Combined 6-(4-(4-cyano-5-fluoro-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (100 mg, 0.296 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (47.9 mg, 0.355 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (68.0 mg, 0.355 mmol), DMF (Volume: 591 μl), and N-ethyl-N-isopropylpropan-2-amine (258 μl, 1.478 mmol). The orange solution was stirred at ambient temperature for 5 minutes then (S)-1-ethyl-3-methylpiperazine dihydrochloride (65.4 mg, 0.325 mmol) was added and the reaction was stirred at ambient temperature for 12 h. The reaction mixture was diluted with a pre-made solution of water:ethanol (1:1, 5 mL). The reaction was acidified to pH 5 using 1N HCl. The solution was left to stir slowly at ambient temperature overnight. The precipitate was filtered and the solids were washed with water:ethanol (1:1, 2 mL), then dried on the filter paper. The white solids were collected and dried further under vacuum. The dried solids were taken up in 10 volumes of water:ethanol (1:1) and stirred at reflux until the solution was almost completely translucent. The hot solution was filtered and then slowly cooled to ambient temperature and stirred slowly at ambient temperature overnight to give solids. The solids were filtered and washed with water:ethanol (1:1, 2 mL), partially dried on filter paper, then dried under vacuum to give the title compound (57.9 mg, 0.129 mmol, 43.7% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.06 (t, J=7.20 Hz, 3H) 1.30 (d, J=6.82 Hz, 3H) 2.14-2.28 (m, 1H) 2.31-2.45 (m, 4H) 2.53-2.60 (m, 2H) 2.81-3.06 (m, 2H) 3.13-3.43 (m, 2H) 4.08-4.62 (m, 1H) 7.64 (d, J=7.33 Hz, 1H) 7.96 (dd, J=8.84, 2.27 Hz, 1H) 8.08 (s, 1H) 8.19 (d, J=12.63 Hz, 1H) 8.43-8.52 (m, 2H). ESI-MS m/z [M+H]+ 449.3, ret time: 0.79 minutes.
