Trifluoroacetic acid → 6-Chloro-5-(1H-pyrazol-5-yl)-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Participants

Reaction Conditions

Reaction Steps

K3PO4 (5.70 g, 26.8 mmol), 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (3.73 g, 13.42 mmol) and Pd(PPh3)4 (0.517 g, 0.447 mmol) were added to a solution of 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 32.2, 4.0 g, 8.95 mmol) in toluene (45 mL) added under an argon atmosphere and the RM was stirred at 80° C. for 5 h. The RM was filtered through Hyflo®, which was washed with EtOAc. The filtrate and washings were combined and the solvent was evaporated off under reduced pressure to give a residue which was purified by flash chromatography (Silica gel column, 80 g, n-hexane/EtOAc from 9:1 to 1:1) and triturated under n-hexane, filtered and dried to afford a solid, a portion of which (1.5 g, 3.02 mmol) was treated with TFA (1.163 mL, 15.10 mmol) in DCM (20 mL) and stirred at RT for 4 h. TFA (1.16 mL) was added and the mixture was allowed to stand for 3 days at RT. The solvent was evaporated off under reduced pressure and the residue was diluted with EtOAc, treated with sat. aq. Na2CO3 and extracted with EtOAc. The combined organic layers were washed with brine (50 mL), dried over Na2SO4 and the solvent was evaporated off under reduced pressure to give a crude product which was purified by flash chromatography (Silica gel column, 40 g, n-hexane/EtOAc from 9:1 to 1:1) to afford the title product as beige crystals. UPLC-MS (Condition 3) tR=1.02 min, m/z=383.1 [M+H]+.

Provenance & Evidence