tert-butyl 4-(3-aminopropyl)piperidine-1-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution prepared by dissolving 3.59 g (10.66 mM) of 3-carbethoxy-5-chloromethylimidazo[1,2-a]pyridine sulfate, 3.10 g (12.79 mM) of 3-(1-tert-butoxycarbonylpiperidin-4-yl)-1-propylamine, and 5.94 ml (42.64 mM) of triethylamine in 30 ml of ethanol was refluxed for 5 hours. After completion of the reaction, the solvent was distilled off under reduced pressure and the residue was extracted with 100 ml of chloroform. The organic layer was washed with 100 ml of saturated aqueous NaCl solution and dried over MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform-methanol=50:1) to provide 2.55 g (yield 62.1%) of the title compound as yellow oil. A solution prepared was refluxed for 5 hours After completion of the reaction the solvent was distilled off under reduced pressure the residue was extracted with 100 ml of chloroform The organic layer was washed with 100 ml of saturated aqueous NaCl solution dried over MgSO4 the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (eluent: chloroform-methanol=50:1)

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

Procedure: A solution prepared by dissolving 3.59 g (10.66 mM) of 3-carbethoxy-5-chloromethylimidazo[1,2-a]pyridine sulfate, 3.10 g (12.79 mM) of 3-(1-tert-butoxycarbonylpiperidin-4-yl)-1-propylamine, and 5.94 ml (42.64 mM) of triethylamine in 30 ml of ethanol was refluxed for 5 hours. After completion of the reaction, the solvent was distilled off under reduced pressure and the residue was extracted with 100 ml of chloroform. The organic layer was washed with 100 ml of saturated aqueous NaCl solution and dried over MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform-methanol=50:1) to provide 2.55 g (yield 62.1%) of the title compound as yellow oil. A solution prepared was refluxed for 5 hours After completion of the reaction the solvent was distilled off under reduced pressure the residue was extracted with 100 ml of chloroform The organic layer was washed with 100 ml of saturated aqueous NaCl solution dried over MgSO4 the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (eluent: chloroform-methanol=50:1)

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

Procedure: A solution prepared by dissolving 3.59 g (10.66 mM) of 3-carbethoxy-5-chloromethylimidazo[1,2-a]pyridine sulfate, 3.10 g (12.79 mM) of 3-(1-tert-butoxycarbonylpiperidin-4-yl)-1-propylamine, and 5.94 ml (42.64 mM) of triethylamine in 30 ml of ethanol was refluxed for 5 hours. After completion of the reaction, the solvent was distilled off under reduced pressure and the residue was extracted with 100 ml of chloroform. The organic layer was washed with 100 ml of saturated aqueous NaCl solution and dried over MgSO4 and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: chloroform-methanol=50:1) to provide 2.55 g (yield 62.1%) of the title compound as yellow oil. A solution prepared was refluxed for 5 hours After completion of the reaction the solvent was distilled off under reduced pressure the residue was extracted with 100 ml of chloroform The organic layer was washed with 100 ml of saturated aqueous NaCl solution dried over MgSO4 the solvent was distilled off under reduced pressure The residue was purified by silica gel column chromatography (eluent: chloroform-methanol=50:1)

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Using the method of 2-{5-methyl-2-[2-(1-methylpiperidin-4-yl)-ethylamino]-pyrimidin-4-yl}-benzo[b]thiophene-6-carboxylic acid dimethylamide di-hydrochloride, the title compound is synthesized from [2-(2-chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophen-6-yl]-morpholin-4-ylmethanone and 4-(3-aminopropyl)-piperidine-1-carboxylic acid tert-butyl ester and isolated as yellow foam. ES+(m/z) 494 [M(free base)+H]. isolated as yellow foam

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

Procedure: Using the method of 2-[5-methyl-2-(2-piperidin-4-ylethylamino)-pyrimidin-4-yl]-benzo[b]thiophene-6-carboxylic acid methylamide di-hydrochloride, the title compound is synthesized from 2-(2-chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-6-carboxylic acid dimethylamide and 4-(3-aminopropyl)-piperidine-1-carboxylic acid tert-butyl ester and isolated as a foam. ES+(m/z) 438 [M(free base)+H]. isolated as a foam

Conditions: temp:97.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred mixture of 2-(2-chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid [bis-(4-methoxyphenyl)-methyl]-amide (1.14 g, 2.15 mmol), 4-(3-aminopropyl)-piperidine-1-carboxylic acid tert-butyl ester (1.04 g, 4.30 mmol) and diisopropylethylamine (1.12 mL, 6.45 mmol) in 1,4-dioxane (10 mL) is heated at 97° C. under a nitrogen atmosphere for 3 days. After concentration and subsequent chromatography on silica gel, eluting with MeOH in dichloromethane 0-2%, the desired product is obtained as a solid. The solid is suspended in dichloromethane (20 mL), followed by the successive addition of triethylsilane (1.5 mL) and TFA (5 mL). The resultant yellow solution is stirred for 2 hours. After concentration the solid is dissolved with stirring in MeOH (30 mL) and dichloromethane (30 mL) and the solution is treated in portions with 1.0 N LiOH (15 mL) to form a suspension. The suspension is concentrated at 45° C. under atmospheric pressure for 30 minutes, then methanol and dichloromethane are evaporated off in vacuo. The suspension is filtered and the yellow solid is dried under vacuum at 45° C. to provide the title compound (0.890 g, 100% yield). ES+(m/z) 410 [M+H]. After concentration and subsequent chromatography on silica gel eluting with MeOH in dichloromethane 0-2%

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

Procedure: 4-(3-Aminopropyl)-piperidine-1-carboxylic acid tert-butyl ester (0.818 g, 3.36 mmol) is added to a stirred suspension of 2-(2,5-dichloropyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid amide (0.436 g, 1.34 mmol) and diisopropylethylamine (0.70 mL, 4.0 mmol) in anhydrous 1,4-dioxane (8 mL) and dimethylacetamide (2 mL) at room temperature under nitrogen. The resultant mixture is heated in an oil bath at 95° C. for 7 hours. At room temperature the mixture is concentrated and chromatographed on silica gel, eluting with CH3OH in dichloromethane: 0-6%, to give 4-{3-[4-(4-carbamoyl-benzo[b]thiophen-2-yl)-5-chloro-pyrimidin-2-ylamino]-propyl}-piperazine-1-carboxylic acid tert-butyl ester (0.403 g) as a solid. At room temperature the mixture is concentrated chromatographed on silica gel eluting with CH3OH in dichloromethane

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

Procedure: Using the method of 2-[5-methyl-2-(2-piperidin-4-ylethylamino)-pyrimidin-4-yl]-benzo[b]thiophene-4-carboxylic acid cyclopropylamide, the title compound is synthesized from 2-(2-chloro-5-methylpyrimidin-4-yl)-benzo[b]thiophene-4-carboxylic acid cyclopropylamide and 4-(3-aminopropyl)-piperidine-1-carboxylic acid tert-butyl ester and isolated as a yellow solid. ES+(m/z) 450 [M+H]. isolated as a yellow solid