Tetrabutylammonium Fluoride → 1-[3-tert-butyl-1-(4-chloro-3-hydroxyphenyl)pyrazol-5-yl]-3-[(1S,4R)-4-[(3-piperidin-1-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)oxy]-1,2,3,4-tetrahydronaphthalen-1-yl]urea

Participants

Reaction Steps

To a solution of Intermediate 48a (198 mg, 0.24 mmol) in THF (4 mL) was added TBAF (1M in THF, 0.29 mL, 0.29 mmol) and the red solution was stirred at RT for 15 min. The solution was concentrated in vacuo, suspended in water (10 mL) and extracted with EtOAc (2×10 mL). The combined organics were washed with brine (10 mL), dried (Na2SO4), filtered and concentrated in vacuo. FCC, using 4-8% MeOH in DCM, gave the title compound (124 mg, 78%). LCMS (Method 5): Rt 4.50 min, m/z 655 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.27 (9H, s), 1.60-1.63 (2H, m), 1.70-1.75 (4H, m), 1.84-1.96 (2H, m), 1.99-2.13 (2H, m), 3.14 (4H, t, J=5.2 Hz), 4.82 (1H, m), 5.55 (1H, t, J 4.4), 6.33 (1H, s), 6.94 (1H, dd, J=8.5, 2.4 Hz), 7.08 (1H, d, J=8.5 Hz), 7.12 (1H, d, J=2.4 Hz), 7.16 (1H, dd, J=9.8, 2.2 Hz), 7.27-7.39 (4H, m), 7.43 (1H, d, J=8.5 Hz), 7.60-7.63 (2H, m), 8.13 (1H, s), 10.59 (1H, br s).

Provenance & Evidence