Potassium Phosphate, Tribasic → 3-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline

Participants

Reaction Conditions

Reaction Steps

A solution of 3-chloro-4-(2-chloropyridin-4-yloxy)-2-fluoroaniline (10 g, 36.8 mmol) in DMF (140 mL) and water (30 mL) was treated with 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (8.4 g, 40.5 mmol), K3PO4 (14.9 g, 73.6 mmol) and Pd(PPh3)4 (4.3 g, 3.7 mmol), sparged with N2 and heated at 80° C. for 12 h. The mixture was cooled to RT, poured into water and extracted with EtOAc (3×). The combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography to afford 3-chloro-2-fluoro-4-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)aniline (3.0 g, 26%). 1H NMR (400 MHz, DMSO-d6): δ 8.32 (d, J=6.0 Hz, 1 H), 8.24 (s, 1 H), 7.95 (s, 1 H), 7.15 (d, J=1.6 Hz, 1 H), 6.94 (d, J=8.8 Hz, 1 H), 6.80 (t, J=8.8 Hz, 1 H), 6.54-6.52 (m, 1 H), 5.51 (s, 2 H), 3.85 (s, 3H); MS (ESI): m/z 318.2 (M+H+).

Provenance & Evidence