2-[(4-methylpiperazin-1-yl)methyl]aniline

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

Procedure: In 30 volume parts of ethanol is dissolved 1.87 parts of N1 -methyl-N4 -(2-nitrobenzyl)piperazine, followed by the addition of 3.0 parts of Raney nickel. Then, 3.0 parts of hydrazine hydrate is further added to the mixture and the entire mixture is kept at room temperature for 2 hours. Following this reaction, the Raney nickel is filtered off and the solvent is distilled off under reduced pressure. The residual oily substance is recrystallized from aqueous methanol. The procedure gives pale yellow crystals melting at 78° to 79° C. this reaction the Raney nickel is filtered off the solvent is distilled off under reduced pressure The residual oily substance is recrystallized from aqueous methanol

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

Procedure: In 30 volume parts of ethanol is dissolved 1.87 parts of N1 -methyl-N4 -(2-nitrobenzyl)piperazine, followed by the addition of 3.0 parts of Raney nickel. Then, 3.0 parts of hydrazine hydrate is further added to the mixture and the entire mixture is kept at room temperature for 2 hours. Following this reaction, the Raney nickel is filtered off and the solvent is distilled off under reduced pressure. The residual oily substance is recrystallized from aqueous methanol. The procedure gives pale yellow crystals melting at 78° to 79° C. this reaction the Raney nickel is filtered off the solvent is distilled off under reduced pressure The residual oily substance is recrystallized from aqueous methanol

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

Procedure: 5′-(3-Furoylamino)-2′-methyl-1,1′-biphenyl-4-carboxylic acid (50 mg, 0.156 mmol), 2-(4-methylpiperazin-1-ylmethyl)aniline (32.0 mg, 0.156 mmol), HATU (59.2 mg, 0.156 mmol), HOBT (21 mg, 0.156 mmol) and DIPEA (27 μl, 0.156 mmol) in DMF (2 ml) were stirred at room temperature for 18 h. The reaction was diluted with ethyl acetate (150 ml), washed with water (2×30 ml) and dried (magnesium sulphate). The solvent was evaporated under vacuum and the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2). Concentration of the product fractions under vacuum N-(6-methyl-4′-{[2-(4-methylpiperazin-1-ylmethyl)anilino]carbonyl}-1,1′-biphenyl-3-yl)-3-furamide (63 mg, 79%). NMR; δH [2H6]-DMSO includes 11.56,(1H, s), 9.94,(1H, s), 8.36-8.34,(2H, m), 8.02,(2H, d), 7-78,(1H, t), 7.68,(1H, dd), 7.64,(1H, d), 7.54,(2H, d), 7.35-7.25,(3H, m), 7.06,(1H, m), 6.98,(1H, m), 3.73,(2H, s), 2.22,(3H, s), 2.11, (3H, s). LCMS: retention time 2.60 min, MH+509. washed with water (2×30 ml) dried (magnesium sulphate) The solvent was evaporated under vacuum the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2)

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

Procedure: 5′-(3-Furoylamino)-2′-methyl-1,1′-biphenyl-4-carboxylic acid (50 mg, 0.156 mmol), 2-(4-methylpiperazin-1-ylmethyl)aniline (32.0 mg, 0.156 mmol), HATU (59.2 mg, 0.156 mmol), HOBT (21 mg, 0.156 mmol) and DIPEA (27 μl, 0.156 mmol) in DMF (2 ml) were stirred at room temperature for 18 h. The reaction was diluted with ethyl acetate (150 ml), washed with water (2×30 ml) and dried (magnesium sulphate). The solvent was evaporated under vacuum and the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2). Concentration of the product fractions under vacuum N-(6-methyl-4′-{[2-(4-methylpiperazin-1-ylmethyl)anilino]carbonyl}-1,1′-biphenyl-3-yl)-3-furamide (63 mg, 79%). NMR; δH [2H6]-DMSO includes 11.56,(1H, s), 9.94,(1H, s), 8.36–8.34,(2H, m), 8.02,(2H, d), 7.78,(1H, t), 7.68,(1H, d), 7.54,(2H, d), 7.35–7.25,(3H, m), 7.06,(1H, m), 6.98,(1H, m), 3.73,(2H, s), 2.22,(3H, s), 2.11,(3H, s). LCMS: retention time 2.60 min, MH+509. washed with water (2×30 ml) dried (magnesium sulphate) The solvent was evaporated under vacuum the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2)

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

Procedure: 5′-(3-Furoylamino)-2′-methyl-1,1′-biphenyl-4-carboxylic acid (50 mg, 0.156 mmol), 2-(4-methylpiperazin-1-ylmethyl)aniline (32.0 mg, 0.156 mmol), HATU (59.2 mg, 0.156 mmol), HOBT (21 mg, 0.156 mmol) and DIPEA (27 μl, 0.156 mmol) in DMF (2 ml) were stirred at room temperature for 18 h. The reaction was diluted with ethyl acetate (150 ml), washed with water (2×30 ml) and dried (magnesium sulphate). The solvent was evaporated under vacuum and the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2). Concentration of the product fractions under vacuum N-(6-methyl-4′-{[2-(4-methylpiperazin-1-ylmethyl)anilino]carbonyl}-1,1′-biphenyl-3-yl)-3-furamide (63 mg, 79%). NMR; δH [2H6]-DMSO includes 11.56,(1H, s), 9.94,(1H, s), 8.36–8.34,(2H, m), 8.02,(2H, d), 7.78,(1H, t), 7.68,(1H, d), 7.54,(2H, d), 7.35–7.25,(3H, m), 7.06,(1H, m), 6.98,(1H, m), 3.73,(2H, s), 2.22,(3H, s), 2.11,(3H, s). LCMS: retention time 2.60 min, MH+509. washed with water (2×30 ml) dried (magnesium sulphate) The solvent was evaporated under vacuum the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2)

