl 6-(4-bromo-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (145 mg, 0.42 mmol) and (±)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (268 mg, 0.63 mmol) were added to a round bottom flask. It was vacuumed and refilled with N2 (3 times). DME (2.0 mL) and a solution of Na2CO3 (2.0 M, 1.0 mL) were sequentially added. It was vacuumed and refilled with N2 (3 times). Pd(PPh3)2Cl2 (14.7 mg, 0.021 mmol) was added. It was degassed again refilled with N2 (2 times). The mixture was stirred at 90° C. (heating bath) for 16 hrs. The reaction mixture was cooled to room temperature and H2O (30 mL) was added. The aqueous phase was extracted with EtOAc (30 mL) and DCM (3×30 mL). The combined organic phase was dried over anhydrous Na2SO4, concentrated by evaporation in vacuo to give black residue which was purified by CombiFlash (40 g silica gel column, Hexane/EtOAc) to afford (±)-tert-butyl 6-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-2-azaspiro[3.3]heptane-2-carboxylate (106 mg, 45%) as a off-white solid.

Quelle