4-piperidin-4-ylbutanamide

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: tert-Butyl 4-(3-carbamoylpropyl)piperidine-1-carboxylate (0.38 g, 1.4 mmol, Production example 44-1) was dissolved in trifluoroacetic acid (2 ml) and the reaction mixture was stirred at room temperature for 20 minutes. The reaction mixture was concentrated under reduced pressure and then azeotropically distilled with toluene. The residue was partitioned between tetrahydrofuran and a saturated aqueous solution of sodium hydrogencarbonate; and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure; and the residue was purified by silica gel chromatography (Fuji Silysia NH, ethyl acetate-methanol system) to yield the title compound (0.55 g, quantitative) as pale yellow oil. The reaction mixture was concentrated under reduced pressure azeotropically distilled with toluene The residue was partitioned between tetrahydrofuran and the organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure and the residue was purified by silica gel chromatography (Fuji Silysia NH, ethyl acetate-methanol system)

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

Procedure: 4-(Piperidin-4-yl)butanamide (547 mg, 1.41 mmol) was dissolved in N,N-dimethylformamide (3 ml); phenyl N-(4-(1-(methylamino)carbonyl-1H-5-indolyloxy)-2-pyridyl)-N-(phenoxycarbonyl)carbamate (210 mg, 0.402 mmol, the product of Production example 5-2) was added thereto; and the reaction mixture was stirred at room temperature for 1.5 hour. The reaction mixture was partitioned between ethyl acetate and water; the organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure; and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol system). The obtained amorphous solid was crystallized by adding diethyl ether. After addition of a small amount of ethanol to make a suspension, this was diluted with hexane. After separation by filtration to obtain crystals, these were rinsed with diethyl ether and dried under aeration. Thus, the title compound was obtained as colorless crystals (157 mg, 0.328 mmol, 81.7%). The reaction mixture was partitioned between ethyl acetate and water the organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol system) The obtained amorphous solid was crystallized by adding diethyl ether After addition of a small amount of ethanol this was diluted with hexane After separation by filtration to obtain crystals these were rinsed with diethyl ether dried under aeration

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

Procedure: 4-(Piperidin-4-yl)butanamide (547 mg, 1.41 mmol) was dissolved in N,N-dimethylformamide (3 ml); phenyl N-(4-(1-(methylamino)carbonyl-1H-indol-5-yloxy)-pyridin-2-yl)-N-(phenoxycarbonyl)carbamate (210 mg, 0.402 mmol, the product of Production example 5-2) was added thereto; and the reaction mixture was stirred at room temperature for 1.5 hour. The reaction mixture was partitioned between ethyl acetate and water; the organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure; and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol system). The obtained amorphous solid was crystallized by adding diethyl ether. After addition of a small amount of ethanol to make a suspension, this was diluted with hexane. After separation by filtration to obtain crystals, these were rinsed with diethyl ether and dried under aeration. Thus, the title compound was obtained as colorless crystals (157 mg, 0.328 mmol, 81.7%). The reaction mixture was partitioned between ethyl acetate and water the organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol system) The obtained amorphous solid was crystallized by adding diethyl ether After addition of a small amount of ethanol this was diluted with hexane After separation by filtration to obtain crystals these were rinsed with diethyl ether dried under aeration

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

Procedure: 4-(Piperidin-4-yl)butanamide (547 mg, 1.41 mmol) was dissolved in N,N-dimethylformamide (3 ml); phenyl N-(4-(1-(methylamino)carbonyl-1H-indol-5-yloxy)-pyridin-2-yl)-N-(phenoxycarbonyl)carbamate (210 mg, 0.402 mmol, the product of Production example 5-2) was added thereto; and the reaction mixture was stirred at room temperature for 1.5 hour. The reaction mixture was partitioned between ethyl acetate and water; the organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure; and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol system). The obtained amorphous solid was crystallized by adding diethyl ether. After addition of a small amount of ethanol to make a suspension, this was diluted with hexane. After separation by filtration to obtain crystals, these were rinsed with diethyl ether and dried under aeration. Thus, the title compound was obtained as colorless crystals (157 mg, 0.328 mmol, 81.7%). The reaction mixture was partitioned between ethyl acetate and water the organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol system) The obtained amorphous solid was crystallized by adding diethyl ether After addition of a small amount of ethanol this was diluted with hexane After separation by filtration to obtain crystals these were rinsed with diethyl ether dried under aeration

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

Procedure: 4-(Piperidin-4-yl)butanamide (547 mg, 1.41 mmol) was dissolved in N,N-dimethylformamide (3 ml); phenyl N-(4-(1-(methylamino)carbonyl-1H-indol-5-yloxy)-pyridin-2-yl)-N-(phenoxycarbonyl)carbamate (210 mg, 0.402 mmol, the product of Production example 5-2) was added thereto; and the reaction mixture was stirred at room temperature for 1.5 hour. The reaction mixture was partitioned between ethyl acetate and water; the organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure; and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol system). The obtained amorphous solid was crystallized by adding diethyl ether. After addition of a small amount of ethanol to make a suspension, this was diluted with hexane. After separation by filtration to obtain crystals, these were rinsed with diethyl ether and dried under aeration. Thus, the title compound was obtained as colorless crystals (157 mg, 0.328 mmol, 81.7%). The reaction mixture was partitioned between ethyl acetate and water the organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol system) The obtained amorphous solid was crystallized by adding diethyl ether After addition of a small amount of ethanol this was diluted with hexane After separation by filtration to obtain crystals these were rinsed with diethyl ether dried under aeration

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

Procedure: The crude amide was dissolved in glacial acetic acid and hydrogenated at 60°/60 p.s.i. over a platinum oxide catalyst until uptake of hydrogen ceased. The catalyst was removed by filtration and the filtrate was evaporated in vacuo to give crude 4-(piperid-4-yl)butyramide as an oil. The catalyst was removed by filtration the filtrate was evaporated in vacuo