Water → 8-fluoro-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Participants

Reaction Conditions

Reaction Steps

A solution of Pd(PPh3)4 (0.077 g, 0.066 mmol), 2-fluoropyridin-3-ylboronic acid (0.19 g, 1.33 mmol), 7-bromo-8-fluoro-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (0.30 g, 0.66 mmol), and potassium carbonate (0.46 g, 3.32 mmol) in 4.5 mL dioxane was treated with 1.8 mL water and was heated to 80° C. overnight. The reaction mixture cooled to rt and diluted with EtOAc (50 mL). The layers were separated and the organics were dried over MgSO4, and concentrated in vacuo. Purification of the crude residue by column chromatography [0-80% (9:1 CH2Cl2:MeOH)/CH2Cl2] gave 8-fluoro-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (0.067 g, 0.146 mmol). Chiral separation provided (4′R)-8-fluoro-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (0.022 g, 0.048 mmol, peak 1) and (4′S)-8-fluoro-7-(2-fluoropyridin-3-yl)-3-((3-methyloxetan-3-yl)ethynyl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (0.022 g, 0.048 mmol, peak 2).

Provenance & Evidence