N-phenyl-2-piperazin-1-ylacetamide

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 2-amino-4,5-dichloro-3-nitropyridine (0.031 g, 0.15 mmol) and isopropanol (3.5 ml) was added N-phenyl-2-piperazin-1-yl-acetamide×2HCl salt (0.048 g, 0.16 mmol) followed by diisopropylethylamine (0.10 ml, 0.54 mmol). The reaction mixture was heated at 45° C. for 18 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column which was eluted with 10% to 30% ethyl acetate in dichloromethane. The title compound was obtained as a yellow solid (0.041 g, 71%); 1H-NMR (500 MHz, DMSO-d6) 2.64 (br s, 4H, piperazine N(CH2)2), 3.13 (br s, 4H, piperazine N(CH2)2), 3.19 (s, 2H, NCH2CO), 7.00 (br s, 2H, 2-NH2), 7.06 (t, J=7.34 Hz, 1H, p-ArH), 7.31 (t, J=8.26 Hz, 2H, m-ArH), 7.63 (d, J=7.34 Hz, 2H, o-ArH), 8.07 (s, 1H, 6-H), 9.76 (s, 1H, CONH); to cool to room temperature the solvents were removed in vacuo The residue was absorbed on silica gel was eluted with 10% to 30% ethyl acetate in dichloromethane

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 5-bromo-4-chloro-3-nitro-pyridin-2-ylamine (0.126 g, 0.50 mmol) and isopropanol (10 ml) was added N-phenyl-2-piperazin-1-yl-acetamide×2HCl salt (0.160 g, 0.55 mmol) followed by diisopropylethylamine (0.32 ml, 1.76 mmol). The reaction mixture was heated at 45° C. for 18 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column which was eluted with 30% ethyl acetate in dichloromethane. The title compound was obtained as a pale yellow solid (0.134 g, 62%); 1H-NMR (500 MHz, DMSO-d6) 2.67 (br s, 4H, piperazine N(CH2)2), 3.12 (br s, 4H, piperazine N(CH2)2), 3.19 (s, 2H, NCH2CO), 7.06 (m, 3H, 2-NH2, p-ArH), 7.31 (t, J=7.44 Hz, 2H, m-ArH), 7.62 (d, J=8.29 Hz, 2H, o-ArH), 8.16 (s, 1H, 6-H), 9.76 (s, 1H, CONH); to cool to room temperature the solvents were removed in vacuo The residue was absorbed on silica gel was eluted with 30% ethyl acetate in dichloromethane

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 2-amino-4,5-dichloro-3-nitropyridine (0.031 g, 0.15 mmol) and isopropanol (3.5 ml) was added N-phenyl-2-piperazin-1-yl-acetamide×2HCl salt (0.048 g, 0.16 mmol) followed by diisopropylethylamine (0.10 ml, 0.54 mmol). The reaction mixture was heated at 45° C. for 18 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column which was eluted with 10% to 30% ethyl acetate in dichloromethane. The title compound was obtained as a yellow solid (0.041 g, 71%); 1H-NMR (500 MHz, DMSO-d6) 2.64 (br s, 4H, piperazine N(CH2)2), 3.13 (br s, 4H, piperazine N(CH2)2), 3.19 (s, 2H, NCH2CO), 7.00 (br s, 2H, 2-NH2), 7.06 (t, J=7.34 Hz, 1H, p-ArH), 7.31 (t, J=8.26 Hz, 2H, m-ArH), 7.63 (d, J=7.34 Hz, 2H, o-ArH), 8.07 (s, 1H, 6-H), 9.76 (s, 1H, CONH); to cool to room temperature the solvents were removed in vacuo The residue was absorbed on silica gel was eluted with 10% to 30% ethyl acetate in dichloromethane

