Potassium Carbonate → (S)-3-bromo-7-(4-fluoropyridin-3-yl)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-thiazol]-2'-amine

Participants

Reaction Conditions

Reaction Steps

A pressure reaction vessel was charged with (S)-3-bromo-7-iodo-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (1.2 g, 2.53 mmol, prepared as described in Method BB26), potassium carbonate (1.75 g, 12.66 mmol), 4-fluoropyridin-3-ylboronic acid (0.71 g, 5.06 mmol), tetrakis(triphenylphosphine)palladium(0) (0.29 g, 0.25 mmol), dioxane (16.87 mL) and water (8.44 mL). The reaction was stirred and heated at 100° C. for 45 min. After cooling for rt, LCMS showed about 50% conversion. More Pd(PPh3)4 (30 mg) and 4-fluoropyridin-3-ylboronic acid (300 mg) were added and reaction was heated at 100° C. for another 30 min. After cooling for rt, the organic layer was separated with a separatory funnel, dried over sodium sulfate, filtered, and concentrated to afford yellow oil which was purified with reverse phase HPLC. Fractions containing product were concentrated and saturated aq. NaHCO3 (25 mL) was added. A white solid precipitated out of solution which was filtered off and dried to afford a white solid, (S)-3-bromo-7-(4-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-thiazol]-2′-amine (0.51 g, 1.15 mmol, 46% yield). MS m/z=443.0 [M+H]+. Calc'd for C19H12BrFN4OS: 441.99.

Provenance & Evidence