Hydrochloric Acid → HCID 178462759, compound

Participants

Reaction Steps

Combined 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (100 mg, 0.312 mmol), 1H-benzo[d][1,2,3]triazol-1-ol (50.6 mg, 0.375 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (71.8 mg, 0.375 mmol), DMF (Volume: 624 μl), and N-ethyl-N-isopropylpropan-2-amine (273 μl, 1.561 mmol). The solution was stirred at ambient temperature for 5 minutes then (R)-1-ethyl-3-methylpiperazine dihydrochloride (69.1 mg, 0.343 mmol) was added. The reaction was stirred at ambient temperature for 12 h. The reaction was diluted with a pre-made solution of water:ethanol (1:1, 10 mL). The reaction was acidified to pH 5 using 1N HCl and 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 collected and dried under vacuum to give the title compound (67.7 mg, 0.157 mmol, 50.4% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.01 (s, 3 H) 1.21-1.37 (m, 3 H) 1.92-2.06 (m, 1 H) 2.09-2.21 (m, 1 H) 2.42 (s, 5 H) 2.67-2.99 (m, 2 H) 3.05-4.61 (m, 3 H) 7.61 (dd, J=8.08, 1.52 Hz, 1 H) 7.68 (s, 1 H) 7.86 (d, J=8.08 Hz, 1 H) 8.00 (dd, J=8.59, 2.27 Hz, 1 H) 8.08 (s, 1 H) 8.40 (d, J=8.59 Hz, 1 H) 8.49 (d, J=2.27 Hz, 1 H). ESI-MS m/z [M+H]+ 431.3, ret time: 0.80 minutes.

Provenance & Evidence