2-AMINO-N-(4-CHLORO-PHENYL)-BENZAMIDE

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

Procedure: Using the procedure described in Example 93, Part A, 2-amino-N-(4-chlorophenyl)benzamide (5 g, 20.3 mmol) and isonicotinoyl chloride hydrochloride (3.97 g, 22.3 mmol) yielded 6.48 g (91%) of the title compound.

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

Procedure: Using the procedure described in Example 138, N-(4-chlorophenyl)-2-aminobenzamide (0.97 mmol) and N-(4-pyridyl)isonipecotoyl chloride (1.8 mmol), purifying with RPHPLC Method A, yielded 334 mg (37%) of the title compound. purifying with RPHPLC Method A

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

Procedure: A mixture of benzoxazine-2,4-dione (1.6 g, 10 mmol) and 4-chloroaniline (2.5 g, 20 mmol) in 1,4-dioxane (30 mL) was heated at reflux for 15 hours. After cooling the solid was filtered, and the filtrate was concentrated, washed with ethyl ether. The washing was concentrated further to a solid. Additional washing with cold ethyl ether (10 mL) afforded N-(4-chlorophenyl)-2-aminobenzamide as a tan solid; NMR (DMSO-d6) 10.1 (s, 1), 7.8 (d, 2), 7.6 (d, 1), 7.4 (d, 2), 7.2 (t, 1), 6.8 (d, 1), 6.6 (t, 1), 6.3 (s, 2) ppm. was heated at reflux for 15 hours After cooling the solid was filtered the filtrate was concentrated washed with ethyl ether The washing was concentrated further to a solid Additional washing with cold ethyl ether (10 mL)

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

Procedure: A mixture of benzoxazine-2,4-dione (1.6 g, 10 mmol) and 4-chloroaniline (2.5 g, 20 mmol) in 1,4-dioxane (30 mL) was heated at reflux for 15 hours. After cooling the solid was filtered, and the filtrate was concentrated, washed with ethyl ether. The washing was concentrated further to a solid. Additional washing with cold ethyl ether (10 mL) afforded N-(4-chlorophenyl)-2-aminobenzamide as a tan solid; NMR (DMSO-d6) 10.1 (s, 1), 7.8 (d, 2), 7.6 (d, 1), 7.4 (d, 2), 7.2 (t, 1), 6.8 (d, 1), 6.6 (t, 1), 6.3 (s, 2) ppm. was heated at reflux for 15 hours After cooling the solid was filtered the filtrate was concentrated washed with ethyl ether The washing was concentrated further to a solid Additional washing with cold ethyl ether (10 mL)

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

Procedure: To a mixture of 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(N,N-dimethyl-amino)benzoic acid (950 mg, 2.61 mmol), pyridine (0.23 mL, 2.86 mmol), DMF (1 drop) and methylene chloride (15 mL) was added oxalyl chloride (0.24 mL, 2.73 mmol) dropwise. After 15 minutes, more pyridine (0.23 mL, 2.86 mmol) was added, followed by the N-(4-chlorophenyl)-2-aminobenzamide (645 mg, 2.61 mmol). The reaction was stirred for 1 hour, diluted with methylene chloride, washed with 50% saturated aqueous sodium bicarbonate, and dried over Na2 SO4. The organic solution was concentrated, chromatographed (2000 g silica, 5% EtOAc/CH2Cl2 to 15% EtOAc/CH2Cl2), and triturated with ether to give the desired product (1.32 g, 83%). washed with 50% saturated aqueous sodium bicarbonate dried over Na2 SO4 The organic solution was concentrated chromatographed (2000 g silica, 5% EtOAc/CH2Cl2 to 15% EtOAc/CH2Cl2) triturated with ether

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

Procedure: To a mixture of 2-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(N,N-dimethyl-amino)benzoic acid (950 mg, 2.61 mmol), pyridine (0.23 mL, 2.86 mmol), DMF (1 drop) and methylene chloride (15 mL) was added oxalyl chloride (0.24 mL, 2.73 mmol) dropwise. After 15 minutes, more pyridine (0.23 mL, 2.86 mmol) was added, followed by the N-(4-chlorophenyl)-2-aminobenzamide (645 mg, 2.61 mmol). The reaction was stirred for 1 hour, diluted with methylene chloride, washed with 50% saturated aqueous sodium bicarbonate, and dried over Na2 SO4. The organic solution was concentrated, chromatographed (2000 g silica, 5% EtOAc/CH2Cl2 to 15% EtOAc/CH2Cl2), and triturated with ether to give the desired product (1.32 g, 83%). washed with 50% saturated aqueous sodium bicarbonate dried over Na2 SO4 The organic solution was concentrated chromatographed (2000 g silica, 5% EtOAc/CH2Cl2 to 15% EtOAc/CH2Cl2) triturated with ether

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 20 g (123 mmol) isatoic anhydride (formed by treating anthranilic acid with phosgene) and 15.64 g (123 mmol) 4-chloroaniline was heated at 120° C. for 2 hours. The reaction was cooled to room temperature, mixed with CH2Cl2 and filtered. The reaction was cooled to room temperature filtered

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

Procedure: Using the procedure described in Example 93, Part A, 2-amino-N-(4-chlorophenyl)benzamide (5 g, 20.3 mmol) and isonicotinoyl chloride hydrochloride (3.97 g, 22.3 mmol) yielded 6.48 g (91%) of the title compound.

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

Procedure: Using the procedure described in Example 93, Part A, 2-amino-N-(4-chlorophenyl)benzamide (5 g, 20.3 mmol) and isonicotinoyl chloride hydrochloride (3.97 g, 22.3 mmol) yielded 6.48 g (91%) of the title compound.

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

Procedure: Using the procedure described in Example 138, N-(4-chlorophenyl)-2-aminobenzamide (0.97 mmol) and N-(4-pyridyl)isonipecotoyl chloride (1.8 mmol), purifying with RPHPLC Method A, yielded 334 mg (37%) 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-chlorophenyl)-2-aminobenzamide (0.97 mmol) and N-(4-pyridyl)isonipecotoyl chloride (1.8 mmol), purifying with RPHPLC Method A, yielded 334 mg (37%) 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 93, Part A, 2-amino-N-(4-chlorophenyl)benzamide (5 g, 20.3 mmol) and isonicotinoyl chloride hydrochloride (3.97 g, 22.3 mmol) yielded 6.48 g (91%) of the title compound.