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Sodium 2′-(dicyclohexylphosphino)-2,6-dimethoxybiphenyl-3-sulfonate (9.8 mg, 0.019 mmol), PdOAc2 (2.2 mg, 9.6 μmol), Cs2CO3 (93 mg, 0.29 mmol), 3-boronobenzoic acid (24 mg, 0.14 mmol) was added to a stirring solution of 2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-c]pyridin-5-yl trifluoromethanesulfonate (40 mg, 0.096 mmol) in DMF (1.7 mL) and Water (170 μL). It was degassed and heated to 60° C. and allowed to stir for 1 hour. The mixture was diluted with ethyl acetate and washed with 1M HCl, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated to give 3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)furo[2,3-c]pyridin-5-yl)benzoic acid. The residue was diluted with DMF (1.7 mL) and treated with HATU (55 mg, 0.15 mmol), 1-(pyridin-2-yl)cyclopropanamine dihydrochloride (24 mg, 0.12 mmol), followed by DIEA (84 μL, 0.48 mmol) at room temperature. The reaction was allowed to stir for 1 hr. The mixture was diluted with EtOAc and washed with 1M NaOH, and sat NaCl. The organic phase was dried over Na2SO4, filtered and concentrated and was purified by preparative reverse phase HPLC on a C18 column using a suitably buffered H2O/MeOH gradient, and concentrated to give 2-(4-fluorophenyl)-N-methyl-5-(3-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)furo[2,3-c]pyridine-3-carboxamide (14 mg, 0.028 mmol, 29% yield) consistent by LCMS and NMR. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.45 (1H, s), 9.14 (1H, s), 8.67 (1H, s), 8.55-8.61 (1H, m), 8.51 (1H, d, J=5.02 Hz), 8.34 (1H, d, J=7.78 Hz), 8.27 (1H, s), 8.07 (2H, dd, J=8.78, 5.52 Hz), 7.99 (1H, d, J=7.78 Hz), 7.80-7.91 (1H, m), 7.64 (1H, t, J=7.78 Hz), 7.49 (1H, d, J=8.03 Hz), 7.45 (2H, t, J=8.91 Hz), 7.25-7.34 (1H, m), 2.89 (3H, d, J=4.52 Hz), 1.58-1.69 (2H, m), 1.36-1.45 (2H, m). LC-MS retention time: 1.26 min; m/z (MH+): 507. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters SunFire 5u C18 4.6×50 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 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 3 min, a hold time of 1 min, and an analysis time of 4 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. Additional HPLC method: Solvent A=5% CH3CN/95% H2O/0.1% TFA, Solvent B=95% CH3CN/5% H2O/0.1% TFA, Start % B=10, Final % B=100, Gradient time=15 min, Stop time=18 min, Flow Rate=1 ml/min. Column: Waters Sunfire C-18, 4.6×150 mm, 3.5 mm, Rt=13.20 min, purity=100%; Column: Waters Xbridge Phenyl column 4.6×150 mm, 3.5 mm, Rt=12.12 min, purity=100%.
