Reacción #674295

Ecuación de reacción

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

Rendimiento 45.0%

Disolventes

DME

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente