Diisopropylethylamine → 1-(5-tert-Butyl-2-(3-hydroxy-propyl)-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(2,6-dichlorophenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydronaphthalen-1-yl]-urea

Participants

Reaction Conditions

Reaction Steps

A mixture of Intermediate 35b (200 mg, 0.54 mmol), Intermediate 26d (228 mg, 0.54 mmol), and DIPEA (140 μL, 0.80 mmol) in dioxane (2 mL) was stirred at 70° C. for 18 h. The reaction mixture was cooled to RT, diluted with DCM (10 mL), and washed with water (2×10 mL). The aqueous layer was extracted with DCM, and the combined organics were passed through a phase separator and concentrated in vacuo and the resultant residue was purified by FCC, using 0-5% [2M NH3 in MeOH] in DCM to afford the title compound (270 mg, 76%). A 50 mg sample of this was purified by MDAP (Method 7) to afford the title compound as a glassy solid (17 mg). LCMS (Method 5): Rt 4.24 min, m/z 648.4 [MH+]. 1H NMR (400 MHz, d6-DMSO): 1.20 (9H, s), 1.79-1.87 (2H, m), 1.88-2.14 (4H, m), 3.41 (2H, t, J=5.9 Hz), 3.91 (2H, t, J=7.2 Hz), 4.58 (1H, br s), 4.79-4.87 (1H, m), 5.55 (1H, t, J=4.2 Hz), 6.03 (1H, s), 6.93 (1H, d, J=8.8 Hz), 7.23-7.29 (1H, m), 7.32-7.38 (4H, m), 7.69-7.79 (3H, m), 7.91 (1H, dd, J=9.6 Hz, 0.9 Hz), 7.98 (1H, d, J=1.7 Hz), 8.17 (1H, s).

Provenance & Evidence