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 5-bromo-4-chloro-3-nitro-pyridin-2-ylamine (0.126 g, 0.50 mmol) and isopropanol (10 ml) was added N-phenyl-2-piperazin-1-yl-acetamide×2HCl salt (0.160 g, 0.55 mmol) followed by diisopropylethylamine (0.32 ml, 1.76 mmol). The reaction mixture was heated at 45° C. for 18 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column which was eluted with 30% ethyl acetate in dichloromethane. The title compound was obtained as a pale yellow solid (0.134 g, 62%); 1H-NMR (500 MHz, DMSO-d6) 2.67 (br s, 4H, piperazine N(CH2)2), 3.12 (br s, 4H, piperazine N(CH2)2), 3.19 (s, 2H, NCH2CO), 7.06 (m, 3H, 2-NH2, p-ArH), 7.31 (t, J=7.44 Hz, 2H, m-ArH), 7.62 (d, J=8.29 Hz, 2H, o-ArH), 8.16 (s, 1H, 6-H), 9.76 (s, 1H, CONH); to cool to room temperature the solvents were removed in vacuo The residue was absorbed on silica gel was eluted with 30% ethyl acetate in dichloromethane

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 5-bromo-4-chloro-3-nitro-pyridin-2-ylamine (0.126 g, 0.50 mmol) and isopropanol (10 ml) was added N-phenyl-2-piperazin-1-yl-acetamide×2HCl salt (0.160 g, 0.55 mmol) followed by diisopropylethylamine (0.32 ml, 1.76 mmol). The reaction mixture was heated at 45° C. for 18 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column which was eluted with 30% ethyl acetate in dichloromethane. The title compound was obtained as a pale yellow solid (0.134 g, 62%); 1H-NMR (500 MHz, DMSO-d6) 2.67 (br s, 4H, piperazine N(CH2)2), 3.12 (br s, 4H, piperazine N(CH2)2), 3.19 (s, 2H, NCH2CO), 7.06 (m, 3H, 2-NH2, p-ArH), 7.31 (t, J=7.44 Hz, 2H, m-ArH), 7.62 (d, J=8.29 Hz, 2H, o-ArH), 8.16 (s, 1H, 6-H), 9.76 (s, 1H, CONH); to cool to room temperature the solvents were removed in vacuo The residue was absorbed on silica gel was eluted with 30% ethyl acetate in dichloromethane

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 2-amino-4,5-dichloro-3-nitropyridine (0.031 g, 0.15 mmol) and isopropanol (3.5 ml) was added N-phenyl-2-piperazin-1-yl-acetamide×2HCl salt (0.048 g, 0.16 mmol) followed by diisopropylethylamine (0.10 ml, 0.54 mmol). The reaction mixture was heated at 45° C. for 18 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column which was eluted with 10% to 30% ethyl acetate in dichloromethane. The title compound was obtained as a yellow solid (0.041 g, 71%); 1H-NMR (500 MHz, DMSO-d6) 2.64 (br s, 4H, piperazine N(CH2)2), 3.13 (br s, 4H, piperazine N(CH2)2), 3.19 (s, 2H, NCH2CO), 7.00 (br s, 2H, 2-NH2), 7.06 (t, J=7.34 Hz, 1H, p-ArH), 7.31 (t, J=8.26 Hz, 2H, m-ArH), 7.63 (d, J=7.34 Hz, 2H, o-ArH), 8.07 (s, 1H, 6-H), 9.76 (s, 1H, CONH); to cool to room temperature the solvents were removed in vacuo The residue was absorbed on silica gel was eluted with 10% to 30% ethyl acetate in dichloromethane

Conditions: temp:45.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 5-bromo-4-chloro-3-nitro-pyridin-2-ylamine (0.126 g, 0.50 mmol) and isopropanol (10 ml) was added N-phenyl-2-piperazin-1-yl-acetamide×2HCl salt (0.160 g, 0.55 mmol) followed by diisopropylethylamine (0.32 ml, 1.76 mmol). The reaction mixture was heated at 45° C. for 18 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column which was eluted with 30% ethyl acetate in dichloromethane. The title compound was obtained as a pale yellow solid (0.134 g, 62%); 1H-NMR (500 MHz, DMSO-d6) 2.67 (br s, 4H, piperazine N(CH2)2), 3.12 (br s, 4H, piperazine N(CH2)2), 3.19 (s, 2H, NCH2CO), 7.06 (m, 3H, 2-NH2, p-ArH), 7.31 (t, J=7.44 Hz, 2H, m-ArH), 7.62 (d, J=8.29 Hz, 2H, o-ArH), 8.16 (s, 1H, 6-H), 9.76 (s, 1H, CONH); to cool to room temperature the solvents were removed in vacuo The residue was absorbed on silica gel was eluted with 30% ethyl acetate in dichloromethane