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

Participants

Reaction Conditions

Reaction Steps

2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)propan-1-ol (61.3 mg, 0.220 mmol), (2R,3S,5R)-5-((6-chloro-5-iodo-1H-imidazo[4,5-b]pyridin-2-yl)oxy)-2-(hydroxymethyl)tetrahydro-2H-pyran-3-ol (75 mg, 0.176 mmol) and potassium phosphate tribasic (150 mg, 0.70 mmol) were dissolved in dioxane (600 μl) and water (600 μl). The mixture was sparged with N2 with for 15 min and [1,1′-Bis(Diphenyl-phosphino)Ferrocene]Dichloropalladium(II) (25.8 mg, 0.035 mmol) was added. The reaction was stirred 3 h at 80° C., then diluted with water and EtOAc. The aqueous phase was extracted with EtOAc (×2), and the combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by mass directed reverse phase HPLC eluted with acetonitrile in water containing 0.1% formic acid. The desired fractions were combined and lyophilized to give the title compound as a white solid. LC-MS: calculated for C21H24ClN3O6 449.14 observed m/e: 449.92 (M+H)+ (Rt 1.03/2 min); 1H NMR δ (ppm) (CD3OD): 7.77 (s, 1H), 7.58 (d, 2H), 7.02 (d, 2H), 5.10 (septet, 1H), 4.57-4.54 (m, 2H), 4.32 (dd, 1H), 3.88 (d, 1H), 3.73-3.59 (m, 3H), 3.36 (t, 1H), 3.17-3.14 (m, 1H), 2.75-2.73 (m, 1H), 1.67 (dd, 1H), 1.31 (d, 3H).

Provenance & Evidence