1-(2-Pyridyl)cyclopropylamine Dihydrochloride → Ammonium Acetate

Participants

Reaction Steps

4-fluoro-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide was prepared from 3-(4-fluoro-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid (0.065 g, 0.154 mmol) and 1-(pyridin-2-yl)cyclopropanamine dihydrochloride (0.032 g, 0.154 mmol). The resultant residue was purified using preparative HPLC (Waters—Xbridge, 50×100 mm, 5 micron, C18 column; 0.1M ammonium acetate, 10-100% B (B=5% H2O/CH3CN)/A (A=95% H2O/CH3CN), 20 min. gradient) to afford 4-fluoro-2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-(pyridin-2-yl)cyclopropylcarbamoyl)phenyl)pyrazolo[1,5-a]pyridine-3-carboxamide as a white solid. Preparative HPLC: retention time: 9.5 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.48 (d, J=4.02 Hz, 1H), 8.37 (d, J=7.03 Hz, 1H), 7.78-7.90 (m, 4H), 7.60 (td, J=7.78, 1.76 Hz, 1H), 7.44 (d, J=8.03 Hz, 1H), 7.38 (d, J=7.78 Hz, 1H), 7.13-7.22 (m, 2H), 7.04-7.13 (m, 2H), 6.76 (t, J=6.78 Hz, 1H), 5.87 (d, J=4.52 Hz, 1H), 2.97 (d, J=5.02 Hz, 3H), 2.35 (s, 3H), 1.69-1.80 (m, 2H), 1.37-1.48 (m, 2H). LCMS retention time: 1.642 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% methanol/90% water/10 mM TFA and solvent B was 10% water/90% methanol/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 538 (MH+).

Provenance & Evidence