Boronic Acid → (3-Amino-2,6-difluoro-phenyl)-[5-(4-chlorophenyl)-1-(2,6-dichlorobenzoyl)pyrrolo[2,3-b]pyridin-3-yl]methanone

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Reaction Steps

Under a nitrogen atmosphere, a 50-liter flask is charged with compound 5 (1.735 kg, 3.304 mol) prepared from Example 3 in 2-methyl-THF, boronic acid 6 (0.877 kg, 5.617 mol), PdCl2(PPh3)2 (0.116 kg, 0.165 mol) and an aqueous sodium bicarbonate (0.833 kg, 9.912 mol) solution (8.7 L). The reaction mixture is degassed and heated to reflux for 7 hrs and stirred at room temperature overnight. Compound 6 (129.0 g) and PdCl2(PPh3)2 (6.6 g) are added again and the reaction mixture is heated to reflux for another 5 hrs. Celite (1.735 kg) is added and the mixture is stirred for 30 minutes and then filtered through a pad of celite. The residue is washed with 2-methyl-THF. The organic layer is separated, washed with a 10% NaCl aqueous solution (4 L) for three times, further washed with a 20% NaCl aqueous solution, filtered, and dried over Na2SO4. The filtrate is concentrated by removing about 80-85% of solvent, added ethyl acetate (3.5 L) and stirred overnight. The mixture is filtered and washed with ethyl acetate (2×3.5 L) twice. Compound 7, is isolated after removing the solvents and drying at 45° C. for 48 hrs (2.765 kg, 74% yield).

Provenance & Evidence