2-piperazin-1-ylbenzamide

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

Procedure: 1-(2-Carbamoylphenyl)piperazine (300 mg, 1.5 mmol) was dissolved in water (2 ml) and 1,4-dioxane (2 ml) The resulting solution was mixed with sodium bicarbonate (250 mg, 2.9 mmol) and di-t-butyl carbonate (480 mg, 2.2 mmol), and then stirred at a room temperature for 4 hours. The reaction solution was mixed with water (20 ml), and the reaction product was extracted with chloroform (80 ml) and washed with water and saturated brine. Then the solvent was evaporated under a reduced pressure to obtain colorless crystals. Thereafter, the crystals were washed with hexane and then dried to obtain 430 mg of the title compound (1.4 mmol, 96% in yield). the reaction product was extracted with chloroform (80 ml) washed with water and saturated brine Then the solvent was evaporated under a reduced pressure to obtain colorless crystals Thereafter, the crystals were washed with hexane dried

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

Procedure: 1-(2-Carbamoylphenyl)piperazine (300 mg, 1.5 mmol) was dissolved in water (2 ml) and 1,4-dioxane (2 ml) The resulting solution was mixed with sodium bicarbonate (250 mg, 2.9 mmol) and di-t-butyl carbonate (480 mg, 2.2 mmol), and then stirred at a room temperature for 4 hours. The reaction solution was mixed with water (20 ml), and the reaction product was extracted with chloroform (80 ml) and washed with water and saturated brine. Then the solvent was evaporated under a reduced pressure to obtain colorless crystals. Thereafter, the crystals were washed with hexane and then dried to obtain 430 mg of the title compound (1.4 mmol, 96% in yield). the reaction product was extracted with chloroform (80 ml) washed with water and saturated brine Then the solvent was evaporated under a reduced pressure to obtain colorless crystals Thereafter, the crystals were washed with hexane dried

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

Procedure: 1-(2-Cyanophenyl)piperazine (1.8 g, 9.8 mmol) was dissolved in 90% sulfuric acid aqueous solution (20 ml) and stirred at a room temperature for 24 hours. The reaction solution was slowly added dropwise to a mixture of ice (75 g) and 28% aqueous ammonia (75 ml), and the reaction product was extracted with chloroform. The extract was washed with saturated brine and dried with sodium sulfate. Then the compound obtained by the evaporation of the solvent under a reduced pressure was separated by an aluminum column chromatography to obtain colorless crystals. By further recrystallizing the thus obtained crystals from ethyl acetate, 680 mg of the title compound was obtained (3.1 mmol, 32% in yield). the reaction product was extracted with chloroform The extract was washed with saturated brine dried with sodium sulfate Then the compound obtained by the evaporation of the solvent under a reduced pressure was separated by an aluminum column chromatography to obtain colorless crystals By further recrystallizing the thus obtained crystals from ethyl acetate

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

Procedure: 1-(2-Cyanophenyl)piperazine (1.8 g, 9.8 mmol) was dissolved in 90% sulfuric acid aqueous solution (20 ml) and stirred at a room temperature for 24 hours. The reaction solution was slowly added dropwise to a mixture of ice (75 g) and 28% aqueous ammonia (75 ml), and the reaction product was extracted with chloroform. The extract was washed with saturated brine and dried with sodium sulfate. Then the compound obtained by the evaporation of the solvent under a reduced pressure was separated by an aluminum column chromatography to obtain colorless crystals. By further recrystallizing the thus obtained crystals from ethyl acetate, 680 mg of the title compound was obtained (3.1 mmol, 32% in yield). the reaction product was extracted with chloroform The extract was washed with saturated brine dried with sodium sulfate Then the compound obtained by the evaporation of the solvent under a reduced pressure was separated by an aluminum column chromatography to obtain colorless crystals By further recrystallizing the thus obtained crystals from ethyl acetate

