2,4-Difluoroaniline → 5-Bromo-N-(2,4-difluorophenyl)-2-fluoronicotinamide

Temperature

40 °C

To a solution of 5-bromo-2-fluoronicotinic acid (55 mg, 0.25 mmol) in a mixture of 2.0 mL of THF and 5.0 mL of DCM was added (COCl)2 (0.13 mL, 1.5 mmol). The mixture was stirred at room temperature for 1 h and at 40° C. overnight. After cooling, the solvent was removed under reduced pressure. The residue was dissolved in 2.0 mL of DCM and to it were added 2,4-difluoroaniline (0.05 mL, 0.5 mmol) and 0.1 mL of TEA. The mixture was stirred at room temperature for 2 h and diluted with H2O. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine and dried over MgSO4. After filtration and concentration in vacuo, the residue was purified on preparative (RP) HPLC to give the desired product (60 mg, 73% yield). MS(ESI+) m/z 331.18, 333.18 (M+H)+.

1. temperatureAfter cooling
2. customthe solvent was removed under reduced pressure
3. dissolutionThe residue was dissolved in 2.0 mL of DCM and to it
4. stirringThe mixture was stirred at room temperature for 2 h
5. customThe organic layer was separated
6. extractionthe aqueous layer was extracted with EtOAc
7. washThe combined organic layers were washed with brine
8. dry with materialdried over MgSO4
9. filtrationAfter filtration and concentration in vacuo
10. customthe residue was purified on preparative (RP) HPLC

ORD record

ord-7c1a82c56ab7401e826aa28fb4a2624a

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07547782B2