N-[(1-benzylpiperidin-4-yl)methyl]ethanamine

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

Procedure: 1-Benzyl-4-[(N-ethylamino)methyl]piperidine (EXAMPLE 261, 5.68 g) and 2-chloro-3-nitropyridine (3.87 g) are dissolved in 96 ml of acetonitrile and 4.05 g of solid potassium bicarbonate is added. The reaction is refluxed for 20 hr, cooled to 20°-25°, poured into water and extracted with ethyl acetate. The organic extracts are dried (sodium sulfate), and concentrated under reduced pressure. Purification by flash column chromatography (15% ethyl acetate/hexane to 80% ethyl acetate/hexane) gives the title compound, HRMS calcd. for C20H26N4O2 =354.2056, found=354.2045. The reaction is refluxed for 20 hr cooled to 20°-25° extracted with ethyl acetate The organic extracts are dried (sodium sulfate) concentrated under reduced pressure Purification by flash column chromatography (15% ethyl acetate/hexane to 80% ethyl acetate/hexane)

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

Procedure: 1-Benzyl-4-[N-ethylamino]methylpiperidine (EXAMPLE 175, 7.59, 32.64 mmol), 2-chloro-3-nitropyridine (5.17 g, 32.64 mmol) and potassium carbonate (5.41 g, 39.17 mmol) in acetonitrile (0.25M) are refluxed 48 hr. The mixture is diluted with water and extracted with ethyl acetate and then dichloromethane. The combined extracts are dried over sodium sulfate, concentrated and chromatographed (silica gel column, 300 g; eluting with 15-80% ethyl acetate/hexane), to give the title compound, NMR (300 MHz, CD3OD) 8.43, 8.20, 7.42, 6.90, 3.61, 3.52, 3.49, 3.00, 2.10, 1.80, 1.37 and 1.25δ. extracted with ethyl acetate The combined extracts are dried over sodium sulfate concentrated chromatographed (silica gel column, 300 g; eluting with 15-80% ethyl acetate/hexane)

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

Procedure: N-Ethyl-1-benzyl-4-piperidinyl carboxamide (EXAMPLE 174, 8.03 g, 32.60 mmol) is dissolved in THF and cooled to 0°. Lithium aluminum hydride (1M in THF) is added dropwise. The solution is refluxed 4.5 hr, then quenched at 0° by adding 1.24 ml water, 1.24 ml 15% aqueous sodium hydride, and 3.71 ml water. Filtration through a pad of diatomaceous earth and sodium sulfate and then evaporation of the solvent gives the title compound; NMR (300 MHz, CDCl3) 7.14, 3.32, 2.73, 2.50, 2.35, 1.79, 1.55, 1.34, 1.12 and 0.97δ. cooled to 0° The solution is refluxed 4.5 hr quenched at 0° by adding 1.24 ml water, 1.24 ml 15% aqueous sodium hydride, and 3.71 ml water Filtration through a pad of diatomaceous earth and sodium sulfate evaporation of the solvent

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

Procedure: 1-Benzyl-4-[(N-ethylamino)methyl]piperidine (EXAMPLE 261, 5.68 g) and 2-chloro-3-nitropyridine (3.87 g) are dissolved in 96 ml of acetonitrile and 4.05 g of solid potassium bicarbonate is added. The reaction is refluxed for 20 hr, cooled to 20°-25°, poured into water and extracted with ethyl acetate. The organic extracts are dried (sodium sulfate), and concentrated under reduced pressure. Purification by flash column chromatography (15% ethyl acetate/hexane to 80% ethyl acetate/hexane) gives the title compound, HRMS calcd. for C20H26N4O2 =354.2056, found=354.2045. The reaction is refluxed for 20 hr cooled to 20°-25° extracted with ethyl acetate The organic extracts are dried (sodium sulfate) concentrated under reduced pressure Purification by flash column chromatography (15% ethyl acetate/hexane to 80% ethyl acetate/hexane)

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

Procedure: 1-Benzyl-4-[(N-ethylamino)methyl]piperidine (EXAMPLE 261, 5.68 g) and 2-chloro-3-nitropyridine (3.87 g) are dissolved in 96 ml of acetonitrile and 4.05 g of solid potassium bicarbonate is added. The reaction is refluxed for 20 hr, cooled to 20°-25°, poured into water and extracted with ethyl acetate. The organic extracts are dried (sodium sulfate), and concentrated under reduced pressure. Purification by flash column chromatography (15% ethyl acetate/hexane to 80% ethyl acetate/hexane) gives the title compound, HRMS calcd. for C20H26N4O2 =354.2056, found=354.2045. The reaction is refluxed for 20 hr cooled to 20°-25° extracted with ethyl acetate The organic extracts are dried (sodium sulfate) concentrated under reduced pressure Purification by flash column chromatography (15% ethyl acetate/hexane to 80% ethyl acetate/hexane)

