Dimethylformamide → (S)-7-(cyclopropylethynyl)-3-(2-fluoro-2-methylpropoxy)-5'H-spiro[chromeno[2,3-b]pyridine-5,4'-oxazol]-2'-amine

Participants

Reaction Conditions

Reaction Steps

A sealable tube was charged with (S)-7-bromo-3-(2-fluoro-2-methylpropoxy)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine (75 mg, 0.178 mmol), copper(i) iodide (3.38 mg, 0.018 mmol), tetrakis(triphenylphosphine)palladium (20.53 mg, 0.018 mmol). Added DMF (355 μL, 0.178 mmol), diisopropylamine (498 μL, 3.55 mmol) and cyclopropylacetylene (75 μL, 0.888 mmol) and the tube was flushed with argon, sealed and heated to 110° C. for 2 hours. More copper iodide (3.38 mg, 0.018 mmol), tetrakis(triphenylphosphine)palladium (20.53 mg, 0.018 mmol), diisopropylamine (498 μL, 3.55 mmol) and cyclopropylacetylene (75 μL, 0.888 mmol) were added and the black mixture was heated at 110° C. for 3 hours. The reaction was diluted with water (100 mL) and poured into a separatory funnel containing ethyl acetate (50 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water and then brine, dried over sodium sulfate, filtered and concentrated in vacuo to provide a brown oil that was purified by silica gel chromatography (Redi-Sep pre-packed silica gel column (12 g), 0-10% methanol in methylenechloride with 0.1% ammonium hydroxide) to provide (S)-7-(cyclopropylethynyl)-3-(2-fluoro-2-methylpropoxy)-5′H-spiro[chromeno[2,3-b]pyridine-5,4′-oxazol]-2′-amine as a tan solid.

Provenance & Evidence