Diisopropylethylamine → Ammonium Acetate

Participants

Reaction Steps

To a solution containing 1-(pyridin-2-yl)cyclopropanamine hydrochoride (0.0078 g, 0.046 mmol), diisopropylethylamine (0.049 mL, 0.28 mmol), 5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-2-methoxy-6-methylnicotinic acid (0.016 g, 0.035 mmol) and DMF (0.24 mL) was added HATU (0.027 g, 0.071 mmol) in one portion. The solution was maintained at room temperature for 1 h and concentrated. Purification of the resultant residue 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-(6-methoxy-2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)pyridin-3-yl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 12.49 min. 1H NMR (400 MHz, MeOD) δ ppm 8.55 (1H, d, J=7.03 Hz), 8.41-8.46 (1H, m), 8.20 (1H, s), 7.82-7.93 (2H, m), 7.72 (1H, td, J=7.78, 1.76 Hz), 7.52 (1H, d, J=8.03 Hz), 7.15-7.27 (3H, m), 6.95 (1H, t, J=6.90 Hz), 4.19 (3H, s), 2.91 (3H, s), 2.49 (3H, d, J=1.00 Hz), 1.65-1.73 (2H, m), 1.36-1.42 (2H, m). LCMS: retention time: 1.695 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 u, C18, 3.0×50 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 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 569 (MH+).

Provenance & Evidence