Toluene → 6-[2-(2,4-Difluorophenyl)ethynyl]-3-nitro-pyridin-2-amine

Temperature

2.5 °C

6-Chloro-3-nitro-pyridin-2-ylamine (1254 g, 7.23 mol), triethylamine (1510 mL, 10.84 mol) and acetonitrile (10 L) are charged into a 20 L, 4-neck round bottom flask equipped with a mechanical stirrer under nitrogen. To the resulting yellow suspension, copper(I) iodide (13.9 g, 72.3 mmol) and bis(triphenylphosphine)palladium (II) chloride (50.72 g, 72.3 mmol) are added. The resulting pale orange suspension is cooled to 0-5° C. and then degassed during 10 min with nitrogen. A solution of 1-ethynyl-2,4-difluoro-benzene (1100 g, 7.95 mol) dissolved in acetonitrile (2.5 L) is added dropwise during 60 min. The resulting mixture is left stirring at RT (30° C.) overnight. The mixture is cooled to 0-5° C. Toluene (6 L) is added to the suspension and the mixture is stirred for 45 min and filtered though a frit. The solid is washed with toluene (3×3 L), water (2×3 L) and is dried overnight in a vacuum oven, to obtain the title compound as a yellow solid (1750 g, 92%). LC-ES/MS m/z 276 (M+1).

1. customequipped with a mechanical stirrer under nitrogen
2. customdegassed during 10 min with nitrogen
3. additionis added dropwise during 60 min
4. waitThe resulting mixture is left
5. temperatureThe mixture is cooled to 0-5° C
6. stirringthe mixture is stirred for 45 min
7. filtrationfiltered though a frit
8. washThe solid is washed with toluene (3×3 L), water (2×3 L)
9. customis dried overnight in a vacuum oven

ORD record

ord-b601a9bcae84437ab18343b2ab0f900a

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08288548B2