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

Procedure: 1-(2-Carbamoylphenyl)piperazine (300 mg, 1.5 mmol) was dissolved in water (2 ml) and 1,4-dioxane (2 ml) The resulting solution was mixed with sodium bicarbonate (250 mg, 2.9 mmol) and di-t-butyl carbonate (480 mg, 2.2 mmol), and then stirred at a room temperature for 4 hours. The reaction solution was mixed with water (20 ml), and the reaction product was extracted with chloroform (80 ml) and washed with water and saturated brine. Then the solvent was evaporated under a reduced pressure to obtain colorless crystals. Thereafter, the crystals were washed with hexane and then dried to obtain 430 mg of the title compound (1.4 mmol, 96% in yield). the reaction product was extracted with chloroform (80 ml) washed with water and saturated brine Then the solvent was evaporated under a reduced pressure to obtain colorless crystals Thereafter, the crystals were washed with hexane dried

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

Procedure: 1-(2-Cyanophenyl)piperazine (1.8 g, 9.8 mmol) was dissolved in 90% sulfuric acid aqueous solution (20 ml) and stirred at a room temperature for 24 hours. The reaction solution was slowly added dropwise to a mixture of ice (75 g) and 28% aqueous ammonia (75 ml), and the reaction product was extracted with chloroform. The extract was washed with saturated brine and dried with sodium sulfate. Then the compound obtained by the evaporation of the solvent under a reduced pressure was separated by an aluminum column chromatography to obtain colorless crystals. By further recrystallizing the thus obtained crystals from ethyl acetate, 680 mg of the title compound was obtained (3.1 mmol, 32% in yield). the reaction product was extracted with chloroform The extract was washed with saturated brine dried with sodium sulfate Then the compound obtained by the evaporation of the solvent under a reduced pressure was separated by an aluminum column chromatography to obtain colorless crystals By further recrystallizing the thus obtained crystals from ethyl acetate

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

Procedure: Following the general procedure of Example 11 and making non-critical variations, 6-chloro-2-(chloromethyl)imidazo[1,2-α]pyridine (Example 4, Step 1; 0.306 g) and 2-(piperazin-1-yl)benzamide (0.336 g) are converted to 0.236 g of the title compound after chromatography on silica gel using methanol/dichloromethane (8/92) and crystallization from ethyl acetate/dichloromethane. A portion of this material was recrystallized from ethyl acetate/methanol/hexane; mp 178-179° C.; ms m/z 369; IR (mineral oil) 1663, 3289, 1325, 1448, 796 cm-1 ; 1H NMR (CDCl3) δ2.75, 3.08, 3.78, 5.76, 7.13, 7.23, 7.46, 7.52, 7.53, 8.14, 8.17, 9.57.

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

Procedure: 1-(2-Carbamoylphenyl)piperazine (300 mg, 1.5 mmol) was dissolved in water (2 ml) and 1,4-dioxane (2 ml) The resulting solution was mixed with sodium bicarbonate (250 mg, 2.9 mmol) and di-t-butyl carbonate (480 mg, 2.2 mmol), and then stirred at a room temperature for 4 hours. The reaction solution was mixed with water (20 ml), and the reaction product was extracted with chloroform (80 ml) and washed with water and saturated brine. Then the solvent was evaporated under a reduced pressure to obtain colorless crystals. Thereafter, the crystals were washed with hexane and then dried to obtain 430 mg of the title compound (1.4 mmol, 96% in yield). the reaction product was extracted with chloroform (80 ml) washed with water and saturated brine Then the solvent was evaporated under a reduced pressure to obtain colorless crystals Thereafter, the crystals were washed with hexane dried

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

Procedure: 1-(2-Cyanophenyl)piperazine (1.8 g, 9.8 mmol) was dissolved in 90% sulfuric acid aqueous solution (20 ml) and stirred at a room temperature for 24 hours. The reaction solution was slowly added dropwise to a mixture of ice (75 g) and 28% aqueous ammonia (75 ml), and the reaction product was extracted with chloroform. The extract was washed with saturated brine and dried with sodium sulfate. Then the compound obtained by the evaporation of the solvent under a reduced pressure was separated by an aluminum column chromatography to obtain colorless crystals. By further recrystallizing the thus obtained crystals from ethyl acetate, 680 mg of the title compound was obtained (3.1 mmol, 32% in yield). the reaction product was extracted with chloroform The extract was washed with saturated brine dried with sodium sulfate Then the compound obtained by the evaporation of the solvent under a reduced pressure was separated by an aluminum column chromatography to obtain colorless crystals By further recrystallizing the thus obtained crystals from ethyl acetate