Reaction #312625

Reaction equation

2-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde

cesium carbonate

toluene IPA water

5-bromo-pyrazin-2-ylamine

→

product

Yield 35.9%

5-(5-Amino-pyrazin-2-yl)-2-(2,6-dimethyl-morpholin-4-yl)-3,4-difluoro-benzaldehyde

Yield 35.9%

Solvents

EtOAc

water

Conditions

Workup

1. 1
   TemperatureThe mixture was cooled to room temperature
2. 2
   OtherThe phases were separated
3. 3
   Extractionthe aqueous phase was re-extracted with EtOAc (×2)
4. 4
   DryingThe combined organic layers were dried over MgSO4
5. 5
   Concentrationconcentrated
6. 6
   OtherPurified by column chromatography
7. 7
   Washeluting with ethyl acetate in hexanes (10-60%)

Procedure

To a suspension of 2-(2,6-Dimethyl-morpholin-4-yl)-3,4-difluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzaldehyde (0.500 g, 1.3 mmol) and cesium carbonate (1.2 g, 3.6 mmol) in previously degassed toluene/IPA/water (4/4/1) mixture (2.5 mL) was added 5-bromo-pyrazin-2-ylamine (Maybridge, 0.208 g, 1.2 mmol) under nitrogen. Tetrakis(triphenylphosphine)palladium-(0) (0.055 g, 0.05 mmol) was added at room temperature and the reaction was heated at 85° C. for 3.5 hrs. The mixture was cooled to room temperature, diluted with EtOAc and water then neutralized. The phases were separated and the aqueous phase was re-extracted with EtOAc (×2). The combined organic layers were dried over MgSO4 and concentrated. Purified by column chromatography eluting with ethyl acetate in hexanes (10-60%) to obtain 150 mgs of product. 1H NMR (400 MHz, CHLOROFORM-d) d ppm 1.28 (d, J=6.4 Hz, 6H), 2.97 (m, 2H), 3.34 (m, 2H), 4.18 (m, 2H), 4.78 (s, 2H), 8.08 (d, J=1.6 Hz, 1H), 8.19 (dd, J=8.4, 2.1 Hz, 1H), 8.44 (m, 1H), 10.37 (s, 1H); MS(APCl+) m/z 349 (MH+).

Source