5-((1-Ethylpiperidin-4-yl)methyl)-N-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine. 541-Benzylpiperidin-4-yl)methyl)-N-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine was synthesized from 1-benzyl-4-methylenepiperidine and 5-bromo-N-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine following the procedure described for N-phenyl-5-(piperidin-4-ylmethyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine. 5-((1-Benzylpiperidin-4-yl)methyl)-N-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine (0.165 g, 0.354 mmol) was dissolved in ethanol (30 mL) and treated with a catalytic amount of palladium on carbon (10 weight %). The reaction was stirred under an atmosphere of hydrogen gas overnight at room temperature. As only trace conversion was observed, a drop of acetic acid was added and the reaction was stirred at room temperature overnight. Most of the starting material was converted to the title compound contaminated with a minor amount of 5-(piperidin-4-ylmethyl)-N-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine. The catalyst was removed by filtration washed with methanol and the filtrate was concentrated under reduced pressure. The residue was purified by semi-preparative HPLC (20-70% acetonitrile+0.1% trifluoroacetic acid in water+0.1% trifluoroacetic acid, 3 injections, 30 min.). The desired fractions were combined and neutralized with a STRATA cationic resin exchange column. The eluate was concentrated under reduced pressure and dried in a vacuum oven for 5 h. 541-Ethylpiperidin-4-yl)methyl)-N-(4-(trifluoromethyl)phenyl)-[1,2,4]triazolo[1,5-a]pyridin-2-amine (0.019 g, 0.047 mmol, 13.29% yield) was isolated as a off-white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm) 10.18 (s, 1H), 7.91 (d, J=8.59 Hz, 2H), 7.64 (d, J=8.59 Hz, 2H), 7.48-7.59 (m, 2H), 6.95 (s, 1H), 3.03 (d, J=6.64 Hz, 2H), 2.82 (br s, 2H), 2.26 (s, 2H), 1.99 (br s, 1H), 1.78 (br s, 2H), 1.55 (br s, 2H), 1.33 (br s, 2H), 0.89-1.02 (m, 3H); 19F NMR (400 MHz, DMSO-d6) δ (ppm)-59.9 ppm; MS (ESI): m/z 404.2 [M+1]+.
