反应详情

5-(2-Azabicyclo[2.2.2]oct-5-en-5-yl)-1-(2,2-dimethylpropyl)-3-methyl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (2-5, 291 mg, 0.90 mmol, 1.0 equiv), isoxazole-3-carboxylic acid (2-6, 151 mg, 1.4 mmol, 1.5 equiv), DIPEA (0.47 mL, 2.7 mmol, 3.0 equiv) and HATU (510 mg, 1.4 mmol, 1.5 equiv) were added to anhydrous 1,4-dioxane (9 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=422.2187; observed=422.2189. 1H NMR δ (ppm)(CHCl3-d): 8.40 (1H, dd, J=27.77, 1.66 Hz), 7.22-7.17 (1H, m), 7.12 (1H, dd, J=8.11, 1.50 Hz), 6.97 (1H, m), 6.70 (1H, dd, J=11.92, 1.66 Hz), 5.55-5.52 (0.4H, m), 5.42-5.38 (0.6H, m), 3.95 (0.4H, m), 3.88 (1H, m), 3.62 (2.6H, m), 3.53 (0.4H, m), 3.47 (3H, d, J=3.86 Hz), 3.36 (0.6H, d, J=12.39 Hz), 2.21-2.11 (1H, m), 1.91-1.80 (1H, m), 1.61-1.52 (2H, m) 0.99 (9H, d, J=1.91 Hz). (Mixture of rotamers at RT).

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