2-(2-fluorophenyl)propan-2-amine

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

Procedure: 3-Bromo-6-(5-bromo-2-fluorophenyl)-1,2,4-triazine (2.8 g, 8.4 mmol), 2-(2-fluorophenyl)propan-2-amine (2.0 g, 12.6 mmol), K2CO3 (2.3 g, 16.8 mmol) and CH3CN (20 mL) was heated to 90° C. The reaction mixture was diluted with EtOAc and washed with satd. aq. NaHCO3 and brine. The organic layer was dried over sodium sulfate, filtered, concentrated, and purified using silica gel chromatography to afford a yellow solid (2.3 g), m/z=406.1 [M+H]. washed with satd The organic layer was dried over sodium sulfate filtered concentrated purified

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

Procedure: IPEA (0.5 mL), EDC (192 mg) and HOBT (135 mg) were added to a solution of 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate (150 mg) and 1-(2-fluorophenyl)-1-methylethylamine (102 mg) in DMF (5 mL), and the reaction solution was stirred at room temperature for 3 hours. Water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The resulting organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) to obtain 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (1-(2-fluorophenyl)-1-methylethyl)amide. Sodium hydride (containing mineral oil at 40%, 40 mg) was added to a solution of the resulting 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (1-(2-fluorophenyl)-1-methylethyl)amide in DMF (5 mL), and the reaction solution was stirred at room temperature for 20 minutes. Water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The resulting organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) to obtain 70 mg of the title compound. The physical properties of the compound are as follows. the organic layer was partitioned The resulting organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system)

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

Procedure: t-Butyl alcohol (30 mL), diphenylphosphoryl azide (1.63 mL) and triethylamine (1.05 mL) were added to a solution of 2-(2-fluorophenyl)-2-methylpropionic acid (1.15 g) in toluene (60 mL), and the reaction solution was heated to reflux overnight. The reaction solution was returned to room temperature, and water and ethyl acetate were added thereto and the organic layer was partitioned. The resulting organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. 10 mL of 5 N hydrochloric acid was added to a solution of the residue in THF (5 mL), and the reaction solution was heated to reflux for 3 hours. The reaction solution was returned to room temperature, made basic with 5 N sodium hydroxide, and then extracted with ethyl acetate. The resulting organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain 735 mg of the title compound. The physical properties of the compound are as follows. the reaction solution was heated to reflux overnight was returned to room temperature the organic layer was partitioned The resulting organic layer was dried over magnesium sulfate the solvent was evaporated under reduced pressure 10 mL of 5 N hydrochloric acid was added to a solution of the residue in THF (5 mL) the reaction solution was heated to reflux for 3 hours was returned to room temperature extracted with ethyl acetate The resulting organic layer was dried over magnesium sulfate the solvent was evaporated under reduced pressure

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

Procedure: t-Butyl alcohol (30 mL), diphenylphosphoryl azide (1.63 mL) and triethylamine (1.05 mL) were added to a solution of 2-(2-fluorophenyl)-2-methylpropionic acid (1.15 g) in toluene (60 mL), and the reaction solution was heated to reflux overnight. The reaction solution was returned to room temperature, and water and ethyl acetate were added thereto and the organic layer was partitioned. The resulting organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. 10 mL of 5 N hydrochloric acid was added to a solution of the residue in THF (5 mL), and the reaction solution was heated to reflux for 3 hours. The reaction solution was returned to room temperature, made basic with 5 N sodium hydroxide, and then extracted with ethyl acetate. The resulting organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain 735 mg of the title compound. The physical properties of the compound are as follows. the reaction solution was heated to reflux overnight was returned to room temperature the organic layer was partitioned The resulting organic layer was dried over magnesium sulfate the solvent was evaporated under reduced pressure 10 mL of 5 N hydrochloric acid was added to a solution of the residue in THF (5 mL) the reaction solution was heated to reflux for 3 hours was returned to room temperature extracted with ethyl acetate The resulting organic layer was dried over magnesium sulfate the solvent was evaporated under reduced pressure

