Tetrabutylammonium Fluoride Trihydrate → 2-Fluoropyridin 3-((3-methyloxetan-3-yl)ethynyl)-5',6'-dihydrospiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazin]-2'-amine

Participants

Reaction Conditions

Reaction Steps

In a microwave vial, tetrabutylammonium fluoride trihydrate (0.059 g, 0.187 mmol), trimethyl((3-methyloxetan-3-yl)ethynyl)silane (0.031 g, 0.187 mmol), copper(I) iodide (2.374 mg, 0.012 mmol), Pd(PPh3)4 (0.014 g, 0.012 mmol), and (S)-3-bromo-7-(2-fluoropyridin-3-yl)-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-amine (0.055 g, 0.125 mmol) were suspended in THF (1.25 mL). Argon gas was blown through the vessel, which was sealed and heated in an 80° C. oil bath for 1.5 h. The mixture was taken up in 10% MeOH-EtOAc (60 mL) and the organic layer was extracted with dilute brine (8 mL) then with saturated brine (8 mL), dried over sodium sulfate and concentrated. The residue was purified by chromatography (5% MeOH/DCM), to afford (S)-7-(2-fluoropyridin-3-((3-methyloxetan-3-yl)ethynyl)-5′,6′-dihydrospiro[chromeno[2,3-b]pyridine-5,4′-[1,3]oxazin]-2′-amine (41 mg, 0.09 mmol). MS (m/z) 457 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm: 8.32 (d, 1H, J=2.0 Hz), 8.20 (d, 1H, J=4.9 Hz), 7.90 (m, 1H), 7.78 (s, 1H), 7.53 (m, 2H), 7.38 (d, 1H, J=8.4 Hz), 7.27 (m, 1H), 4.94 (d, 2H, J=5.3 Hz), 4.50 (d, 2H, J=5.5 Hz), 4.44 (br, 2H), 4.28 (m, 2H), 1.95 (m, 1H), 1.85 (m, 1H), 1.74 (s, 3H).

Provenance & Evidence