Water → 1-[5-tert-Butyl-2-(4-cyano-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4S)-4-(3-isopropyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea

Participants

Reaction Steps

A solution of Intermediate 14b (61.6 mg, 0.148 mmol), Intermediate 5c (43.4 mg, 0.135 mmol), and DIPEA (0.029 mL, 0.169 mmol) in dioxane-DMF (3:1, 2.0 mL) was stirred at 60° C. for 18 h. Water (3 mL) was added, then the mixture extracted with DCM-MeOH (9:1, 2×3 mL). The combined organics were passed through a hydrophobic frit and concentrated in vacuo to leave an orange oil. FCC, using 2-8% MeOH in DCM, gave the title compound as a white solid after freeze-drying (35.0 mg, 44%). LCMS (Method 5): Rt 4.46 min, m/z 589 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.28 (9H, s), 1.37 (3H, d, J 7.1), 1.39 (3H, d, J 7.1), 1.75 (1H, m), 2.01 (1H, m), 2.09-2.22 (2H, m), 3.57 (1H, sept, J 6.9), 4.88 (1H, m), 5.58 (1H, t, J 4.5), 6.38 (1H, s), 7.06 (1H, d, J 8.2), 7.23 (1H, dd, J 9.9, 2.2), 7.27 (1H, d, J 7.3), 7.29-7.38 (2H, m), 7.42 (1H, d, J 7.5), 7.69 (1H, dd, J 9.9, 0.9), 7.75 (2H, d, J 8.9), 7.96 (2H, d, J 8.7), 8.21 (2H, s).

Provenance & Evidence