反应详情

6-(N-ethylmethylsulfonamido)-2-(4-fluorophenyl)-5-(5-(1-(4-fluorophenyl)cyclopropylcarbamoyl)-2-methylphenyl)-N-methylpyrazolo[1,5-a]pyridine-3-carboxamide was prepared from 3-(6-(N-ethylmethylsulfonamido)-2-(4-fluorophenyl)-3-(methylcarbamoyl)pyrazolo[1,5-a]pyridin-5-yl)-4-methylbenzoic acid (0.024 g, 0.046 mmol) and 1-(4-fluorophenyl)cyclopropanamine hydrochloride (0.013 g, 0.069 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), 15 min. gradient) to afford 6-(N-ethylmethylsulfonamido)-2-(4-fluorophenyl)-5-(5-(1-(4-fluorophenyl)cyclopropylcarbamoyl)-2-methylphenyl)-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 8.54 (s, 1H), 8.29 (s, 1H), 7.82 (br. s., 2H), 7.65-7.77 (m, 2H), 7.40 (d, J=7.78 Hz, 2H), 7.31-7.38 (m, 3H), 7.22-7.30 (m, 4H), 6.90-7.00 (m, 2H), 5.55 (d, J=4.77 Hz, 1H), 3.42 (br. s., 1H), 3.00-3.12 (m, 2H), 2.78-2.90 (m, 4H), 2.34 (s, 3H), 1.62 (br. s., 2H), 1.25-1.37 (m, 5H), 1.08 (br. s., 3H). LCMS retention time: 1.920 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 5% CH3CN/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% CH3CN/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode. m/z 658 (MH+).

1. customThe resultant residue was purified