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

Procedure: IPEA (0.5 mL), EDC (192 mg) and HOBT (135 mg) were added to a solution of 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate (150 mg) and 1-(2-fluorophenyl)-1-methylethylamine (102 mg) in DMF (5 mL), and the reaction solution was stirred at room temperature for 3 hours. Water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The resulting organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent:heptane-ethyl acetate system→ethyl acetate-methanol system) to obtain 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (1-(2-fluorophenyl)-1-methylethyl)amide. Sodium hydride (containing mineral oil at 40%, 40 mg) was added to a solution of the resulting 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (1-(2-fluorophenyl)-1-methylethyl)amide in DMF (5 mL), and the reaction solution was stirred at room temperature for 20 minutes. Water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The resulting organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent:heptane-ethyl acetate system→ethyl acetate-methanol system) to obtain 70 mg of the title compound. The physical properties of the compound are as follows. the organic layer was partitioned The resulting organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent:heptane-ethyl acetate system→ethyl acetate-methanol system)

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

Procedure: t-Butyl alcohol (30 mL), diphenylphosphoryl azide (1.63 mL) and triethylamine (1.05 mL) were added to a solution of 2-(2-fluorophenyl)-2-methylpropionic acid (1.15 g) in toluene (60 mL), and the reaction solution was heated to reflux overnight. The reaction solution was returned to room temperature, and water and ethyl acetate were added thereto and the organic layer was partitioned. The resulting organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. 10 mL of 5 N hydrochloric acid was added to a solution of the residue in THF (5 mL), and the reaction solution was heated to reflux for 3 hours. The reaction solution was returned to room temperature, made basic with 5 N sodium hydroxide, and then extracted with ethyl acetate. The resulting organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain 735 mg of the title compound. The physical properties of the compound are as follows. the reaction solution was heated to reflux overnight was returned to room temperature the organic layer was partitioned The resulting organic layer was dried over magnesium sulfate the solvent was evaporated under reduced pressure 10 mL of 5 N hydrochloric acid was added to a solution of the residue in THF (5 mL) the reaction solution was heated to reflux for 3 hours was returned to room temperature extracted with ethyl acetate The resulting organic layer was dried over magnesium sulfate the solvent was evaporated under reduced pressure

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

Procedure: IPEA (0.5 mL), EDC (192 mg) and HOBT (135 mg) were added to a solution of 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid trifluoroacetate (150 mg) and 1-(2-fluorophenyl)-1-methylethylamine (102 mg) in DMF (5 mL), and the reaction solution was stirred at room temperature for 3 hours. Water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The resulting organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) to obtain 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (1-(2-fluorophenyl)-1-methylethyl)amide. Sodium hydride (containing mineral oil at 40%, 40 mg) was added to a solution of the resulting 5-chloro-2-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene)valeric acid (1-(2-fluorophenyl)-1-methylethyl)amide in DMF (5 mL), and the reaction solution was stirred at room temperature for 20 minutes. Water and ethyl acetate were added to the reaction solution and the organic layer was partitioned. The resulting organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) to obtain 70 mg of the title compound. The physical properties of the compound are as follows. the organic layer was partitioned The resulting organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (Carrier: Chromatorex™ NH, elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system)

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

Procedure: t-Butyl alcohol (30 mL), diphenylphosphoryl azide (1.63 mL) and triethylamine (1.05 mL) were added to a solution of 2-(2-fluorophenyl)-2-methylpropionic acid (1.15 g) in toluene (60 mL), and the reaction solution was heated to reflux overnight. The reaction solution was returned to room temperature, and water and ethyl acetate were added thereto and the organic layer was partitioned. The resulting organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. 10 mL of 5 N hydrochloric acid was added to a solution of the residue in THF (5 mL), and the reaction solution was heated to reflux for 3 hours. The reaction solution was returned to room temperature, made basic with 5 N sodium hydroxide, and then extracted with ethyl acetate. The resulting organic layer was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to obtain 735 mg of the title compound. The physical properties of the compound are as follows. the reaction solution was heated to reflux overnight was returned to room temperature the organic layer was partitioned The resulting organic layer was dried over magnesium sulfate the solvent was evaporated under reduced pressure 10 mL of 5 N hydrochloric acid was added to a solution of the residue in THF (5 mL) the reaction solution was heated to reflux for 3 hours was returned to room temperature extracted with ethyl acetate The resulting organic layer was dried over magnesium sulfate the solvent was evaporated under reduced pressure