Hydrochloric Acid → 5-bromo-6-chloro-N-(4-((trifluoromethyl)thio)phenyl)nicotinamide

Participants

Reaction Conditions

Reaction Steps

DMF (0.12 mL) was added followed by slow addition of SOCl2 (0.73 mL, 10 mmol) to a mixture of 5-bromo-6-chloro-nicotinic acid (473 mg, 2 mmol) in toluene (5 mL), and the RM was then stirred at 80° C. for 1 h. After cooling at RT, the toluene was evaporated off under reduce pressure and the residue was dissolved in THF (0.4 mL). DIPEA (0.7 mL, 4 mmol) was added and the solution was cooled to 0° C. under nitrogen. 4-trifluoromethylsulfanyl-aniline (438 mg, 2.2 mmol) in THF (1 mL) was then added dropwise and the RM was stirred at 0° C. for 2 h. The RM was diluted with TBME (50 mL), treated with 1 M HCl and extracted with TBME. The combined extracts were washed with 1 M aq. NaOH and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure and the product was crystallized from TBME/n-hexane to give the title compound as an off-white crystalline powder. HPLC (Condition 4) tR=6.63 min, UPLC-MS (Condition 3) tR=1.33 min, m/z=411.1 [M+H]+.

Provenance & Evidence