2-amino-N-(4-fluorophenyl)benzamide

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using the procedure described in Example 138, N-(4-fluorophenyl)-2-aminobenzamide (0.92 mmol) and N-(4-pyridyl)isonipecotoyl chloride (1.8 mmol), purifying with RPHPLC Method A, yielded 146 mg (35%) of the title compound. purifying with RPHPLC Method A

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of N-(4-fluorophenyl)-2-nitrobenzamide (4.0 g, 15.4 mmol) in methanol (220 mL) and tetrahydrofuran (110 mL) was added nickel acetate tetrahydrate (7.7 g, 31 mmol). Sodium borohydride (2.3 g, 62 mmol) was added in small portions. After gas evolution had ceased, the solvent was removed in vacuo. The residue was partitioned between ethyl acetate and concentrated ammonium hydroxide, and the layers were separated. The organic phase was washed with concentrated ammonium hydroxide and saturated aqueous sodium chloride solution, dried (magnesium sulfate), filtered, and concentrated in vacuo to give 2.86 g (81%) of the title compound as an off-white solid. the solvent was removed in vacuo The residue was partitioned between ethyl acetate and concentrated ammonium hydroxide the layers were separated The organic phase was washed with concentrated ammonium hydroxide and saturated aqueous sodium chloride solution dried (magnesium sulfate) filtered concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using the procedure described in Example 138, N-(4-fluorophenyl)-2-aminobenzamide (0.92 mmol) and N-(4-pyridyl)isonipecotoyl chloride (1.8 mmol), purifying with RPHPLC Method A, yielded 146 mg (35%) of the title compound. purifying with RPHPLC Method A

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using the procedure described in Example 138, N-(4-fluorophenyl)-2-aminobenzamide (0.92 mmol) and N-(4-pyridyl)isonipecotoyl chloride (1.8 mmol), purifying with RPHPLC Method A, yielded 146 mg (35%) of the title compound. purifying with RPHPLC Method A

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of N-(4-fluorophenyl)-2-nitrobenzamide (4.0 g, 15.4 mmol) in methanol (220 mL) and tetrahydrofuran (110 mL) was added nickel acetate tetrahydrate (7.7 g, 31 mmol). Sodium borohydride (2.3 g, 62 mmol) was added in small portions. After gas evolution had ceased, the solvent was removed in vacuo. The residue was partitioned between ethyl acetate and concentrated ammonium hydroxide, and the layers were separated. The organic phase was washed with concentrated ammonium hydroxide and saturated aqueous sodium chloride solution, dried (magnesium sulfate), filtered, and concentrated in vacuo to give 2.86 g (81%) of the title compound as an off-white solid. the solvent was removed in vacuo The residue was partitioned between ethyl acetate and concentrated ammonium hydroxide the layers were separated The organic phase was washed with concentrated ammonium hydroxide and saturated aqueous sodium chloride solution dried (magnesium sulfate) filtered concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using the procedure described in Example 138, N-(4-fluorophenyl)-2-aminobenzamide (0.92 mmol) and N-(4-pyridyl)isonipecotoyl chloride (1.8 mmol), purifying with RPHPLC Method A, yielded 146 mg (35%) of the title compound. purifying with RPHPLC Method A

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using the procedure described in Example 138, N-(4-fluorophenyl)-2-aminobenzamide (0.92 mmol) and N-(4-pyridyl)isonipecotoyl chloride (1.8 mmol), purifying with RPHPLC Method A, yielded 146 mg (35%) of the title compound. purifying with RPHPLC Method A

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of N-(4-fluorophenyl)-2-nitrobenzamide (4.0 g, 15.4 mmol) in methanol (220 mL) and tetrahydrofuran (110 mL) was added nickel acetate tetrahydrate (7.7 g, 31 mmol). Sodium borohydride (2.3 g, 62 mmol) was added in small portions. After gas evolution had ceased, the solvent was removed in vacuo. The residue was partitioned between ethyl acetate and concentrated ammonium hydroxide, and the layers were separated. The organic phase was washed with concentrated ammonium hydroxide and saturated aqueous sodium chloride solution, dried (magnesium sulfate), filtered, and concentrated in vacuo to give 2.86 g (81%) of the title compound as an off-white solid. the solvent was removed in vacuo The residue was partitioned between ethyl acetate and concentrated ammonium hydroxide the layers were separated The organic phase was washed with concentrated ammonium hydroxide and saturated aqueous sodium chloride solution dried (magnesium sulfate) filtered concentrated in vacuo