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

Procedure: 1-Benzyl-4-[N-ethylamino]methylpiperidine (EXAMPLE 175, 7.59, 32.64 mmol), 2-chloro-3-nitropyridine (5.17 g, 32.64 mmol) and potassium carbonate (5.41 g, 39.17 mmol) in acetonitrile (0.25M) are refluxed 48 hr. The mixture is diluted with water and extracted with ethyl acetate and then dichloromethane. The combined extracts are dried over sodium sulfate, concentrated and chromatographed (silica gel column, 300 g; eluting with 15-80% ethyl acetate/hexane), to give the title compound, NMR (300 MHz, CD3OD) 8.43, 8.20, 7.42, 6.90, 3.61, 3.52, 3.49, 3.00, 2.10, 1.80, 1.37 and 1.25δ. extracted with ethyl acetate The combined extracts are dried over sodium sulfate concentrated chromatographed (silica gel column, 300 g; eluting with 15-80% ethyl acetate/hexane)

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

Procedure: N-Ethyl-1-benzyl-4-piperidinyl carboxamide (EXAMPLE 174, 8.03 g, 32.60 mmol) is dissolved in THF and cooled to 0°. Lithium aluminum hydride (1M in THF) is added dropwise. The solution is refluxed 4.5 hr, then quenched at 0° by adding 1.24 ml water, 1.24 ml 15% aqueous sodium hydride, and 3.71 ml water. Filtration through a pad of diatomaceous earth and sodium sulfate and then evaporation of the solvent gives the title compound; NMR (300 MHz, CDCl3) 7.14, 3.32, 2.73, 2.50, 2.35, 1.79, 1.55, 1.34, 1.12 and 0.97δ. cooled to 0° The solution is refluxed 4.5 hr quenched at 0° by adding 1.24 ml water, 1.24 ml 15% aqueous sodium hydride, and 3.71 ml water Filtration through a pad of diatomaceous earth and sodium sulfate evaporation of the solvent

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

Procedure: N-Ethyl-1-benzyl-4-piperidinyl carboxamide (EXAMPLE 174, 8.03 g, 32.60 mmol) is dissolved in THF and cooled to 0°. Lithium aluminum hydride (1M in THF) is added dropwise. The solution is refluxed 4.5 hr, then quenched at 0° by adding 1.24 ml water, 1.24 ml 15% aqueous sodium hydride, and 3.71 ml water. Filtration through a pad of diatomaceous earth and sodium sulfate and then evaporation of the solvent gives the title compound; NMR (300 MHz, CDCl3) 7.14, 3.32, 2.73, 2.50, 2.35, 1.79, 1.55, 1.34, 1.12 and 0.97δ. cooled to 0° The solution is refluxed 4.5 hr quenched at 0° by adding 1.24 ml water, 1.24 ml 15% aqueous sodium hydride, and 3.71 ml water Filtration through a pad of diatomaceous earth and sodium sulfate evaporation of the solvent

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

Procedure: 1-Benzyl-4-[(N-ethylamino)methyl]piperidine (EXAMPLE 261, 5.68 g) and 2-chloro-3-nitropyridine (3.87 g) are dissolved in 96 ml of acetonitrile and 4.05 g of solid potassium bicarbonate is added. The reaction is refluxed for 20 hr, cooled to 20°-25°, poured into water and extracted with ethyl acetate. The organic extracts are dried (sodium sulfate), and concentrated under reduced pressure. Purification by flash column chromatography (15% ethyl acetate/hexane to 80% ethyl acetate/hexane) gives the title compound, HRMS calcd. for C20H26N4O2 =354.2056, found=354.2045. The reaction is refluxed for 20 hr cooled to 20°-25° extracted with ethyl acetate The organic extracts are dried (sodium sulfate) concentrated under reduced pressure Purification by flash column chromatography (15% ethyl acetate/hexane to 80% ethyl acetate/hexane)

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

Procedure: 1-Benzyl-4-[N-ethylamino]methylpiperidine (EXAMPLE 175, 7.59, 32.64 mmol), 2-chloro-3-nitropyridine (5.17 g, 32.64 mmol) and potassium carbonate (5.41 g, 39.17 mmol) in acetonitrile (0.25M) are refluxed 48 hr. The mixture is diluted with water and extracted with ethyl acetate and then dichloromethane. The combined extracts are dried over sodium sulfate, concentrated and chromatographed (silica gel column, 300 g; eluting with 15-80% ethyl acetate/hexane), to give the title compound, NMR (300 MHz, CD3OD) 8.43, 8.20, 7.42, 6.90, 3.61, 3.52, 3.49, 3.00, 2.10, 1.80, 1.37 and 1.25δ. extracted with ethyl acetate The combined extracts are dried over sodium sulfate concentrated chromatographed (silica gel column, 300 g; eluting with 15-80% ethyl acetate/hexane)

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

Procedure: N-Ethyl-1-benzyl-4-piperidinyl carboxamide (EXAMPLE 174, 8.03 g, 32.60 mmol) is dissolved in THF and cooled to 0°. Lithium aluminum hydride (1M in THF) is added dropwise. The solution is refluxed 4.5 hr, then quenched at 0° by adding 1.24 ml water, 1.24 ml 15% aqueous sodium hydride, and 3.71 ml water. Filtration through a pad of diatomaceous earth and sodium sulfate and then evaporation of the solvent gives the title compound; NMR (300 MHz, CDCl3) 7.14, 3.32, 2.73, 2.50, 2.35, 1.79, 1.55, 1.34, 1.12 and 0.97δ. cooled to 0° The solution is refluxed 4.5 hr quenched at 0° by adding 1.24 ml water, 1.24 ml 15% aqueous sodium hydride, and 3.71 ml water Filtration through a pad of diatomaceous earth and sodium sulfate evaporation of the solvent