Diisopropylethylamine → (2R,3 S,5R)-5-((6-chloro-5-((4-(2-hydroxypropan-2-yl)phenyl)ethynyl)-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol

Participants

Reaction Steps

A mixture of (2R,3 S,5R)-5-((6-chloro-5-iodo-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol (50 mg, 0.120 mmol), 2-(4-ethynylphenyl)propan-2-ol (28.2 mg, 0.176 mmol), Pd(Ph3P)4 (13.58 mg, 0.012 mmol), copper(I) iodide (2.237 mg, 0.012 mmol) and diisopropylethylamine (0.062 ml, 0.360 mmol) in dioxane (2 ml) was charged in a reaction tube. Then the tube was sealed and N2 was bubbled through for 5 min. The mixture was heated at 80 C for 2 h, and then concentrated. The resulting residue was purified on reverse phase HPLC eluting with 10-70% CH3CN/H2O with TFA as an additive to give the title compound. LC-MS m/e=458.35 (M+H)+ (Rt 1.70/4.0 min); 1H NMR δ (ppm) (CD3OD): 7.83 (s, 1H), 7.58-7.54 (m, 4H), 5.13 (septet, 1H, J=5 Hz)), 4.34 (ddd 1H, J=12, 5, 2 Hz), 3.89 (dd, 1H, J=12, 2 Hz), 3.64 (dd, 1H, J=12, 6 Hz)), 3.61 (dd, 1H, J=12, 5 Hz), 3.37 (t, 1H, J=11 Hz), 3.19-3.15 (m, 1H), 2.77-2.73 (m, 1H), 1.70 (dd, 1H, J=23, 12 Hz), 1.55 (s, 6H).

Provenance & Evidence