Reaction Steps
2,5-Dimethyl-1-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (3-hydroxy-phenyl)-amide, previously described in Example 2C, was prepared as a white solid (0.92 g, 80%). 1H-NMR (DMSO-d6): δ 9.15 (1H, s), 9.13 (1H, s), 7.86 (1H, d, J=7.8), 7.77 (1H, t, J=7.3), 7.66 (1H, t, J=7.8), 7.35 (1H, d, J=7.8), 7.20 (1H, t, J=2.0), 6.98 (1H, d, J=8.3), 6.91 (1H, t, J=7.8), 6.47 (1H, s), 6.29 (1H, d, J=7.8), 1.98 (3H, s), 1.73 (3H, s); MS (ESI): 375 (MH+). Into an oven-dried 1 dram vial was added 2,5-dimethyl-1-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (3-hydroxy-phenyl)-amide (50 mg, 133 μmol), K2CO3 (22 mg, 160 μmol), 1-bromomethyl-4-fluoro-benzene (28 mg, 146 μmol) and 0.5 mL DMF. The vial was sealed and stirred 1 h at room temperature. The crude material was purified by reverse-phase chromatography (C18 column), eluting with 0.05% TFA in MeCN/H2O (30:70 to 90:10) to yield the title compound (19 mg, 30%) as an off-white solid. 1H-NMR (DMSO-d6): δ 9.43 (1H, s), 8.00 (1H, d, J=7.8), 7.90 (1H, t, J=7.8), 7.80 (1H, t, J=7.3), 7.58 (1H, m), 7.50 (3H, m), 7.35 (1H, d, J=8.6), 7.22 (3H, m), 6.69 (1H, d, J=8.3), 6.63 (1H, s), 5.07 (2H, s), 2.14 (3H, s), 1.88 (3H, s); MS (ESI): 483 (MH+). B. The following compounds were prepared in a similar manner described in 25A using the appropriate alkyl bromides:
