تفاعل #674295

معادلة التفاعل

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

المردود 45.0%

المذيبات

DME

ظروف التفاعل

المعالجة

1. 1
   أخرىIt was degassed again
2. 2
   workup.ADDITIONrefilled with N2 (2 times)
3. 3
   درجة الحرارة(heating bath) for 16 hrs
4. 4
   درجة الحرارةThe reaction mixture was cooled to room temperature
5. 5
   workup.ADDITIONH2O (30 mL) was added
6. 6
   استخلاصThe aqueous phase was extracted with EtOAc (30 mL) and DCM (3×30 mL)
7. 7
   تجفيفThe combined organic phase was dried over anhydrous Na2SO4
8. 8
   تركيزconcentrated by evaporation in vacuo
9. 9
   أخرىto give black residue which
10. 10
    أخرىwas purified by CombiFlash (40 g silica gel column, Hexane/EtOAc)

الإجراء التجريبي

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.

المصدر