2-(4-fluorophenyl)-N-methylacetamide

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(4-fluorophenyl)-N-methylacetamide (89 mg, 0.53 mmol) in 2 mL of THF at −78° C. was added MeLi in Et2O (1.6 M, 0.34 mL, 0.55 mmol). The solution was stirred at −78° C. for 5 min and then 20% phosgene in toluene (1.9 M, 0.29 mL, 0.55 mmol) was introduced quickly. After 2 min, 4-(4-amino-2-fluorophenoxy)picolinamide (Compound B′ of Example 24, 100 mg, 0.40 mmol) was added, followed by the addition of DMF (2 mL) and DIEA (0.4 mL). The reaction mixture was stirred at room temperature for 1 h and quenched with H2O. The solution was then extracted with EtOAc and the organic layer was washed with brine, dried over MgSO4. After filtration and concentration, the residue was purified by silica gel chromatography to give the title compound (77 mg, 33%). MS(ESI+) m/z 441 (M+H)+. After 2 min The reaction mixture was stirred at room temperature for 1 h quenched with H2O The solution was then extracted with EtOAc the organic layer was washed with brine dried over MgSO4 After filtration and concentration the residue was purified by silica gel chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methylamine in THF (2.0 M, 5 mL, 10 mmol) was added 4-fluorophenylacetyl chloride (518 mg, 3.0 mmol) at −78° C. The reaction mixture was stirred from −78° C. to room temperature for 1 h. The solution was diluted with H2O and extracted with EtOAc. The organic layer was washed with brine and dried over MgSO4. Filtration, followed by concentration, provided the title compound (490 mg, 98%). MS(ESI+) m/z 168 (M+H)+. extracted with EtOAc The organic layer was washed with brine dried over MgSO4 Filtration followed by concentration

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methylamine in THF (2.0 M, 5 mL, 10 mmol) was added 4-fluorophenylacetyl chloride (518 mg, 3.0 mmol) at −78° C. The reaction mixture was stirred from −78° C. to room temperature for 1 h. The solution was diluted with H2O and extracted with EtOAc. The organic layer was washed with brine and dried over MgSO4. Filtration, followed by concentration, provided the title compound (490 mg, 98%). MS(ESI+) m/z 168 (M+H)+. extracted with EtOAc The organic layer was washed with brine dried over MgSO4 Filtration followed by concentration

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(4-fluorophenyl)-N-methylacetamide (89 mg, 0.53 mmol) in 2 mL of THF at −78° C. was added MeLi in Et2O (1.6 M, 0.34 mL, 0.55 mmol). The solution was stirred at −78° C. for 5 min and then 20% phosgene in toluene (1.9 M, 0.29 mL, 0.55 mmol) was introduced quickly. After 2 min, 4-(4-amino-2-fluorophenoxy)picolinamide (Compound B′ of Example 24, 100 mg, 0.40 mmol) was added, followed by the addition of DMF (2 mL) and DIEA (0.4 mL). The reaction mixture was stirred at room temperature for 1 h and quenched with H2O. The solution was then extracted with EtOAc and the organic layer was washed with brine, dried over MgSO4. After filtration and concentration, the residue was purified by silica gel chromatography to give the title compound (77 mg, 33%). MS(ESI+) m/z 441 (M+H)+. After 2 min The reaction mixture was stirred at room temperature for 1 h quenched with H2O The solution was then extracted with EtOAc the organic layer was washed with brine dried over MgSO4 After filtration and concentration the residue was purified by silica gel chromatography

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(4-fluorophenyl)-N-methylacetamide (89 mg, 0.53 mmol) in 2 mL of THF at −78° C. was added MeLi in Et2O (1.6 M, 0.34 mL, 0.55 mmol). The solution was stirred at −78° C. for 5 min and then 20% phosgene in toluene (1.9 M, 0.29 mL, 0.55 mmol) was introduced quickly. After 2 min, 4-(4-amino-2-fluorophenoxy)picolinamide (Compound B′ of Example 24, 100 mg, 0.40 mmol) was added, followed by the addition of DMF (2 mL) and DIEA (0.4 mL). The reaction mixture was stirred at room temperature for 1 h and quenched with H2O. The solution was then extracted with EtOAc and the organic layer was washed with brine, dried over MgSO4. After filtration and concentration, the residue was purified by silica gel chromatography to give the title compound (77 mg, 33%). MS(ESI+) m/z 441 (M+H)+. After 2 min The reaction mixture was stirred at room temperature for 1 h quenched with H2O The solution was then extracted with EtOAc the organic layer was washed with brine dried over MgSO4 After filtration and concentration the residue was purified by silica gel chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methylamine in THF (2.0 M, 5 mL, 10 mmol) was added 4-fluorophenylacetyl chloride (518 mg, 3.0 mmol) at −78° C. The reaction mixture was stirred from −78° C. to room temperature for 1 h. The solution was diluted with H2O and extracted with EtOAc. The organic layer was washed with brine and dried over MgSO4. Filtration, followed by concentration, provided the title compound (490 mg, 98%). MS(ESI+) m/z 168 (M+H)+. extracted with EtOAc The organic layer was washed with brine dried over MgSO4 Filtration followed by concentration

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methylamine in THF (2.0 M, 5 mL, 10 mmol) was added 4-fluorophenylacetyl chloride (518 mg, 3.0 mmol) at −78° C. The reaction mixture was stirred from −78° C. to room temperature for 1 h. The solution was diluted with H2O and extracted with EtOAc. The organic layer was washed with brine and dried over MgSO4. Filtration, followed by concentration, provided the title compound (490 mg, 98%). MS(ESI+) m/z 168 (M+H)+. extracted with EtOAc The organic layer was washed with brine dried over MgSO4 Filtration followed by concentration

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(4-fluorophenyl)-N-methylacetamide (89 mg, 0.53 mmol) in 2 mL of THF at −78° C. was added MeLi in Et2O (1.6 M, 0.34 mL, 0.55 mmol). The solution was stirred at −78° C. for 5 min and then 20% phosgene in toluene (1.9 M, 0.29 mL, 0.55 mmol) was introduced quickly. After 2 min, 4-(4-amino-2-fluorophenoxy)picolinamide (Compound B′ of Example 24, 100 mg, 0.40 mmol) was added, followed by the addition of DMF (2 mL) and DIEA (0.4 mL). The reaction mixture was stirred at room temperature for 1 h and quenched with H2O. The solution was then extracted with EtOAc and the organic layer was washed with brine, dried over MgSO4. After filtration and concentration, the residue was purified by silica gel chromatography to give the title compound (77 mg, 33%). MS (ESI+) m/z 441 (M+H)+. After 2 min The reaction mixture was stirred at room temperature for 1 h quenched with H2O The solution was then extracted with EtOAc the organic layer was washed with brine dried over MgSO4 After filtration and concentration the residue was purified by silica gel chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of methylamine in THF (2.0 M, 5 mL, 10 mmol) was added 4-fluorophenylacetyl chloride (518 mg, 3.0 mmol) at −78° C. The reaction mixture was stirred from −78° C. to room temperature for 1 h. The solution was diluted with H2O and extracted with EtOAc. The organic layer was washed with brine and dried over MgSO4. Filtration, followed by concentration, provided the title compound (490 mg, 98%). MS (ESI+) m/z 168 (M+H)+. extracted with EtOAc The organic layer was washed with brine dried over MgSO4 Filtration followed by concentration