Reaktion #580964

Reaktionsgleichung

N2

7-cyclobutyl-5-iodo-imidazo[5,1-f][1,2,4]triazin-4-ylamine

8-fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[2,3,2]dioxaborolan-2-yl)quinoline

cesium carbonate

sodium bicarbonate

→

title compound

7-Cyclobutyl-5-(8-fluoro-2-phenyl-quinolin-7-yl)-imidazo[5,1-f][1,2,4]triazin-4-ylamine

Lösungsmittel

dimethoxyethane

H2O

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturmaintained at this temperature for 16 hours
2. 2
   TemperaturAfter cooling
3. 3
   Extraktionextracted with EtOAc (3×50ml)
4. 4
   WaschenThe combined organics were washed with brine (2×50ml)
5. 5
   Trocknendried over magnesium sulfate (MgSO4)
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated
8. 8
   SonstigeThe material was purified by chromatography on silica gel [eluting with 100% DCM→0.4% MeOH in DCM]

Vorschrift

A stirred solution of 7-cyclobutyl-5-iodo-imidazo[5,1-f][1,2,4]triazin-4-ylamine (40 mg, 0.1 mmol), 8-fluoro-2-phenyl-7-(4,4,5,5-tetramethyl-[2,3,2]dioxaborolan-2-yl)quinoline (52 mg, 0.15 mmol) and cesium carbonate (50 mg, 0.15 mmol) in dimethoxyethane (DME) (1.67 mL) and H2O (0.33 mL) was degassed for 10 minutes using N2. Tetrakis(triphenylphosphine)palladium(0) (7 mg, 0.006 mmol) was added, and the reaction was heated to 75° C. and maintained at this temperature for 16 hours. After cooling, the reaction mixture was poured into saturated sodium bicarbonate (NaHCO3) solution (50 ml) and extracted with EtOAc (3×50ml). The combined organics were washed with brine (2×50ml), dried over magnesium sulfate (MgSO4), filtered and concentrated. The material was purified by chromatography on silica gel [eluting with 100% DCM→0.4% MeOH in DCM] resulting in the title compound as a white solid; 1H NMR (CDCl3, 400MHz) δ 2.06-1.99 (m, 1H), 2.10-2.20 (m, 1H), 2.42-2.52 (m, 2H), 2.62-2.71 (m, 2H), 4.14-4.21 (m, 1H), 7.45-7.56 (m, 3H), 7.74 (d, J=8.6 Hz, 1H), 7.79 (dd, J=6.3 Hz, 6.3 Hz, 1H), 7.87 (s, 1H), 7.99 (d, J=8.8 Hz, 1H), 8.21 (d, J=6.8 Hz, 2H), 8.27 (d, J=7.6 Hz, 1H); MS (ES+): m/z 411.00 (100) [MH+], HPLC: tR=3.53 min (MicromassZQ, polar—5 min).

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