Ammonium Chloride → 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxamide

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Reaction Steps

To a solution of 2-(1-(4-fluorobenzyl)-5-oxo-1H-1,2,4-triazol-4(5H)-yl)-4-methylthiazole-5-carboxylic acid (0.35 g, 1.05 mmol) in anhydrous N,N-dimethylformamide (10.0 mL) was added 1-hydroxybenzotriazole (0.28 g, 2.09 mmol), 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) (0.80 g, 2.09 mmol), N,N-diisopropylethylamine (1.09 mL, 6.28 mmol) and ammonium chloride (0.22 g, 4.19 mmol). The resulting solution was stirred at ambient temperature for 72 h and concentrated in vacuo. The residue was suspended in saturated aqueous sodium bicarbonate solution (100 mL). The crude product was filtered and washed with water (50 mL). The crude solid was recrystallized in ethanol to afford the title compound as an off-white solid (0.27 g, 73%): mp 232-233° C.; 1H NMR (300 MHz, DMSO-d6) δ 8.75 (s, 1H), 7.64 (br, 2H), 7.40-7.36 (m, 2H), 7.22-7.16 (m, 2H), 5.00 (s, 2H), 2.55 (s, 3H); 13C NMR (75 MHz, DMSO-d6) δ 162.7, 161.69 (d, 1JC-F=243.5 Hz), 151.3, 150.9, 149.7, 132.2 (d, 4JC-F=3.0 Hz), 132.0, 129.9 (d, 3JC-F=8.4 Hz), 123.0, 115.4 (d, 2JC-F=21.5 Hz), 47.7, 16.8; MS (ES+) m/z 334.3 (M+1).

Provenance & Evidence