Tetrabutylammonium Fluoride Trihydrate → 5',6'-Dihydrospiro[chromeno[2,3-b]pyridine-5,4'-[1,3]oxazin]-2'-amine

Temperature

80 °C

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-yl)-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, 1 H, J=2.0 Hz), 8.20 (d, 1 H, J=4.9 Hz), 7.90 (m, 1 H), 7.78 (s, 1 H), 7.53 (m, 2 H), 7.38 (d, 1 H, J=8.4 Hz), 7.27 (m, 1 H), 4.94 (d, 2 H, J=5.3 Hz), 4.50 (d, 2 H, J=5.5 Hz), 4.44 (br, 2 H), 4.28 (m, 2 H), 1.95 (m, 1 H), 1.85 (m, 1 H), 1.74 (s, 3 H).

1. customwas sealed
2. extractionthe organic layer was extracted with dilute brine (8 mL)
3. dry with materialwith saturated brine (8 mL), dried over sodium sulfate
4. concentrationconcentrated
5. customThe residue was purified by chromatography (5% MeOH/DCM)

ORD record

ord-970dc890908d4f62b512ad57c96d51a5

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012446B2