Cesium carbonate → Methyl 3-[(4-fluorobenzyl)amino]pyridine-4-carboxylate

Temperature

116 °C

Methyl 3-bromoisonicotinate (220 mg, 1.02 mmol), 4-fluorobenzylamine (132 μL, 1.22 mmol), tris(dibenzylideneacetone)dipalladium(0) (47 mg, 0.051 mmol), Xantphos (89 mg, 0.153 mmol), and cesium carbonate (500 mg, 1.53 mmol) were combined in dioxane (4 mL) under N2 in a sealed microwave tube. The reaction mixture was heated at 116° C. in a microwave for 1 h. The mixture was then filtered, washing with DCM, to remove solids. The solution was concentrated in vacuo and purified by silica gel chromatography (20-50% EtOAc/hexanes) to give 228 mg (88%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.18 (s, 1H), 7.93 (d, 1H, J=5.0 Hz), 7.79 (br s, 1H), 7.63 (d, 1H, J=5.0 Hz), 7.27-7.34 (m, 2H), 7.03 (t, 2H, J=8.6 Hz), 4.47 (d, 2H, J=5.6 Hz), 3.89 (s, 3H). [M+H] calc'd for C14HDFN2O2, 261; found 261.

1. filtrationThe mixture was then filtered
2. washwashing with DCM
3. customto remove solids
4. concentrationThe solution was concentrated in vacuo
5. custompurified by silica gel chromatography (20-50% EtOAc/hexanes)

ORD record

ord-9068797d99f34fe48228d7d67576a9c7

Source dataset

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09085534B2