반응 #674295
ord-a37fc8f051724aec9244c9a4b3868890
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후처리
- 1기타It was degassed again
- 2workup.ADDITIONrefilled with N2 (2 times)
- 3온도(heating bath) for 16 hrs
- 4온도The reaction mixture was cooled to room temperature
- 5workup.ADDITIONH2O (30 mL) was added
- 6추출The aqueous phase was extracted with EtOAc (30 mL) and DCM (3×30 mL)
- 7건조The combined organic phase was dried over anhydrous Na2SO4
- 8농축concentrated by evaporation in vacuo
- 9기타to give black residue which
- 10기타was purified by CombiFlash (40 g silica gel column, Hexane/EtOAc)
실험 절차
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.