Dimethylformamide → 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Participants

Reaction Conditions

Reaction Steps

DMF (1.927 mL, 24.89 mmol) and SOCl2 (18.17 mL, 249 mmol) were added to a suspension of 6-chloro-5-iodo-3-pyridinecarboxylic acid (24 g, 83 mmol) in toluene (165 mL) and the RM was stirred at 80° C. for 1 h. The solvent was evaporated off under reduced pressure and the residue was dissolved in THF (165 mL). DIPEA (29.0 mL, 166 mmol) was added and the mixture was cooled down to −15° C., treated dropwise with a solution of 4-(trifluoromethoxy)aniline (15.43 g, 87 mmol) in THF (165 mL) and was stirred at RT for 1 h. The solvent was off under reduced pressure and the residue was dissolved in TBME (500 mL), washed with 1N HCl, a sat. aq. solution of NaHCO3 and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure and the product was recrystallized from EtOAc/n-heptane to afford the title compound as a white solid. UPLC-MS (Condition 2) tR=1.23 min, m/z=440.8 [M−H]−.

Provenance & Evidence