2-chloro-N-(3-fluorophenyl)acetamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 283 mg of 1-[bis(4-fluorophenyl)methyl]-3,3-dimethylpiperazine and 204 mg of N-(3-fluorophenyl)chloroacetamide was dissolved in 20 ml of a 1:1 by volume mixture of tetrahydrofuran and N,N-dimethylformamide, and 1 g of anhydrous potassium carbonate was added to the resulting solution. The reaction mixture was then stirred at 80° C. for 16 hours, after which ethyl acetate was added, and the organic layer was separated. The organic layer was washed with water and dried over anhydrous magnesium sulfate. The solvent was then removed by evaporation under reduced pressure. The residue was subjected to silica gel thin layer chromatography using a 2:1 by volume mixture of cyclohexane and ethyl acetate as the developing solvent, to give a purified 1-[bis(4-fluorophenyl)methyl]-4-[(3-fluorophenyl)carbamoylmethyl]-3,3-dimethylpiperazine. was added to the resulting solution the organic layer was separated The organic layer was washed with water dried over anhydrous magnesium sulfate The solvent was then removed by evaporation under reduced pressure by volume mixture of cyclohexane and ethyl acetate as the developing solvent

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 300 mg of 1-[bis(4-fluorophenyl)methyl]piperazine and 234 mg of N-(3-fluorophenyl)chloroacetamide was dissolved in 20 ml of a 1:1 by volume mixture of tetrahydrofuran and N,N-dimethylformamide, and 400 mg of anhydrous potassium carbonate were added to the solution. The reaction mixture was then stirred at 70° C. for 2 hours, after which ethyl acetate was added to it and the organic layer was separated. The organic layer was washed three times with water, and then dried over anhydrous magnesium sulfate. The solvent was removed by evaporation under reduced pressure. The residue was subjected to silica gel thin layer chromatography using a 2:1 by volume mixture of cyclohexane and ethyl acetate as the developing solvent, to give a purified 1-[bis(4-fluorophenyl)methyl]-4-(3-fluorophenylcarbamoylmethyl)piperazine. were added to the solution the organic layer was separated The organic layer was washed three times with water dried over anhydrous magnesium sulfate The solvent was removed by evaporation under reduced pressure by volume mixture of cyclohexane and ethyl acetate as the developing solvent

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-(4-nitro-1H-pyrazol-3-yl)acetamide (0.380 g, 2.25 mmol), 2-chloro-N-(3-fluorophenyl)acetamide (0.420 g, 2.25 mmol) and potassium carbonate (00.370 g, 2.7 mmol) in dimethyl formamide (10 ml) was heated at 50° C. for 1 hour. The mixture was filtered and the filtrate was evaporated. The residue was triturated with a mixture of 2% methanol in dichloromethane and then with diethyl ether to give 2-[3-(acetylamino)-4-nitro-1H-pyrazol-1-yl]-N-(3-fluorophenyl)acetamide The mixture was filtered the filtrate was evaporated The residue was triturated with a mixture of 2% methanol in dichloromethane

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-(4-nitro-1H-pyrazol-3-yl)acetamide (0.380 g, 2.25 mmol), 2-chloro-N-(3-fluorophenyl)acetamide (0.420 g, 2.25 mmol) and potassium carbonate (00.370 g, 2.7 mmol) in dimethyl formamide (10 ml) was heated at 50° C. for 1 hour. The mixture was filtered and the filtrate was evaporated. The residue was triturated with a mixture of 2% methanol in dichloromethane and then with diethyl ether to give 2-[3-(acetylamino)-4-nitro-1H-pyrazol-1-yl]-N-(3-fluorophenyl)acetamide The mixture was filtered the filtrate was evaporated The residue was triturated with a mixture of 2% methanol in dichloromethane

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

Procedure: A mixture of ethyl 4-nitro-1H-pyrazole-3-carboxylate (0.685 g, 3.7 mmol) and 2-chloro-N-(3-fluorophenyl) acetamide (0.694 g, 3.7 mmol) and potassium carbonate (0.613 g, 4.44 mmol) in dimethyl formamide (10 ml) was stirred at room temperature for 20 hours. The mixture was evaporated and the residue was purified by silica gel chromatography eluting with a 8 to 10% mixture of ethyl acetate in dichloromethane to give ethyl 1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-4-nitro-1H-pyrazole-3-carboxylate (0.920 g, 74% yield): The mixture was evaporated the residue was purified by silica gel chromatography eluting with a 8 to 10% mixture of ethyl acetate in dichloromethane

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

Procedure: A mixture of ethyl 4-nitro-1H-pyrazole-3-carboxylate (0.685 g, 3.7 mmol) and 2-chloro-N-(3-fluorophenyl) acetamide (0.694 g, 3.7 mmol) and potassium carbonate (0.613 g, 4.44 mmol) in dimethyl formamide (10 ml) was stirred at room temperature for 20 hours. The mixture was evaporated and the residue was purified by silica gel chromatography eluting with a 8 to 10% mixture of ethyl acetate in dichloromethane to give ethyl 1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-4-nitro-1H-pyrazole-3-carboxylate (0.920 g, 74% yield): The mixture was evaporated the residue was purified by silica gel chromatography eluting with a 8 to 10% mixture of ethyl acetate in dichloromethane

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

Procedure: A mixture of 2-chloro-N-(3-fluorophenyl)acetamide (0.65 g, 3.46 mmol), 4-nitro-1H-pyrazole-3-carboxamide (0.54 g, 3.46 mmol) and potassium carbonate (0.57 g, 4.13 mmol) in dimethylformamide (10 ml) was stirred at room temperature for 48 hours. The mixture was evaporated and the residue partitioned between ethyl acetate and water. The organic phase was separated, washed, dried and then concentrated to yield 1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-4-nitro-1H-pyrazole-3-carboxamide (730 mg, 69% yield). The mixture was evaporated the residue partitioned between ethyl acetate and water The organic phase was separated washed dried concentrated

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

Procedure: A mixture of 2-chloro-N-(3-fluorophenyl)acetamide (0.65 g, 3.46 mmol), 4-nitro-1H-pyrazole-3-carboxamide (0.54 g, 3.46 mmol) and potassium carbonate (0.57 g, 4.13 mmol) in dimethylformamide (10 ml) was stirred at room temperature for 48 hours. The mixture was evaporated and the residue partitioned between ethyl acetate and water. The organic phase was separated, washed, dried and then concentrated to yield 1-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-4-nitro-1H-pyrazole-3-carboxamide (730 mg, 69% yield). The mixture was evaporated the residue partitioned between ethyl acetate and water The organic phase was separated washed dried concentrated

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir: