Sodium 2-methylbutan-2-olate (0.281 g, 2.55 mmol) was added to a stirring solution of methyl 5-(6-chloro-2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-b]pyridin-5-yl)-2-methoxynicotinate (0.120 g, 0.255 mmol), 2,2,2-trifluoroethanamine (0.253 g, 2.55 mmol), Chloro[2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (0.020 g, 0.026 mmol), in dioxane (2.55 ml) at 100° C. Immediately, the reaction mixture turned to a dark amber color. LCMS after 1 h shows complete conversion to the desired coupled product with simultaneous deprotection of the tButyl ester. The reaction mixture was cooled to rt and concentrated to a dry solid. The resultant solid was then taken up in EtOAc and diluted with 1 M HCl. The layers were separated and the aq layer was extracted with EtOAc (2×15 mL). The layers were washed with water, brine, dried over Na2SO4, filtered and concentrated to give a yellow solid. This solid was then triturated with DCM (25 mL) for 3 h. The solids were filtered to give the desired 5-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)-2-methoxynicotinic acid (110 mg, 0.21 mmol, 83% yield) as a yellow solid. LC-MS retention time: 1.68 min; m/z (observed boronic acid M+H): 519. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna 3u C18 2.0×30 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 1 mL/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 10% acetonitrile/90% H2O/0.1% trifluoroacetic acid and solvent B was 10% H2O/90% acetonitrile/0.1% trifluoroacetic acid. MS data was determined using a Micromass Platform for LC in electrospray mode. 1H NMR (500 MHz, METHANOL-d4) δ 8.38 (d, J=2.5 Hz, 1H), 8.29 (d, J=2.5 Hz, 1H), 7.91 (dd, J=8.2, 6.1 Hz, 3H), 7.69 (s, 1H), 7.23-7.19 (m, 3H), 4.18 (d, J=9.3 Hz, 2H), 4.07 (s, 3H), 2.91 (s, 3H).
