Methylamine hydrochloride → Ammonium Acetate

Participants

Reaction Steps

5-(2-chloro-5-(isobutylcarbamoyl)phenyl)-2-(4-fluorophenyl)-6-(N-(2-hydroxyethyl)methylsulfonamido)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide was prepared from 5-(2-chloro-5-(isobutylcarbamoyl)phenyl)-2-(4-fluorophenyl)-6-(N-(2-hydroxyethyl)methylsulfonamido)pyrazolo[1,5-a]pyridine-3-carboxylic acid (0.027 g, 0.045 mmol) and methylamine hydrochloride (0.013 g, 0.18 mmol). 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), 10 min. gradient) to afford 5-(2-chloro-5-(isobutylcarbamoyl)phenyl)-2-(4-fluorophenyl)-6-(N-(2-hydroxyethyl)methylsulfonamido)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC retention time: 6 min. 1H NMR (500 MHz, MeOD) δ ppm 9.01 (s, 1H), 8.11 (s, 2H), 7.92 (s, 1H), 7.84-7.91 (m, 3H), 7.71 (d, J=8.55 Hz, 1H), 7.24-7.30 (m, 2H), 3.65 (s, 1H), 3.56 (s, 1H), 3.30 (d, J=1.22 Hz, 2H), 3.18-3.27 (m, 3H), 2.82-2.91 (m, 4H), 1.92 (dq, J=13.47, 6.80 Hz, 1H), 0.99 (d, J=6.71 Hz, 6H). LCMS retention time: 1.800 min. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Sunfire C18, 5 micron, C18, 4.6×50 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% CH3CN/90% H2O/10 mM TFA and solvent B was 10% H2O/90% CH3CN/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 638 (MNa+).

Provenance & Evidence