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

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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, 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 stirred at RT for 1 h. The solvent was off under reduced pressure and the residue was dissolved in TBME (500 mL), washed with 1 M 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. HPLC (Condition 4) tR=6.36 min, UPLC-MS (Condition 3) tR=1.23 min, m/z=441.1 [M−H]−.

Provenance & Evidence