Tetrabutylammonium Fluoride → 1-[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-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

To a solution of Intermediate 10d (100 mg, 0.15 mmol) in THF (2 mL), TBAF (1M in THF, 0.23 mL, 0.23 mmol) was added at RT and stirred for 10 min. The reaction mixture was diluted with H2O (5 mL) and DCM (5 mL). The layers were separated, and aqueous layer was extracted with DCM (3×5 mL). The combined organic layers were dried (MgSO4), filtered, concentrated in vacuo and then purified by FCC using 0-5% [2M NH3 in MeOH] in DCM). The residue was washed with water and purified by HPLC (30%-100% MeCN in H2O, 0.1% formic acid) to give the title compound as a white powder (47 mg, 57%). Rf=0.2 (5% [2M NH3 in MeOH] in DCM) LCMS (Method 5): Rt 3.59 min, m/z 532 [MH+]. 1H NMR (400 MHz, CDCl3): 1H NMR (300 MHz, CDCl3): 1.25 (s, 9H), 1.43 (d, J=6.9 Hz, 3H), 1.46 (d, J=6.9 Hz, 3H), 1.92-2.30 (m, 4H), 3.25 (p, J=6.9 Hz, 1H), 3.95 (t, J=4.7 Hz, 2H), 4.15 (dd, J=5.3, 3.5 Hz, 2H), 5.09-5.16 (m, 1H), 5.92 (d, J=8.0 Hz, 1H), 6.12 (s, 1H), 6.92 (dd, J=9.8, 1.9 Hz, 1H), 7.22-7.27 (m, 2H), 7.33 (td, J=5.8, 3.0 Hz, 1H), 7.40 (s, 1H), 7.43 (br s, 2H), 7.47 (d, J=7.8 Hz, 1H), 7.70 (s, 1H).

Provenance & Evidence