4-Chloro-N-methylpicolinamide → 4-(4-Amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide

Temperature

0 °C

A solution of 4-amino-3-fluorophenol (500 mg, 3.9 mmol) in N,N-dimethylacetamide (6 mL) cooled to 0° C. was treated with potassium tert-butoxide (441 mg, 3.9 mmol), and the brown solution was allowed to stir at 0° C. for 25 min. To the mixture was added 4-chloro-N-methyl-2-pyridinecarboxamide (516 mg, 3.0 mmol) as a solution in dimethylacetamide (4 mL). The reaction was heated at 100° C. for 16 h. The mixture was cooled to room temperature, quenched with H2O (20 mL), and extracted with ehtylacetate (4×40 mL). The combined organics were washed with H2O (2×30 mL), dried (MgSO4), and evaporated to afford a red-brown oil. 1H-NMR indicated the presence of residual dimethylacetamide, thus the oil was taken up in diethylether (50 mL) and was further washed with brine (5×30 mL). The organic layer was dried (MgSO4) and concentrated to give 950 mg of the desired product as a red-brown solid, which was used in the next step without purification.

1. temperatureThe reaction was heated at 100° C. for 16 h
2. temperatureThe mixture was cooled to room temperature
3. customquenched with H2O (20 mL)
4. extractionextracted with ehtylacetate (4×40 mL)
5. washThe combined organics were washed with H2O (2×30 mL)
6. dry with materialdried (MgSO4)
7. customevaporated
8. customto afford a red-brown oil
9. washwas further washed with brine (5×30 mL)
10. dry with materialThe organic layer was dried (MgSO4)
11. concentrationconcentrated

ORD record

ord-e64a254b84ed42f988c8b7779c790eb9

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08637553B2