Conditions: temp:155.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-(2-hydroxy-ethoxy)-3,5-dimethyl-benzaldehyde (0.420 g, 2.17 mmol) and 2-amino-N-(4-fluoro-phenyl)-benzamide (0.500 g, 2.17 mmol) in N,N-dimethylacetamide (5 mL) was added sodium hydrogen sulfite (0.350 g, 3.26 mmol) and p-toluenesulfonic acid (0.21 g, 0.11 mmol). The reaction mixture was heated at 155° C. for 14 hours. The reaction mixture was cooled to room temperature and diluted with cold water (20 mL) to produce the precipitate. The yellow solid was filtered, washed with cold water (2×20 mL), methanol, and dried under vacuum to provide crude product, which was purified by column chromatography (silica gel 230-400 mesh; 10% EtOAc/hexane as eluent) to give the title compound as white solid. Yield: 0.10 g (11%). MP 95-97° C. 1H-NMR (400 MHz, CDCl3): δ 8.35 (d, 1H), 7.81-7.78 (d, 2H), 7.58-7.40 (m, 1H), 7.20-7.15 (m, 2H), 7.15-7.01 (m, 4H), 3.98-3.80 (m, 4H), 2.21 (s, 6H), 2.01 (t, 1H). MS (ES+) m/z: 405.01 (M+1). The reaction mixture was cooled to room temperature to produce the precipitate The yellow solid was filtered washed with cold water (2×20 mL), methanol dried under vacuum to provide crude product, which was purified by column chromatography (silica gel 230-400 mesh; 10% EtOAc/hexane as eluent)

Conditions: temp:115.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-fluoroaniline (2.40 mL, 24.5 mmol) in N,N-dimethylformamide (30 mL) was added isatoic anhydride (4.00 g, 24.5 mmol), and the reaction mixture was heated at 115° C. for 14 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (100 mL). The organic layer was washed with 1 N NaOH (200 mL), water (100 mL), then brine, and dried over Na2SO4. The solvent was removed under reduced pressure to give crude product, which was purified by column chromatography (silica gel 230-400 mesh; 10% EtOAc/hexane as eluent) to give 2-amino-N-(4-fluoro-phenyl)-benzamide as white solid. Yield: 2.00 g (35%). The reaction mixture was cooled to room temperature The organic layer was washed with 1 N NaOH (200 mL), water (100 mL) brine, and dried over Na2SO4 The solvent was removed under reduced pressure to give crude product, which was purified by column chromatography (silica gel 230-400 mesh; 10% EtOAc/hexane as eluent)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Using the procedure described in Example 138, N-(4-fluorophenyl)-2-aminobenzamide (0.92 mmol) and N-(4-pyridyl)isonipecotoyl chloride (1.8 mmol), purifying with RPHPLC Method A, yielded 146 mg (35%) of the title compound. purifying with RPHPLC Method A

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of N-(4-fluorophenyl)-2-nitrobenzamide (4.0 g, 15.4 mmol) in methanol (220 mL) and tetrahydrofuran (110 mL) was added nickel acetate tetrahydrate (7.7 g, 31 mmol). Sodium borohydride (2.3 g, 62 mmol) was added in small portions. After gas evolution had ceased, the solvent was removed in vacuo. The residue was partitioned between ethyl acetate and concentrated ammonium hydroxide, and the layers were separated. The organic phase was washed with concentrated ammonium hydroxide and saturated aqueous sodium chloride solution, dried (magnesium sulfate), filtered, and concentrated in vacuo to give 2.86 g (81%) of the title compound as an off-white solid. the solvent was removed in vacuo The residue was partitioned between ethyl acetate and concentrated ammonium hydroxide the layers were separated The organic phase was washed with concentrated ammonium hydroxide and saturated aqueous sodium chloride solution dried (magnesium sulfate) filtered concentrated in vacuo