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

Procedure: In 30 volume parts of ethanol is dissolved 1.87 parts of N1 -methyl-N4 -(2-nitrobenzyl)piperazine, followed by the addition of 3.0 parts of Raney nickel. Then, 3.0 parts of hydrazine hydrate is further added to the mixture and the entire mixture is kept at room temperature for 2 hours. Following this reaction, the Raney nickel is filtered off and the solvent is distilled off under reduced pressure. The residual oily substance is recrystallized from aqueous methanol. The procedure gives pale yellow crystals melting at 78° to 79° C. this reaction the Raney nickel is filtered off the solvent is distilled off under reduced pressure The residual oily substance is recrystallized from aqueous methanol

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

Procedure: 5′-(3-Furoylamino)-2′-methyl-1,1′-biphenyl-4-carboxylic acid (50 mg, 0.156 mmol), 2-(4-methylpiperazin-1-ylmethyl)aniline (32.0 mg, 0.156 mmol), HATU (59.2 mg, 0.156 mmol), HOBT (21 mg, 0.156 mmol) and DIPEA (27 μl, 0.156 mmol) in DMF (2 ml) were stirred at room temperature for 18 h. The reaction was diluted with ethyl acetate (150 ml), washed with water (2×30 ml) and dried (magnesium sulphate). The solvent was evaporated under vacuum and the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2). Concentration of the product fractions under vacuum N-(6-methyl-4′-{[2-(4-methylpiperazin-1-ylmethyl)anilino]carbonyl}-1,1′-biphenyl-3-yl)-3-furamide (63 mg, 79%). NMR; δH [2H6]-DMSO includes 11.56,(1H, s), 9.94,(1H, s), 8.36-8.34,(2H, m), 8.02,(2H, d), 7-78,(1H, t), 7.68,(1H, dd), 7.64,(1H, d), 7.54,(2H, d), 7.35-7.25,(3H, m), 7.06,(1H, m), 6.98,(1H, m), 3.73,(2H, s), 2.22,(3H, s), 2.11, (3H, s). LCMS: retention time 2.60 min, MH+509. washed with water (2×30 ml) dried (magnesium sulphate) The solvent was evaporated under vacuum the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2)

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

Procedure: 5′-(3-Furoylamino)-2′-methyl-1,1′-biphenyl-4-carboxylic acid (50 mg, 0.156 mmol), 2-(4-methylpiperazin-1-ylmethyl)aniline (32.0 mg, 0.156 mmol), HATU (59.2 mg, 0.156 mmol), HOBT (21 mg, 0.156 mmol) and DIPEA (27 μl, 0.156 mmol) in DMF (2 ml) were stirred at room temperature for 18 h. The reaction was diluted with ethyl acetate (150 ml), washed with water (2×30 ml) and dried (magnesium sulphate). The solvent was evaporated under vacuum and the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2). Concentration of the product fractions under vacuum N-(6-methyl-4′-{[2-(4-methylpiperazin-1-ylmethyl)anilino]carbonyl}-1,1′-biphenyl-3-yl)-3-furamide (63 mg, 79%). NMR; δH [2H6]-DMSO includes 11.56,(1H, s), 9.94,(1H, s), 8.36–8.34,(2H, m), 8.02,(2H, d), 7.78,(1H, t), 7.68,(1H, d), 7.54,(2H, d), 7.35–7.25,(3H, m), 7.06,(1H, m), 6.98,(1H, m), 3.73,(2H, s), 2.22,(3H, s), 2.11,(3H, s). LCMS: retention time 2.60 min, MH+509. washed with water (2×30 ml) dried (magnesium sulphate) The solvent was evaporated under vacuum the residue chromatographed on a silica flash column eluting with DCM/methanol/triethylamine (96:2:2)

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

Procedure: In 30 volume parts of ethanol is dissolved 1.87 parts of N1 -methyl-N4 -(2-nitrobenzyl)piperazine, followed by the addition of 3.0 parts of Raney nickel. Then, 3.0 parts of hydrazine hydrate is further added to the mixture and the entire mixture is kept at room temperature for 2 hours. Following this reaction, the Raney nickel is filtered off and the solvent is distilled off under reduced pressure. The residual oily substance is recrystallized from aqueous methanol. The procedure gives pale yellow crystals melting at 78° to 79° C. this reaction the Raney nickel is filtered off the solvent is distilled off under reduced pressure The residual oily substance is recrystallized from aqueous methanol