N-(4-fluorophenyl)piperazine-1-carboxamide

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

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

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

Procedure: 1-tert-Butoxycarbonyl-4-(4-fluorophenylcarbamoyl)-piperazine (0.30 g) was dissolved in a solution of hydrogen chloride in ethyl acetate (4N, 2 ml), and the solution was stirred at ambient temperature for 1 hour. The solvent was removed by evaporation under reduced pressure to give 1-(4-fluorophenylcarbamoyl)piperazine as a white powder, which was taken up into dichloromethane (3 ml), and to the mixture were added in turn pyridine (0.25 ml), 4-trifluoromethoxybenzoyl chloride (0.146 ml), and catalytic amount of N,N-dimethylaminopyridine. After stirring at ambient temperature for 12 hours, the mixture was washed in turn with hydrochloric acid (0.5N), aqueous sodium hydrogen carbonate, and brine, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was chromatographed on silica gel (50 ml) eluting with 0%-3% methanol in dichloromethane to give 1-(4-fluorophenylcarbamoyl)-4-(4-trifluoromethoxybenzoyl)-piperazine (0.19 g). The solvent was removed by evaporation under reduced pressure

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

Procedure: The title compound was prepared from piperazine-1-carboxylic acid (4-fluoro-phenyl)-amide and piperonal. 1H NMR (400 MHz, CDCl3): 7.29-7.24 (m, 2H), 6.98-6.92 (m, 2H), 6.85 (s, 1H), 6.77-6.71 (m, 2H), 6.56 (s, 1H), 5.95 (s, 2H), 3.50-3.45 (m, 6H), 2.45 (t, J=5.1 Hz, 4H).

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

Procedure: The title compound was prepared from piperazine-1-carboxylic acid (4-fluoro-phenyl)-amide and 2-quinolinecarbaldehyde. 1H NMR (400 MHz, CDCl3): 8.16 (d, J=8.3 Hz, 1H), 8.08 (d, J=8.6 Hz, 1H), 7.82 (d, J=7.6 Hz, 1H), 7.74-6.69 (m, 1H), 7.63 (d, J=8.3 Hz, 1H), 7.56-7.52 (m, 1H), 7.32-7.25 (m, 2H), 6.99-6.94 (m, 2H), 6.38 (s, 1H), 3.88 (s, 2H), 3.52 (t, J=5.1 Hz, 4H), 2.60 (t, J=5.1 Hz, 4H).

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

Procedure: The title compound was prepared from piperazine-1-carboxylic acid (4-fluoro-phenyl)-amide and 2-naphthalenecarbaldehyde. 1H NMR (400 MHz, CDCl3): 7.85-7.80 (m, 3H), 7.74 (s, 1H), 7.52-7.45 (m, 3H), 7.30-7.25 (m, 2H), 6.98-6.92 (m, 2H), 6.36 (s, 1H), 3.69 (s, 2H), 3.49 (t, J=5.1 Hz, 4H), 2.51 (t, J=5.1 Hz, 4H).

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

Procedure: 1-tert-Butoxycarbonyl-4-(4-fluorophenylcarbamoyl)-piperazine (0.30 g) was dissolved in a solution of hydrogen chloride in ethyl acetate (4N, 2 ml), and the solution was stirred at ambient temperature for 1 hour. The solvent was removed by evaporation under reduced pressure to give 1-(4-fluorophenylcarbamoyl)piperazine as a white powder, which was taken up into dichloromethane (3 ml), and to the mixture were added in turn pyridine (0.25 ml), 4-trifluoromethoxybenzoyl chloride (0.146 ml), and catalytic amount of N,N-dimethylaminopyridine. After stirring at ambient temperature for 12 hours, the mixture was washed in turn with hydrochloric acid (0.5N), aqueous sodium hydrogen carbonate, and brine, dried over magnesium sulfate, and evaporated under reduced pressure. The residue was chromatographed on silica gel (50 ml) eluting with 0%-3% methanol in dichloromethane to give 1-(4-fluorophenylcarbamoyl)-4-(4-trifluoromethoxybenzoyl)-piperazine (0.19 g). The solvent was removed by evaporation under reduced pressure

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

Procedure: The title compound was prepared from piperazine-1-carboxylic acid (4-fluoro-phenyl)-amide and piperonal. 1H NMR (400 MHz, CDCl3): 7.29-7.24 (m, 2H), 6.98-6.92 (m, 2H), 6.85 (s, 1H), 6.77-6.71 (m, 2H), 6.56 (s, 1H), 5.95 (s, 2H), 3.50-3.45 (m, 6H), 2.45 (t, J=5.1 Hz, 4H).

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

Procedure: The title compound was prepared from piperazine-1-carboxylic acid (4-fluoro-phenyl)-amide and 2-quinolinecarbaldehyde. 1H NMR (400 MHz, CDCl3): 8.16 (d, J=8.3 Hz, 1H), 8.08 (d, J=8.6 Hz, 1H), 7.82 (d, J=7.6 Hz, 1H), 7.74-6.69 (m, 1H), 7.63 (d, J=8.3 Hz, 1H), 7.56-7.52 (m, 1H), 7.32-7.25 (m, 2H), 6.99-6.94 (m, 2H), 6.38 (s, 1H), 3.88 (s, 2H), 3.52 (t, J=5.1 Hz, 4H), 2.60 (t, J=5.1 Hz, 4H).

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

Procedure: The title compound was prepared from piperazine-1-carboxylic acid (4-fluoro-phenyl)-amide and 2-naphthalenecarbaldehyde. 1H NMR (400 MHz, CDCl3): 7.85-7.80 (m, 3H), 7.74 (s, 1H), 7.52-7.45 (m, 3H), 7.30-7.25 (m, 2H), 6.98-6.92 (m, 2H), 6.36 (s, 1H), 3.69 (s, 2H), 3.49 (t, J=5.1 Hz, 4H), 2.51 (t, J=5.1 Hz, 4H).

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

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