反应 #674295

反应方程式

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

收率 45.0%

溶剂

DME

反应条件

后处理

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

实验过程

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.

来源