Diisopropylethylamine → N-(3-(4-chloro-1-methyl-1H-pyrazol-5-yl)-4-hydroxyphenyl)-2-fluoro-4-methoxybenzamide

Participants

Reaction Steps

4-Amino-2-(4-chloro-1-methyl-1H-pyrazol-5-yl)phenol (2.0 g, 8.94 mmol) was suspended in anhydrous CH2Cl2 (75 mL). The suspension was made to dissolve by the adding anhydrous DMF (5 mL) and briefly heating the solution using a heat gun (˜50° C.). 2-Fluoro-4-methoxybenzoic acid (1.52 g, 8.94 mmol), DIEA (2.34 mL, 13.4 mmol) and HATU (4.08 g, 10.7 mmol) were added to the solution. The reaction was stirred at room temperature for 2 hours. After this time, the reaction was extracted (120 mL each of H2O/CH2Cl2). The aqueous layer was extracted once more with CH2Cl2 (120 mL). The combined organic layer was dried over MgSO4, filtered, and concentrated. The product was purified by column chromatography (0,20,40,50,70% EtOAc/Hexanes) to yield N-(3-(4-chloro-1-methyl-1H-pyrazol-5-yl)-4-hydroxyphenyl)-2-fluoro-4-methoxybenzamide (2.88 g, 7.66 mmol, 77.1%) as a colorless oil that turned solid upon standing. LCMS m/z 376.1 (M+H); 1H NMR (400 MHz, MeOH-d4) δ ppm 3.76 (s, 3 H), 3.90 (s, 3 H), 6.87 (dd, J=33.09, 2.53 Hz, 1 H), 6.87 (dd, J=11.49, 2.40 Hz, 1H), 7.00 (d, J=8.59 Hz, 1 H), 7.54 (s, 1 H), 7.55 (d, J=2.53 Hz, 1 H), 7.66 (dd, J=8.84, 2.53 Hz, 1 H), 7.76 (t, J=8.72 Hz, 1 H).

Provenance & Evidence