Cesium carbonate → N-(5-((2-(3,3-dimethylureido)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of Example C1 (0.150 g, 0.359 mmol), N,N-dimethyl urea (0.190 g, 2.154 mmol), Cs2CO3 (0.292 g, 0.897 mmol) and Xantphos (0.062 g, 0.108 mmol) in dioxane (7 mL) was sparged with Ar, treated Pd2(dba)3 (0.043 g, 0.047 mmol), sparged again with Ar and heated at 100° C. overnight. The mixture was cooled to RT, treated with aqueous saturated NaHCO3, and extracted with EtOAc (3×). The combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM). The yellowish solid was re-purified via reverse-phase chromatography (MeCN/H2O with 0.1% TFA). The organics were removed under reduced pressure, the aqueous residue neutralized with satd. NaHCO3 and extracted with EtOAc (3×). The combined organics were dried over Na2SO4, concentrated to dryness and dried in vacuo. The residue was dissolved in 4:1 MeCN/water, frozen and lyophilized overnight to afford N-(5-((2-(3,3-dimethylureido)pyridin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (110 mg, 54%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 10.96 (s, 1 H), 8.90 (s, 1 H), 8.20 (d, J=2.5 Hz, 1 H), 8.10 (J=5.7 Hz, 1 H), 8.06 (d, J=9.0 Hz, 1 H), 7.69 (dd, J=9.0, 2.9 Hz, 1 H), 7.37 (d, J=2.4 Hz, 1 H), 6.60 (dd, J=5.7, 2.4 Hz, 1 H), 3.93-3.77 (m, 5 H), 3.47-3.35 (m, 4 H), 2.87 (s, 6 H), 1.76-1.65 (m, 2 H), 1.62-1.56 (m, 2H); MS (ESI) m/z: 470.2 (M+H+).

Provenance & Evidence