4-Bromo-2-fluoroaniline → 5-(4-amino-3-fluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile

Participants

Reaction Conditions

Reaction Steps

4-Bromo-2-fluoroaniline (2.42 g, 12.8 mmol), 1-methyl-5-cyano-2-pyrroleboronic acid (2.3 g, 15.3 mmol), KF (2.45 g, 42.2 mmol), and Pd2(dba)3 (147 mg, 0.16 mmol) were added to a 100 mL round bottom flask under nitrogen. The flask was sealed and purged with nitrogen for 5 min. THF (32 mL) was added and the mixture was purged with nitrogen for an additional 5 min. A solution of tri-t-butylphosphine (10 wt % in hexanes) (0.95 mL, 0.32 mmol) was added via syringe and the mixture was stirred vigorously at 25° C. for 5 h. The mixture was diluted with 250 mL of EtOAc, filtered through a plug of silica gel, washed through with 200 mL of EtOAc and concentrated to give a crude brown/black semi-solid. Purification by flash chromatography (20% acetone/hexane) afforded 5-(4-amino-3-fluorophenyl)-1-methyl-1H-pyrrole-2-carbonitrile (0.76 g) as an off-white solid.

Provenance & Evidence