To a solution of 2-(4-(methoxycarbonyl)-1H-pyrazol-1-yl)acetic acid (ChemCollect GmbH, 401 mg, 2.175 mmol) in toluene (10 mL) was added thionyl chloride (0.317 mL, 4.35 mmol) and the reaction mixture was stirred at 90° C. for 2 h. The solvent was removed under reduced pressure and the residue was added to a solution of methyl 4-amino-6-chloro-4′-(piperidin-1-yl)-[1,1′-biphenyl]-3-carboxylate (Intermediate 48) (500 mg, 1.45 mmol) in dichloromethane (10 mL). The reaction mixture was stirred at room temperature overnight. Solvent was removed under reduced pressure and water was added. Precipitate was observed, solid was filtered and dried to give the title compound methyl 1-(2-((2-chloro-5-(methoxycarbonyl)-4′-(piperidin-1-yl)-[1,1′-biphenyl]-4-yl)amino)-2-oxoethyl)-1H-pyrazole-4-carboxylate (720 mg, 1.409 mmol, 97% yield) as a cream solid. LCMS: (M+H)+=511; Rt=4.04 min.
