Reaction Steps
To a stirred mixture of 3-methyl-5-(2-oxo-3-(4-(trifluoromethyl)benzyl)-imidazolidin-1-yl)thiophene-2-carboxylic acid (3.68 g, 9.56 mmol), 1-hydroxybenzotriazole (1.94 g, 14.36 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (2.75 g, 14.3 mmol) in N,N-dimethylformamide (40 mL) was added N,N-diisopropylethylamine (5.00 mL, 5.00 mmol), followed by the addition of 3-(aminomethyl)pyridine (0.97 mL, 9.57 mmol). The resulting reaction mixture was stirred for 16 h, then was diluted with ethyl acetate (300 mL). The organic layer was washed with saturated aqueous sodium bicarbonate solution (3×100 mL), water (100 mL) and brine (100 mL). The combined water/brine layer was extracted with dichloromethane (200 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by recrystallization from 50% ethyl acetate in hexanes to afford the title compound as a colorless solid (2.48 g, 55%): mp 102-104° C. (hexanes/ethyl acetate); 1H NMR (300 MHz, CDCl3) δ 8.59 (s, 1H), 8.52 (s, 1H), 7.69 (d, J=7.8 Hz, 1H), 7.60 (d, J=8.0 Hz, 2H), 7.40 (d, J=8.0 Hz, 2H), 7.29-7.22 (m, 1H), 6.20 (t, J=5.6 Hz, 1H), 6.10 (s, 1H), 4.58 (d, J=5.6 Hz, 2H), 4.50 (s, 2H), 3.85-3.77 (m, 2H), 3.50-3.42 (m, 2H), 2.48 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 163.5, 155.8, 149.1, 148.7, 142.3, 141.4, 140.1, 135.5, 134.2, 130.1 (d, JC-F=32.6 Hz), 128.4, 125.7 (q, JC-F=3.8 Hz), 123.5, 122.1, 119.2, 112.5, 47.7, 42.7, 41.6, 41.1, 16.0; MS (ES+) m/z 475.3 (M+1).
