Reaktion #537632

Reaktionsgleichung

water

5-Chloro-4-(2-chloropyridin-4-yloxy)-2-fluorobenzenamine

1-methyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

cesium carbonate

→

5-chloro-2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine

Ausbeute 77.3%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeArgon was bubbled through the mixture for 5 minutes
2. 2
   SonstigeThe flask was fitted with a reflux condenser
3. 3
   Sonstigeflushed with argon
4. 4
   TemperaturThe reaction mixture was then cooled to RT
5. 5
   workup.ADDITIONdiluted with a 4:1 mixture of ethyl acetate and THF
6. 6
   ExtraktionThe solution was extracted with 10% aqueous LiCl (2×150 mL) and brine (100 mL)
7. 7
   Trocknendried (MgSO4)
8. 8
   Sonstigeevaporated under reduced pressure
9. 9
   Sonstigepurified via silica gel chromatography (ethyl acetate/hexanes)

Vorschrift

5-Chloro-4-(2-chloropyridin-4-yloxy)-2-fluorobenzenamine (1.177 g, 4.31 mmol) and 1-methyl(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.166 g, 5.60 mmol) were dissolved in DMF (16.16 ml), cesium carbonate (4.21 g, 12.93 mmol) was added, followed by water (5.39 ml). Argon was bubbled through the mixture for 5 minutes, and then palladium tetrakistriphenylphosphine (0.249 g, 0.215 mmol) was added. The flask was fitted with a reflux condenser, flushed with argon, and heated in a 90° C. oil bath under a balloon of argon for 4 hours. The reaction mixture was then cooled to RT and diluted with a 4:1 mixture of ethyl acetate and THF. The solution was extracted with 10% aqueous LiCl (2×150 mL) and brine (100 mL), dried (MgSO4), evaporated under reduced pressure and purified via silica gel chromatography (ethyl acetate/hexanes) to yield 5-chloro-2-fluoro-4-(2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)benzenamine as a tan solid (1.062 g, 77% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.31 (d, 1H), 8.24 (s, 1H), 7.95 (s, 1H), 7.20 (d, 1H), 7.13 (d, 1H), 6.92 (d, 1H), 6.52 (dd, 1H), 5.49 (s, 2H), 3.84 (s, 3H); MS (ESI) m/z: 319.1 (M+H+).

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