To a solution of indole-2-carboxylic acid (80 mg, 0.50 mmol) in N,N-dimethylformamide (1.5 mL) are added TBTU (139 mg, 0.43 mmol) and N,N-diisopropyl amine (0.126 mL, 0.74 mmol). Subsequently [1-(4-amino-2-fluorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl]acetic acid methyl ester (120 mg, 0.41 mmol) is added. The mixture is stirred at room temperature for 12 hours. After that an aqueous solution of K2CO3 (2 M, 0.5 mL) is added. The obtained mixture is flushed through Al2O3 with dichloromethane/methanol (9:1, 10 mL). The solvent is removed in vacuo to yield 82.3 mg of (1-(2-fluoro-4-[(1H-indole-2-carbonyl)amino]benzyl)-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid methyl ester (ESI mass spectrum: [M+H]+=435; Retention time HPLC: 0.41 min (method N). b) (1-(2-Fluoro-4-[(1H-indole-2-carbonyl)amino]benzyl)-3,5-dimethyl-1H-pyrazol-4-yl)acetic acid methyl ester (82 mg, 0.19 mmol) is dissolved in methanol (0.5 mL). An aqueous solution of NaOH (4M, 0.3 mL) is added and the mixture is stirred at room temperature for 2 hours. The resulting mixture is diluted with methanol/water, the solid is filtered off and after evaporation the residue is purified by HPLC (Gilson, XRS Pursuit, methanol/H2O+0.1% conc. NH3). The fractions containing the title compound are concentrated and lyophilized to yield 15 mg of the title compound (ESI mass spectrum: [M+H]+=421; Retention time HPLC: 1.04 min (method G)).
