Potassium Phosphate, Tribasic → 5-chloro-2-fluoro-4-(3-(1-methyl-1H-pyrazol-yl)pyridin-4-yloxy)benzenamine

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-(3-bromopyridin-4-yloxy)-5-chloro-2-fluorobenzenamine, (0.300 g, 0.945 mmol) in n-butanol (5 mL) was added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.236 g, 1.134 mmol), S-Phos (0.078 g, 0.189 mmol), Pd2(dba)3 (0.087 g, 0.094 mmol) and potassium phosphate (0.602 g, 2.83 mmol). The resulting mixture was degassed and heated in a sealed tube at 100° C. for 20 h. The solvent from the reaction mixture was completely evaporated. The residue was stirred in a mixture of CH2Cl2-MeOH (1:1), filtered, rinsed, dried and subjected to chromatography (50-100% EtOAc-hexanes) to provide 5-chloro-2-fluoro-4-(3-(1-methyl-1H-pyrazol-yl)pyridin-4-yloxy)benzenamine, (0.148 g, 49.1% yield) as white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.80 (s, 1H), 8.20 (m, 2H), 8.01 (s, 1H), 7.24 (d, J=8.5 Hz, 1H), 6.95 (d, J=8.5 Hz, 1H), 6.51 (d, J=5.6 Hz, 1H), 5.51 (s, 2H), 3.88 (s, 3H); MS (ESI) m/z: 319.1 (M+H+).

Provenance & Evidence