1-methylpiperazine;dihydrochloride

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

実験手順: LiA1H4 (7.6 g, 200 mmol) was suspended under stirring at 0° under Ar in anhydrous THF (400 ml), then N-methylpiperazine dihydrochloride (17.3 g, 100 mmol) was added portionwise in 10 min. N-methylpiperazine (30 g, 300 mmol) was then added dropwise, the mixture was warmed to RT and stirring continued for 2 hours. The surnatant of this suspension was then added by syringe to a stirred solution at 0° under Ar of benzothiophen-2-carboxylic acid (7.13 g, 40.0 mmol) in anhydrous THF (200 ml). The mixture was refluxed for 4 hours and after the same procedure as in preparation 6 pure title compound was obtained (4.6 g, 28.4 mmol, yield 70.9%) as dark orange crystals. The mixture was refluxed for 4 hours

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

実験手順: LiA1H4 (3.04 g, 80 mmol) was suspended under stirring at 0° under Ar in anhydrous THF (150 ml), then N-methylpiperazine dihydrochloride (6.92 g, 40 mmol) was added portionwise in 10 minutes. N-methylpiperazine (12 g, 120 mmol) was then added dropwise, the mixture was warmed to RT and stirring continued for 2 hours. The surnatant of this suspension was then added by syringe to a stirred solution at 0° under Ar of 5-chlorobenzofuran-2-carboxylic acid (2.95 g, 15.0 mmol) in anhydrous THF (50 ml). The mixture was refluxed for 4 hours and after cooling to RT the suspension was diluted with Et2O (400 ml). The resulting mixture was poured into water (500 ml) and the organic phase was decanted. The aqueous phase was extracted with Et2O (2×300 ml) and the pooled organic extracts were washed with 2N NaOH (200 ml), 1N HCl (200 ml) and brine (200 ml). After drying (MgSO4) and concentration a brown oily residue was obtained. This was chromatographed on silicagel (n-heptane/EtOAc 3/1). The pooled fractions produced after evaporation pure title compound (850 mg, 4.71 mmol, yield 31.4%) as brown needles. The mixture was refluxed for 4 hours after cooling to RT the suspension the organic phase was decanted The aqueous phase was extracted with Et2O (2×300 ml) the pooled organic extracts were washed with 2N NaOH (200 ml), 1N HCl (200 ml) and brine (200 ml) After drying (MgSO4) and concentration a brown oily residue was obtained This was chromatographed on silicagel (n-heptane/EtOAc 3/1) The pooled fractions produced

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

実験手順: To a solution of 23.6 grams of 2-phenyl-3-acetylbenzofuran in 100 milliliters of isopropanol were added 4.2 grams of paraformaldehyde and 19.1 grams of N-methylpiperazine dihydrochloride and the mixture was heated under gentle reflux for a period of 12 hours. The dihydrochloride of the compound named in the heading of this example precipitated from the reaction mixture and was separated therefrom by suction filtration, washed with a small quantity of ethanol, and recrystallized from ethanol. The dihydrochloride had a melting point of 174°-177°C and 22.8 grams thereof was thus obtained. the mixture was heated under gentle reflux for a period of 12 hours precipitated from the reaction mixture was separated by suction filtration washed with a small quantity of ethanol recrystallized from ethanol thereof was thus obtained

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

実験手順: LiA1H4 (7.6 g, 200 mmol) was suspended under stirring at 0° under Ar in anhydrous THF (400 ml), then N-methylpiperazine dihydrochloride (17.3 g, 100 mmol) was added portionwise in 10 min. N-methylpiperazine (30 g, 300 mmol) was then added dropwise, the mixture was warmed to RT and stirring continued for 2 hours. The surnatant of this suspension was then added by syringe to a stirred solution at 0° under Ar of benzothiophen-2-carboxylic acid (7.13 g, 40.0 mmol) in anhydrous THF (200 ml). The mixture was refluxed for 4 hours and after the same procedure as in preparation 6 pure title compound was obtained (4.6 g, 28.4 mmol, yield 70.9%) as dark orange crystals. The mixture was refluxed for 4 hours

