Reaktion #674302

Reaktionsgleichung

N2

N2

(R)-3-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-amine

tert-butyl 2-(4-iodo-1H-pyrazol-1-yl)-7-azaspiro[3.5]nonane-7-carboxylate

N2

Na2CO3

→

(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

Ausbeute 73.0%

Lösungsmittel

H2O

Dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was cooled to room temperature
2. 2
   Einengenconcentrated
3. 3
   Sonstigeto give black residue which
4. 4
   ExtraktionThe aqueous phase was extracted with EtOAc (4×30 mL)
5. 5
   WaschenThe combined organic phase was washed with brine (30 mL)
6. 6
   Trocknendried over anhydrous Na2SO4
7. 7
   Einengenconcentrated
8. 8
   Sonstigeto give black green residue which
9. 9
   Sonstigewas purified by CombiFlash (12 g silica gel column; EtOAc/Hexane: 0-100%)

Vorschrift

(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.

Quelle