Trifluoroacetic acid → Ammonium Acetate

Participants

Reaction Steps

To a solution containing tert-butyl 2-(4-fluorophenyl)-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-b]pyridazine-3-carbonyl(methyl)carbamate (0.044 g, 0.065 mmol) and dichloromethane (4 mL) was added TFA (0.41 mL, 5.3 mmol) at room temperature. The solution was maintained for 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) to afford 2-(4-fluorophenyl)-N-methyl-5-(2-methyl-5-(1-phenylcyclopropylcarbamoyl)phenyl)pyrazolo[1,5-b]pyridazine-3-carboxamide as a white solid. Preparative HPLC: retention time: 12.6 min. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.68 (d, J=2.51 Hz, 1 H), 8.43 (d, J=2.26 Hz, 1 H), 7.85 (dd, J=7.91, 1.88 Hz, 1 H), 7.72-7.81 (m, 3 H), 7.45 (d, J=8.03 Hz, 1 H), 7.28-7.36 (m, 5 H), 7.16-7.27 (m, 3 H), 5.90 (d, J=4.52 Hz, 1 H), 2.90 (d, J=5.02 Hz, 3 H), 2.43 (s, 3 H), 1.42 (s, 2 H), 1.35-1.41 (m, 2 H). LCMS retention time: 2.310 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-V is 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% H2O/10 mM TFA and solvent B was 10% H2O/90% methanol/10 mM TFA. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 520 (MH+).

Provenance & Evidence