تفاعل #674302
ord-92bcbbf725664cce8ed3c73c5ec1c9ab
معادلة التفاعل
المتفاعلات
الكواشف
ظروف التفاعل
المعالجة
- 1درجة الحرارةThe mixture was cooled to room temperature
- 2تركيزconcentrated
- 3أخرىto give black residue which
- 4استخلاصThe aqueous phase was extracted with EtOAc (4×30 mL)
- 5غسيلThe combined organic phase was washed with brine (30 mL)
- 6تجفيفdried over anhydrous Na2SO4
- 7تركيزconcentrated
- 8أخرىto give black green residue which
- 9أخرىwas purified by CombiFlash (12 g silica gel column; EtOAc/Hexane: 0-100%)
الإجراء التجريبي
(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.