1-(3-chloro-2-methylphenyl)piperazine

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 3-chloro-2-methylaniline (21.6 g, 0.15 mol) in n-butanol (200 ml) was added bis(2-chloroethyl)amine hydrochloride (30 g, 0.17 mol) at room temperature and allowed to refluxed temperature for 2 days. After cooled to room temperature Na2CO3 (9 g, 0.08 mol) was added and then reaction mixture was refluxed 30 min. The resulting mixture was filtered with n-butanol (100 ml) and collected solid was dried under reduced pressure to be obtained title compound (24.8 g, 81%) as white solid. to refluxed temperature for 2 days was added reaction mixture was refluxed 30 min The resulting mixture was filtered with n-butanol (100 ml) collected solid was dried under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 3-chloro-2-methylaniline (21.6 g, 0.15 mol) in n-butanol (200 ml) was added bis(2-chloroethyl)amine hydrochloride (30 g, 0.17 mol) at room temperature and allowed to refluxed temperature for 2 days. After cooled to room temperature Na2CO3 (9 g, 0.08 mol) was added and then reaction mixture was refluxed 30 min. The resulting mixture was filtered with n-butanol (100 ml) and collected solid was dried under reduced pressure to be obtained title compound (24.8 g, 81%) as white solid. to refluxed temperature for 2 days was added reaction mixture was refluxed 30 min The resulting mixture was filtered with n-butanol (100 ml) collected solid was dried under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 3-chloro-2-methylaniline (21.6 g, 0.15 mol) in n-butanol (200 ml) was added bis(2-chloroethyl)amine hydrochloride (30 g, 0.17 mol) at room temperature and allowed to refluxed temperature for 2 days. After cooled to room temperature Na2CO3 (9 g, 0.08 mol) was added and then reaction mixture was refluxed 30 min. The resulting mixture was filtered with n-butanol (100 ml) and collected solid was dried under reduced pressure to be obtained title compound (24.8 g, 81%) as white solid. to refluxed temperature for 2 days was added reaction mixture was refluxed 30 min The resulting mixture was filtered with n-butanol (100 ml) collected solid was dried under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5,6-dimethoxy-1-(3,4-dimethoxybenzyl)-1H-indazole-3-acetic acid (41.0 g) was suspended in dichloromethane (500 ml). Then 2,2-dipyridyl disulfide (24.5 g) and triphenylphosphine (30.0 g) were added thereto and the mixture was stirred at room temperature. Next, (3-chloro-2-methyl-phenyl)piperazine (23.5 g) dissolved in dichloromethane (200 ml) was dropped thereinto within 5 minutes and the mixture was stirred at room temperature for 30 minutes. Then dichloromethane (1000 ml) was added to the reaction mixture. After washing with water, the organic layer was dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue thus obtained was purified by using a silica gel column (ethyl acetate/hexane=2/1, silica gel 2 kg) to give 61.5 g of a colorless solid. This solid product was used in the subsequent reaction without purification. A small amount of this product was taken and recrystallized from ethanol. Thus colorless prism crystals (m.p.: 165°-169° C.) were obtained. was dropped the mixture was stirred at room temperature for 30 minutes After washing with water the organic layer was dried over sodium sulfate filtered evaporated under reduced pressure The residue thus obtained was purified

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5,6-dimethoxy-1-(3,4-dimethoxybenzyl)-1H-indazole-3-acetic acid (41.0 g) was suspended in dichloromethane (500 ml). Then 2,2-dipyridyl disulfide (24.5 g) and triphenylphosphine (30.0 g) were added thereto and the mixture was stirred at room temperature. Next, (3-chloro-2-methyl-phenyl)piperazine (23.5 g) dissolved in dichloromethane (200 ml) was dropped thereinto within 5 minutes and the mixture was stirred at room temperature for 30 minutes. Then dichloromethane (1000 ml) was added to the reaction mixture. After washing with water, the organic layer was dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue thus obtained was purified by using a silica gel column (ethyl acetate/hexane=2/1, silica gel 2 kg) to give 61.5 g of a colorless solid. This solid product was used in the subsequent reaction without purification. A small amount of this product was taken and recrystallized from ethanol. Thus colorless prism crystals (m.p.: 165°-169° C.) were obtained. was dropped the mixture was stirred at room temperature for 30 minutes After washing with water the organic layer was dried over sodium sulfate filtered evaporated under reduced pressure The residue thus obtained was purified

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 3-chloro-2-methylaniline (compound 26, 21.6 g, 0.15 mol) in n-butanol (200 ml) was added bis(2-chloroethyl)amine hydrochloride (compound 27, 30 g, 0.17 mol) at room temperature and allowed to refluxed temperature for 2 days. After cooled to room temperature Na2CO3 (9 g, 0.08 mol) was added and then reaction mixture was refluxed 30 min. The resulting mixture was filtered with n-butanol (100 ml) and collected solid was dried under reduced pressure to be obtained title compound (24.8 g, 81%) as a white solid. to refluxed temperature for 2 days was added reaction mixture was refluxed 30 min The resulting mixture was filtered with n-butanol (100 ml) collected solid was dried under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 3-chloro-2-methylaniline (21.6 g, 0.15 mol) in n-butanol (200 ml) was added bis(2-chloroethyl)amine hydrochloride (30 g, 0.17 mol) at room temperature and allowed to refluxed temperature for 2 days. After cooled to room temperature Na2CO3 (9 g, 0.08 mol) was added and then reaction mixture was refluxed 30 min. The resulting mixture was filtered with n-butanol (100 ml) and collected solid was dried under reduced pressure to be obtained title compound (24.8 g, 81%) as white solid. to refluxed temperature for 2 days was added reaction mixture was refluxed 30 min The resulting mixture was filtered with n-butanol (100 ml) collected solid was dried under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 3-chloro-2-methylaniline (21.6 g, 0.15 mol) in n-butanol (200 ml) was added bis(2-chloroethyl)amine hydrochloride (30 g, 0.17 mol) at room temperature and allowed to refluxed temperature for 2 days. After cooled to room temperature Na2CO3 (9 g, 0.08 mol) was added and then reaction mixture was refluxed 30 min. The resulting mixture was filtered with n-butanol (100 ml) and collected solid was dried under reduced pressure to be obtained title compound (24.8 g, 81%) as white solid. to refluxed temperature for 2 days was added reaction mixture was refluxed 30 min The resulting mixture was filtered with n-butanol (100 ml) collected solid was dried under reduced pressure