1H-1,2,4-Triazole → {1-[4-(4-oxo-2-phenyl-8-[1,2,4]triazol-4-yl-4H-pyrano[2,3-c]pyridin-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a microwave vial were added {1-[4-(8-chloro-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (6.7 mg, 0.0133 mmol), 1,2,4-triazole (4.6 mg, 0.067 mmol), cesium carbonate (8.7 mg, 0.0266 mmol), copper(I) iodide (0.8 mg, 0.004 mmol) and NMP (0.5 mL). The reaction mixture was heated in a microwave reactor at 150° C. for 30 minutes. The reaction was repeated with {1-[4-(8-chloro-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (20 mg, 0.04 mmol), 1,2,4-triazole (13.8 mg, 0.2 mmol), cesium carbonate (26.1 mg, 0.08 mmol), copper(I) iodide (2.4 mg, 0.012 mmol) and NMP (0.7 mL). The reaction mixtures were combined and partitioned between EtOAc and water. The organic phase was extracted further with EtOAc and the combined organic extracts were washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 50 to 75% EtOAc in cyclohexane) to afford the title compound (13.2 mg, 46%) as a colourless gum. LCMS (Method H): RT=3.84 min, [M+H]+=536.

Provenance & Evidence