Dichloromethane → 5-(2,4-Dichloro-benzoylamino)-1-phenyl-1H-pyrazole-4-carboxylic acid (4-chloro-phenyl)-amide

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Reaction Steps

To a solution of 4-bromoaniline (1, 60.0 mg, 0.35 mmol) in dichloromethane (1.5 mL) is added p-toluoyl chloride (2, 46.1 μL, 0.35 mmol) and TEA (97.2 μL, 0.70 mmol). The reaction mixture is stirred at room temperature for 30 minutes to provide N-(4-bromo-phenyl)-4-methylbenzamide (3). After removal of the solvent, without further purification, 3 is taken by thionyl chloride (0.5 mL) and the mixture is heated at 80° C. for 1 hour before thionyl chloride is removed in vacuo to provide imidoyl chloride 4. Without further purification, the crude 4 is dissolved in dichloroethane (1.0 mL), and ethyl 5-amino-1-phenyl-4-pyrazole-carboxylate (5, 96.8 mg, 0.42 mmol) and TiCl4 (153.0 μL, 1.40 mmol) are added. The reaction mixture is heated at 160° C. in a microwave for 20 minutes, cooled down, diluted with dichloroethane (5 mL), and quenched with H2O (5 mL). The two layers are separated. The aqueous layer is extracted with dichloroethane. The combined dichloroethane layer is washed with brine, dried over MgSO4, concentrated, and purified by silica gel chromatography followed by reverse phase HPLC to provide 5-(4-bromo-phenyl)-1-phenyl-6-p-tolyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one as a white solid product: 1H NMR (CDCl3, 400 MHz) δ 8.31 (s, 1H), 8.16 (d, 2H), 7.50 (t, 2H), 7.47 (d, 2H), 7.34 (t, 1H), 7.22 (d, 2H), 7.06 (d, 2H), 7.02 (d, 2H), 2.32 (s, 3H); HPLC-MS calculated for C24H17BrN4O(M+H+) 457.1. Found: 457.1.

Provenance & Evidence