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

実験手順: LiA1H4 (3.04 g, 80 mmol) was suspended under stirring at 0° under Ar in anhydrous THF (150 ml), then N-methylpiperazine dihydrochloride (6.92 g, 40 mmol) was added portionwise in 10 minutes. N-methylpiperazine (12 g, 120 mmol) was then added dropwise, the mixture was warmed to RT and stirring continued for 2 hours. The surnatant of this suspension was then added by syringe to a stirred solution at 0° under Ar of 5-chlorobenzofuran-2-carboxylic acid (2.95 g, 15.0 mmol) in anhydrous THF (50 ml). The mixture was refluxed for 4 hours and after cooling to RT the suspension was diluted with Et2O (400 ml). The resulting mixture was poured into water (500 ml) and the organic phase was decanted. The aqueous phase was extracted with Et2O (2×300 ml) and the pooled organic extracts were washed with 2N NaOH (200 ml), 1N HCl (200 ml) and brine (200 ml). After drying (MgSO4) and concentration a brown oily residue was obtained. This was chromatographed on silicagel (n-heptane/EtOAc 3/1). The pooled fractions produced after evaporation pure title compound (850 mg, 4.71 mmol, yield 31.4%) as brown needles. The mixture was refluxed for 4 hours after cooling to RT the suspension the organic phase was decanted The aqueous phase was extracted with Et2O (2×300 ml) the pooled organic extracts were washed with 2N NaOH (200 ml), 1N HCl (200 ml) and brine (200 ml) After drying (MgSO4) and concentration a brown oily residue was obtained This was chromatographed on silicagel (n-heptane/EtOAc 3/1) The pooled fractions produced

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

実験手順: LiA1H4 (3.04 g, 80 mmol) was suspended under stirring at 0° under Ar in anhydrous THF (150 ml), then N-methylpiperazine dihydrochloride (6.92 g, 40 mmol) was added portionwise in 10 minutes. N-methylpiperazine (12 g, 120 mmol) was then added dropwise, the mixture was warmed to RT and stirring continued for 2 hours. The surnatant of this suspension was then added by syringe to a stirred solution at 0° under Ar of 5-chlorobenzofuran-2-carboxylic acid (2.95 g, 15.0 mmol) in anhydrous THF (50 ml). The mixture was refluxed for 4 hours and after cooling to RT the suspension was diluted with Et2O (400 ml). The resulting mixture was poured into water (500 ml) and the organic phase was decanted. The aqueous phase was extracted with Et2O (2×300 ml) and the pooled organic extracts were washed with 2N NaOH (200 ml), 1N HCl (200 ml) and brine (200 ml). After drying (MgSO4) and concentration a brown oily residue was obtained. This was chromatographed on silicagel (n-heptane/EtOAc 3/1). The pooled fractions produced after evaporation pure title compound (850 mg, 4.71 mmol, yield 31.4%) as brown needles. The mixture was refluxed for 4 hours after cooling to RT the suspension the organic phase was decanted The aqueous phase was extracted with Et2O (2×300 ml) the pooled organic extracts were washed with 2N NaOH (200 ml), 1N HCl (200 ml) and brine (200 ml) After drying (MgSO4) and concentration a brown oily residue was obtained This was chromatographed on silicagel (n-heptane/EtOAc 3/1) The pooled fractions produced

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

実験手順: To a suspension of 1-methylpiperazine dihydrochloride (8.5 g, 49.2 mmol) and triethylamine (22.8 mL, 164.0 mmol) in THF (150 mL) was added tert-butyl 2-bromoacetate (8.0 g, 41.0 mmol). The mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted with EtOAc (200 mL) and H2O (100 mL). The organic phase was washed with brine, dried (MgSO4), filtered and concentrated to dryness. The residue was purified by column chromatography (silica, 0-10% MeOH in CH2Cl2) to afford the sub-title compound (6.0 g, 69%). The organic phase was washed with brine dried (MgSO4) filtered concentrated to dryness The residue was purified by column chromatography (silica, 0-10% MeOH in CH2Cl2)

