反应详情

5-(2-Azabicyclo[2.2.2]oct-5-en-5-yl)-1-[(2,2-difluorocyclopropyl)-methyl]-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (6-3, 40 mg, 0.12 mmol, 1.0 equiv), isoxazole-3-carboxylic acid (2-6, 21 mg, 0.18 mmol, 1.5 equiv), DIPEA (64 μL, 0.36 mmol, 3.0 equiv) and HATU (69 mg, 0.18 mmol, 1.5 equiv) were added to anhydrous 1,4-dioxane (12 mL). After stirring for 10 min at room temperature, LCMS showed consumption of starting material. Purification by reverse-phase HPLC (20-100% CH3CN:0.1% TFA in H2O) provided 2-7 as a white solid. MS m/z (M+H): calculated=442.1685; observed=442.1682. 1H NMR δ (ppm)(CHCl3-d): 8.41 (1H, dd, J=27.39, 1.68 Hz), 7.26-7.21 (1H, m), 7.18 (1H, dd, J=8.10, 1.54 Hz), 6.99 (1H, ddd, J=22.62, 6.35, 2.02 Hz), 6.70 (1H, dd, J=12.85, 1.68 Hz), 5.56-5.52 (0.4H, m), 5.41 (0.6H, m), 4.24-4.16 (1H, m), 3.95 (0.4H, dd, J=11.04, 2.28 Hz), 3.90-3.84 (1H, m), 3.75 (1H, dd, J=15.06, 7.88 Hz), 3.62 (0.6H, dd, J=12.35, 2.29 Hz), 3.58-3.52 (0.4H, m), 3.48 (3H, d, J=3.78 Hz), 3.36 (0.6H, d, J=12.38 Hz), 2.22-2.11 (1H, m), 2.05-1.9 (1H, m), 1.91-1.80 (1H, m), 1.61-1.46 (3H, m), 1.29-1.24 (1H, m). (Mixture of rotamers at RT)

1. customconsumption of starting material
2. customPurification by reverse-phase HPLC (20-100% CH3CN:0.1% TFA in H2O)