Diisopropylethylamine → Ammonium Acetate

Participants

Reaction Steps

To a solution containing 1-(3-methyl-1,2,4-oxadiazol-5-yl)cyclopropanaminium 2,2,2-trifluoroacetate (0.021 g, 0.083 mmol), diisopropylethylamine (0.08 mL, 0.51 mmol), 3-fluoro-5-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid (0.028 g, 0.064 mmol) and DMF (0.43 mL) was added HATU (0.048 g, 0.13 mmol) in one portion. The solution was maintained at room temperature for 1 h 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-5-(3-fluoro-2-methyl-5-(1-(3-methyl-1,2,4-oxadiazol-5-yl)cyclopropylcarbamoyl)phenyl)-2-(4-fluorophenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 8.5 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.35 (d, J=7.03 Hz, 1H), 7.77-7.88 (m, 2H), 7.61 (dd, J=9.54, 1.51 Hz, 1H), 7.54 (s, 1H), 7.27-7.33 (m, 1H), 7.13-7.22 (m, 2H), 6.71 (t, J=6.65 Hz, 1H), 5.92 (d, J=4.52 Hz, 1H), 2.97 (d, J=5.02 Hz, 3H), 2.32 (s, 3H), 2.22 (s, 3H), 1.77-1.87 (m, 2H), 1.55-1.65 (m, 2H). LCMS retention time: 2.137 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Phenomenex-Luna, 10 micron, 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 3 min, a hold time of 1 min, and an analysis time of 4 min where solvent A was 10% CH3OH/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3OH/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 561 (MH+).

Provenance & Evidence