反应 #674302
ord-92bcbbf725664cce8ed3c73c5ec1c9ab
反应方程式
反应物
反应条件
后处理
- 1温度The mixture was cooled to room temperature
- 2浓缩concentrated
- 3其他to give black residue which
- 4萃取The aqueous phase was extracted with EtOAc (4×30 mL)
- 5洗涤The combined organic phase was washed with brine (30 mL)
- 6干燥dried over anhydrous Na2SO4
- 7浓缩concentrated
- 8其他to give black green residue which
- 9其他was purified by CombiFlash (12 g silica gel column; EtOAc/Hexane: 0-100%)
实验过程
(R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine (104 mg, 0.244 mmol, 1.0 equiv), tert-butyl 2-(4-iodo-1H-pyrazol-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate (112 mg, 0.268 mmol, 1.1 equiv) were added to a RBF (25 mL). It was vacuumed and refilled with N2 (3 times). Dioxane (1.0 mL) and a solution of Na2CO3 (2.0 M, 0.4 mL) were added sequentially. It was vacuumed again and refilled with N2 (3 times). Pd(PPh3)2Cl2 catalyst (9 mg, 5 mol %) was added last. It was vacuumed and refilled with N2 (3 times). The mixture was then heated to 80° C. (oil bath) and stirred at this temperature under N2 for 24 hrs. The mixture was cooled to room temperature, and concentrated to give black residue which was treated with H2O (30 mL). The aqueous phase was extracted with EtOAc (4×30 mL). The combined organic phase was washed with brine (30 mL), dried over anhydrous Na2SO4, concentrated to give black green residue which was purified by CombiFlash (12 g silica gel column; EtOAc/Hexane: 0-100%) to afford 105 mg (yield 73%) of (R)-tert-butyl 2-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate as a pale yellow solid.