Dimethylformamide → (4S)-3'-(3,3-dimethylbut-1-ynyl)-7'-(2-fluoro-3-pyridinyl)spiro[5H-1,3-oxazole-4,5'-chromeno[2,3-b]pyridine]-2-amine

Participants

Reaction Conditions

Reaction Steps

Combined (S)-3-bromo-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (80 mg, 0.187 mmol), tetrakis(triphenylphosphine)palladium (21.64 mg, 0.019 mmol), copper(i) iodide (3.57 mg, 0.019 mmol) and THF (749 μL, 0.187 mmol) and DMF (749 μL, 0.187 mmol) in a reaction tube. Added DIPA (525 μL, 3.75 mmol) then 3,3-dimethylbut-1-yne (115 μL, 0.936 mmol) and flushed the reaction tube with argon. Sealed and heated at 110° C. for 3 hours. The mixture was partioned between water (10 mL) and EtOAc (10 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (2×10 mL). The combined organic extracts were dried over sodium sulfate, filtered, and evaporated. The residue was purified by chromatography on a 25-g SNAP column, eluting with 0-70% of a 90:10:1 mixture of DCM/MeOH/NH4OH in DCM. The derived residue was then purified by reverse-phase HPLC (10-90% CH3CN/H2O with 0.1% TFA) to give (S)-3-(3,3-dimethylbut-1-ynyl)-7-(2-fluoropyridin-3-yl)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a white powder after evaporation from DCM/hexane. Found MS: MH+=429.

Provenance & Evidence