Cesium carbonate → 4-(Bromomethyl)-2-methoxypyridine

Temperature

80 °C

To a solution of the above compound (0.060 g, 0.14 mmol) in a mixture of 1 mL of THF and 0.15 mL of water under an atmosphere of nitrogen was added 4-(bromomethyl)-2-methoxypyridine hydrobromide (0.048 g, 0.17 mmol), cesium carbonate (0.156 g, 4.80 mmol), and [1,1′-bis-(diphenyl-phosphino)-ferrocene]dichloro-palladium(II), 1:1 complex with dichloromethane (5.0 mg, 0.69 mmol). The mixture was heated at 80° C. for 3 h, cooled to rt, and diluted with dichloromethane. The organic solution was washed with water, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 433.2231 for [M+H]+[Calc'd for C23H29N4O3, [M+H]+=433.2234]. 1H NMR (400 MHz, CDCl3) δ 8.91-8.89 (m, 1H), 8.09-8.06 (m, 1H), 7.99-7.97 (m, 2H), 7.37 (dd, J=8.5 Hz, 4.1 Hz, 1H), 6.65 (d, J=5.2 Hz), 6.42 (s, 1H), 4.74-4.60 (m, 2H), 4.37-4.31 (m, 1H), 4.24 (s, 2H), 3.83 (s, 3H), 3.62-3.57 (m, 1H) 3.25 (s, 3H), 2.32-2.30 (m, 1H), 2.18-2.00 (m, 1H), 1.89-1.86 (m, 1H), 1.81-1.74 (m, 2H), 1.59-1.53 (m, 1H), 1.46-1.20 (m, 2H).

1. temperaturecooled to rt
2. washThe organic solution was washed with water
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customThe residue was purified via silica gel chromatography
7. washeluting with 0-5% methanol in dichloromethane

ORD record

ord-176ca0882d7a41cba66ea45cfc7fd04e

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09284312B2