Diisopropylethylamine → Methyl 3-amino-6-(2,6-difluorophenyl)-5-fluoropicolinate

温度

100 °C

To a screw-cap vial equipped with a magnetic stir bar, methyl 3-amino-6-bromo-5-fluoropyridine-2-carboxylate (99.6 mg, 0.400 mmol) was added, followed by 2-(2,6-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Combi-Blocks, 190 mg, 0.80 mmol), and bis(tri-tert-butylphosphine)palladium (40.9 mg, 0.080 mmol). The vial was sealed with a PTFE-lined septum, evacuated and backfilled with nitrogen three times. 1,4-Dioxane (2.0 mL) was added via a syringe, followed by DIPEA (0.14 mL, 0.80 mmol) and deoxygenated water (0.05 mL). The mixture was heated at 100° C. for 2 h. After cooling to room temperature, the mixture was diluted with EtOAc (40 mL) and washed with water (40 mL) and brine (40 mL), then dried over Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by chromatography on silica gel (0-50% EtOAc in hexanes) to give the sub-title compound as a white solid (84.0 mg, 74%). LCMS calc. for C13H10F3N2O2(M+H)+: m/z=283.1. found 283.1.

1. customTo a screw-cap vial equipped with a magnetic stir bar
2. customevacuated
3. addition1,4-Dioxane (2.0 mL) was added via a syringe
4. customdeoxygenated water (0.05 mL)
5. temperatureAfter cooling to room temperature
6. additionthe mixture was diluted with EtOAc (40 mL)
7. washwashed with water (40 mL) and brine (40 mL)
8. dry with materialdried over Na2SO4
9. concentrationconcentrated under reduced pressure
10. customThe resulting residue was purified by chromatography on silica gel (0-50% EtOAc in hexanes)

ORDレコード

ord-fe373c2017ba4db18de1332bab3cdb25

出典データセット

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09200004B2