Reaction #45831

Reaction equation

Potassium phosphate

2-amino-5-bromo-4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-methyl-3-nitrobenzonitrile

phenylboronic acid

→

compound

Yield 90.2%

4-Amino-6-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-2-methyl-5-nitrobiphenyl-3-carbonitrile

Yield 90.2%

Solvents

dioxane

Conditions

Workup

1. 1
   Otherby purging with nitrogen
2. 2
   Temperatureheating
3. 3
   Temperatureunder reflux for 18 hours
4. 4
   TemperatureAfter cooling
5. 5
   workup.ADDITIONwater was added
6. 6
   Extractionfollowed by extraction with ethyl acetate
7. 7
   WashThe organic layer was washed with saturated brine
8. 8
   Dryingdried over anhydrous sodium sulfate
9. 9
   OtherThe solvent was evaporated away under reduced pressure
10. 10
    Washeluted with a mixed solvent of chloroform/methanol (2:1

Procedure

Potassium phosphate (115 mg, 0.54 mmol) and Pd(PPh3)4 (16 mg, 5 mol %) were added to a dioxane (3 ml) solution of 2-amino-5-bromo-4-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-6-methyl-3-nitrobenzonitrile (I-267) (100 mg, 0.27 mmol) and phenylboronic acid (40 mg, 0.33 mmol), followed by purging with nitrogen and heating under reflux for 18 hours. After cooling, water was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, then dried over anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the residue was subjected to column chromatography, and eluted with a mixed solvent of chloroform/methanol (2:1, v/v) to obtain the entitled compound (89 mg, 90%) as a dark red solid.

Source