Acetone → HCID 178460521, compound

Participants

Reaction Steps

A suspension of 3-chloro-N-((3-chloro-5-fluorophenyl)carbamothioyl)benzamide (75 g, 219 mmol) in tert-butyl methyl ether (TBME) (1.1 L) was heated to 50° C. Next, 5-(trifluoromethyl)-1H-pyrazol-3-amine (39.6 g, 262 mmol, 1.20 equiv) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) (64.2 g, 328 mmol, 1.50 equiv) were added. The resulting reaction mixture was stirred at 50° C. for 1 hour and diluted with EtOAc (1.0 L) and water (1.0 L). The organic extract was washed with a saturated, aqueous sodium chloride solution (0.5 L), dried (Na2SO4), filtered, and concentrated. The resulting residue was diluted with EtOAc (300 mL) and this mixture was warmed to 50° C., then filtered through Celite. Next, the filtrate was concentrated to approximately 75 mL and slowly diluted with hexanes (750 mL). The resulting mixture was stirred at room temperature for 1 hour and filtered. The resulting solid was heated in acetone (100 mL), filtered, diluted with hexanes (100 mL), and the resulting mixture was heated until a clear solution developed. Next, the mixture was further diluted with hexanes (300 mL) and stirred at room temperature overnight. The resulting solids were collected by filtration, rinsed with hexanes (100 mL) and dried in vacuo at room temperature to afford (25.1 g, 25% yield) of crystalline 3-chloro-N-(((3-chloro-5-fluorophenyl)amino)((5-(trifluoromethyl)-1H-pyrazol-3-yl)amino)methylene)benzamide acetone solvate. 1H NMR analysis indicates that the molar ratio of 3-chloro-N-(((3-chloro-5-fluorophenyl)amino)((5-(trifluoromethyl)-1H-pyrazol-3-yl)amino)methylene)benzamide to acetone is 3 to 2. 1H NMR (DMSO-d6) of the title compound: δ 13.3 (s, 1H), 10.7 (s, 1H), 10.0 (s, 1H), 7.90 (s, 1H), 7.82 (d, 1H, J=7.6), 7.69 (d, 1H, J=8.4), 7.58 (m, 2H), 7.07 (d, 1H, J=8.4), 6.03 (s, 1H), 2.05 (s, 4H, Acetone). HPLC: 97.6% purity at 26.08 min.

Provenance & Evidence