Water → HCID 72201588, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-chloro-5-iodo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 56.1, 15 g, 33.9 mmol) (15 g, 33.9 mmol), pyridin-3-ylboronic acid (4.73 g, 37.3 mmol), PdCl2(dppf) (1.240 g, 1.695 mmol), K3PO4 (21.58 g, 102 mmol), water (4 mL) and toluene (160 mL) was stirred at 100° C. overnight. The solvent was evaporated off under reduced pressure and the residue was treated with water and extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure. The residue was purified by flash chromatography (Silica gel column, 500 g, EtOAc/MeOH from 0 to 2% MeOH). Fractions containing the pure product were combined and the solvent was evaporated off under reduced pressure to give a residue which was dissolved in MeOH (50 mL), stirred overnight with Si-Thiol (1 g), filtered and the filtrate was evaporated off under reduced pressure to give the title compound as a beige solid. UPLC-MS (Condition 7) tR=1.1 min, m/z=392 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.42 (d, J=8.68 Hz, 2H) 7.60 (dd, J=7.89, 4.83 Hz, 1H) 7.88 (d, J=9.05 Hz, 2H) 8.07 (dt, J=7.82, 1.90 Hz, 1H) 8.49 (d, J=2.32 Hz, 1H) 8.71 (dd, J=4.83, 1.41 Hz, 1H) 8.81 (d, J=2.08 Hz, 1H) 9.00 (d, J=2.20 Hz, 1H) 10.68 (s, 1H).

Provenance & Evidence