Formic Acid → US9321721, Example 1

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-{4-[({[2-fluoro-5-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenyl}prop-2-ynamide (31.0 mg, 0.085 mmol), iodobenzene (0.010 mL, 0.089 mmol), diethylamine (0.029 mL, 0.281 mmol), formic acid (0.0083 mL, 0.221 mmol), and bis(dibenzylideneacetone)palladium(0) (3.4 mg, 0.006 mmol) in 1.1 mL EtOAc (degassed) was heated at 75° C. After 2 hours, an additional 2 mg bis(dibenzylideneacetone)palladium(0) was added and the reaction continued for 18 hours. The reaction was partitioned between EtOAc and H2O/brine mixture. The EtOAc layer was washed with dilute aqueous HCl, then aqueous Na2CO3, brine, dried with anhydrous Na2SO4 and rotary evaporated. The crude product was chromatographed eluting with EtOAc/CHCl3 and the resulting solid again chromatographed with MeOH/CHCl3 to give the title compound as an off-white solid (8.8 mg, 23%). 1H NMR (Acetone-d6) δ: 8.79 (dd, J=7.5, 2.2 Hz, 1H), 8.43 (d, J=2.9 Hz, 1H), 8.41 (s, 1H), 7.39-7.44 (m, 2H), 7.27-7.39 (m, 7H), 7.11-7.16 (m, 3H), 6.76 (br. s., 1H), 6.49 (s, 1H)

Provenance & Evidence