Hydrochloric Acid → 5-Bromo-3-[(2,2-difluoroethyl)amino]thiophene-2-carboxamide

Temperature

60 °C

To a solution of methyl 5-bromo-3-[(2,2-difluoroethyl)amino]thiophene-2-carboxylate (285 mg, 0.95 mmol) in MeOH (3.0 mL) was added a solution of sodium hydroxide (114 mg, 2.85 mmol) in water (1.5 mL). After stirring at 60° C. for 4 h, 6 M aqueous HCl (0.3 mL) was added to the mixture to adjust the pH to 10. After removal of the solvent at reduced pressure, the residue was diluted with DMF (5 mL). Then, triethylamine (2.6 mL, 19 mmol) and ammonium chloride (1.02 g, 19 mmol) were added. After stirring at room temperature for 5 min, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (1.09 g, 5.70 mmol) and 1-hydroxybenzotriazole (0.77 g, 5.70 mmol) were added to the mixture and the stirring was continued for 17 h. Then, water and EtOAc were added to quench the reaction. The organic materials were extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and filtered. After removal of the solvent at reduced pressure, the residue was purified by column chromatography (Purif, silica gel, hexane to 70:30 hexane/EtOAc) to give the title compound (130 mg, 48%) as a yellow solid:

1. customAfter removal of the solvent at reduced pressure
2. additionthe residue was diluted with DMF (5 mL)
3. stirringAfter stirring at room temperature for 5 min
4. waitthe stirring was continued for 17 h
5. customto quench
6. customthe reaction
7. extractionThe organic materials were extracted with EtOAc
8. washThe combined extracts were washed with water and brine
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. customAfter removal of the solvent at reduced pressure
12. customthe residue was purified by column chromatography (Purif, silica gel, hexane to 70:30 hexane/EtOAc)

ORD record

ord-d4110f7fc5034fafadfca71aaca77cde

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691828B2