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

実験手順: To a solution of 3-bromofuran-2-carbaldehyde (500 mg, 2.85 mmol), 1-methylpiperazine dihydrochloride (986 mg, 5.71 mmol) and triethylamine (1.5 mL, 11.4 mmol) in CH2Cl2 (10 mL) was added sodium triacetoxyborohydride (1.2 g, 5.71 mmol). The mixture was stirred at room temperature for 12 hours. The reaction mixture was diluted with EtOAc (100 mL). The organic phase was washed with aqueous NaHCO3 and brine then dried (MgSO4), filtered and concentrated to dryness. The residue was purified by column chromatography (silica, 0-10% MeOH in CH2Cl2) to afford the sub-title compound (570 mg, 78%). The organic phase was washed with aqueous NaHCO3 and brine then dried (MgSO4) filtered concentrated to dryness The residue was purified by column chromatography (silica, 0-10% MeOH in CH2Cl2)

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

実験手順: To a solution of 23.6 grams of 2-phenyl-3-acetylbenzofuran in 100 milliliters of isopropanol were added 4.2 grams of paraformaldehyde and 19.1 grams of N-methylpiperazine dihydrochloride and the mixture was heated under gentle reflux for a period of 12 hours. The dihydrochloride of the compound named in the heading of this example precipitated from the reaction mixture and was separated therefrom by suction filtration, washed with a small quantity of ethanol, and recrystallized from ethanol. The dihydrochloride had a melting point of 174°-177°C and 22.8 grams thereof was thus obtained. the mixture was heated under gentle reflux for a period of 12 hours precipitated from the reaction mixture was separated by suction filtration washed with a small quantity of ethanol recrystallized from ethanol thereof was thus obtained

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

実験手順: LiA1H4 (7.6 g, 200 mmol) was suspended under stirring at 0° under Ar in anhydrous THF (400 ml), then N-methylpiperazine dihydrochloride (17.3 g, 100 mmol) was added portionwise in 10 min. N-methylpiperazine (30 g, 300 mmol) was then added dropwise, the mixture was warmed to RT and stirring continued for 2 hours. The surnatant of this suspension was then added by syringe to a stirred solution at 0° under Ar of benzothiophen-2-carboxylic acid (7.13 g, 40.0 mmol) in anhydrous THF (200 ml). The mixture was refluxed for 4 hours and after the same procedure as in preparation 6 pure title compound was obtained (4.6 g, 28.4 mmol, yield 70.9%) as dark orange crystals. The mixture was refluxed for 4 hours

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

実験手順: LiA1H4 (3.04 g, 80 mmol) was suspended under stirring at 0° under Ar in anhydrous THF (150 ml), then N-methylpiperazine dihydrochloride (6.92 g, 40 mmol) was added portionwise in 10 minutes. N-methylpiperazine (12 g, 120 mmol) was then added dropwise, the mixture was warmed to RT and stirring continued for 2 hours. The surnatant of this suspension was then added by syringe to a stirred solution at 0° under Ar of 5-chlorobenzofuran-2-carboxylic acid (2.95 g, 15.0 mmol) in anhydrous THF (50 ml). The mixture was refluxed for 4 hours and after cooling to RT the suspension was diluted with Et2O (400 ml). The resulting mixture was poured into water (500 ml) and the organic phase was decanted. The aqueous phase was extracted with Et2O (2×300 ml) and the pooled organic extracts were washed with 2N NaOH (200 ml), 1N HCl (200 ml) and brine (200 ml). After drying (MgSO4) and concentration a brown oily residue was obtained. This was chromatographed on silicagel (n-heptane/EtOAc 3/1). The pooled fractions produced after evaporation pure title compound (850 mg, 4.71 mmol, yield 31.4%) as brown needles. The mixture was refluxed for 4 hours after cooling to RT the suspension the organic phase was decanted The aqueous phase was extracted with Et2O (2×300 ml) the pooled organic extracts were washed with 2N NaOH (200 ml), 1N HCl (200 ml) and brine (200 ml) After drying (MgSO4) and concentration a brown oily residue was obtained This was chromatographed on silicagel (n-heptane/EtOAc 3/1) The pooled fractions produced