Trifluoroacetic acid → Ammonium Acetate

Participants

Reaction Steps

To a solution containing 2-(1-aminocyclopropyl)pyrimidin-4-ol hydrochloride (0.025 g, 0.13 mmol), diisopropylethylamine (0.15 mL, 0.89 mmol), 5-(3-(tert-butoxycarbonyl(methyl)carbamyl)-4-fluoro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-4-methylbenzoic acid (0.070 g, 0.11 mmol) and DMF (0.74 mL) was added HATU (0.085 g, 0.22 mmol) in one portion. The solution was maintained at room temperature for 15 minutes. Dichloromethane (0.22 mL) was then added followed by trifluoroacetic acid (0.068 mL, 0.88 mmol). The solution was maintained for an additional 15 min and concentrated. The resultant residue was purified using preparative HPLC (Waters-Xbridge, 50×100 mm, 5 micron, C18 column; 0.1M ammonium acetate, 0-100% B (B=5% H2O/CH3CN)/A (A=95% H2O/CH3CN), 15 min. gradient) afforded 4-fluoro-2-(4-fluorophenyl)-5-(5-(1-(4-hydroxypyrimidin-2-yl)cyclopropylcarbamoyl)-4-methoxy-2-methylphenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 9.4 min. 1H NMR (400 MHz, MeOD) δ ppm 8.50 (1H, d, J=7.03 Hz), 7.78-7.90 (4H, m), 7.17-7.29 (3H, m), 6.87 (1H, t, J=6.90 Hz), 6.22 (1H, br. s.), 4.10 (3H, s), 2.87-2.93 (3H, m), 2.30-2.39 (3H, m), 1.81 (2H, br. s.), 1.40-1.48 (2H, m). LCMS: retention time: 1.798 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 3 micron, 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 4 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 5% CH3OH/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% CH3OH/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 585 (MH+).

Provenance & Evidence