4-benzylpiperazine-2,6-dione

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-benzylpiperazine-2,6-dione (which may be prepared in accordance with the experimental described in Example 4, step 1; 2.0 g, 9.8 mmol) in a mixture of methanol/H2O (65 mL/28 mL) were added a solution of HCl 1N in methanol (23.8 mL) and Pd/C (10% wet, 0.2% wt., 400 mg). The reaction mixture was degassed 3 times with hydrogen/vacuum prior to its overnight stirring under hydrogen (P=1 atm). The reaction mixture was then filtered on Clarcel® and washed with methanol. The filtrate was finally concentrated to dryness and the residue was precipitated from a mixture of methanol and ether. The title product was obtained as a beige solid (418 mg, 28%). The reaction mixture was degassed 3 times with hydrogen/vacuum The reaction mixture was then filtered on Clarcel® washed with methanol The filtrate was finally concentrated to dryness the residue was precipitated from a mixture of methanol and ether

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 2,2′-(benzylazanediyl)diacetic acid (5.0 g, 22.4 mmol) and ammonium formate (4.2 g, 67.2 mmol) in N,N-dimethylformamide (75 mL) was stirred to reflux (160° C.) for 2 days. After cooling to room temperature, the reaction mixture was diluted by successive addition of ethyl acetate (150 mL) and a saturated solution of sodium hydrogen carbonate (150 mL). The aqueous layer was extracted with ethyl acetate (2×150 mL) and the combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL), dried over sodium sulfate, filtered and concentrated under vacuum to give the title product as a yellow liquid (3.96 g, 87%). After cooling to room temperature The aqueous layer was extracted with ethyl acetate (2×150 mL) the combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL) dried over sodium sulfate filtered concentrated under vacuum

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspensiopn of 15 g (67 mmoles) of benzyliminodiacetic acid in 300 ml of CH2Cl2, 28 ml (201 mmoles) of triethylamine, 21.77 g (161 mmoles) of 1H-hydroxybenztriazole and 10.6 g (94 mmoles) of trifluoroacetamide are successively added and then 28.34 g (147.8 mmoles) of 1-[3(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride is added at 0° C. The reaction mixture is allowed to warm to ambient temperature and stirred for 18 hours. The reaction mixture is quenched with cold H2O and extracted with CH2Cl2. The combined extracts are washed with H2O brine, dried over MgSO4 and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (eluent: n-Hexane:AcOEt=2:1) to give 10 g of desired 4-benzyl-piperazine-2,6-dione in 73% yield. The reaction mixture is quenched with cold H2O extracted with CH2Cl2 The combined extracts are washed with H2O brine dried over MgSO4 concentrated under reduced pressure The residue is purified by silica gel column chromatography (eluent: n-Hexane:AcOEt=2:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspensiopn of 15 g (67 mmoles) of benzyliminodiacetic acid in 300 ml of CH2Cl2, 28 ml (201 mmoles) of triethylamine, 21.77 g (161 mmoles) of 1H-hydroxybenztriazole and 10.6 g (94 mmoles) of trifluoroacetamide are successively added and then 28.34 g (147.8 mmoles) of 1-[3(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride is added at 0° C. The reaction mixture is allowed to warm to ambient temperature and stirred for 18 hours. The reaction mixture is quenched with cold H2O and extracted with CH2Cl2. The combined extracts are washed with H2O brine, dried over MgSO4 and concentrated under reduced pressure. The residue is purified by silica gel column chromatography (eluent: n-Hexane:AcOEt=2:1) to give 10 g of desired 4-benzyl-piperazine-2,6-dione in 73% yield. The reaction mixture is quenched with cold H2O extracted with CH2Cl2 The combined extracts are washed with H2O brine dried over MgSO4 concentrated under reduced pressure The residue is purified by silica gel column chromatography (eluent: n-Hexane:AcOEt=2:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-benzylpiperazine-2,6-dione (which may be prepared in accordance with the experimental described in Example 4, step 1; 2.0 g, 9.8 mmol) in a mixture of methanol/H2O (65 mL/28 mL) were added a solution of HCl 1N in methanol (23.8 mL) and Pd/C (10% wet, 0.2% wt., 400 mg). The reaction mixture was degassed 3 times with hydrogen/vacuum prior to its overnight stirring under hydrogen (P=1 atm). The reaction mixture was then filtered on Clarcel® and washed with methanol. The filtrate was finally concentrated to dryness and the residue was precipitated from a mixture of methanol and ether. The title product was obtained as a beige solid (418 mg, 28%). The reaction mixture was degassed 3 times with hydrogen/vacuum The reaction mixture was then filtered on Clarcel® washed with methanol The filtrate was finally concentrated to dryness the residue was precipitated from a mixture of methanol and ether

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 2,2′-(benzylazanediyl)diacetic acid (5.0 g, 22.4 mmol) and ammonium formate (4.2 g, 67.2 mmol) in N,N-dimethylformamide (75 mL) was stirred to reflux (160° C.) for 2 days. After cooling to room temperature, the reaction mixture was diluted by successive addition of ethyl acetate (150 mL) and a saturated solution of sodium hydrogen carbonate (150 mL). The aqueous layer was extracted with ethyl acetate (2×150 mL) and the combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL), dried over sodium sulfate, filtered and concentrated under vacuum to give the title product as a yellow liquid (3.96 g, 87%). After cooling to room temperature The aqueous layer was extracted with ethyl acetate (2×150 mL) the combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL) dried over sodium sulfate filtered concentrated under vacuum

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 2,2′-(benzylazanediyl)diacetic acid (5.0 g, 22.4 mmol) and ammonium formate (4.2 g, 67.2 mmol) in N,N-dimethylformamide (75 mL) was stirred to reflux (160° C.) for 2 days. After cooling to room temperature, the reaction mixture was diluted by successive addition of ethyl acetate (150 mL) and a saturated solution of sodium hydrogen carbonate (150 mL). The aqueous layer was extracted with ethyl acetate (2×150 mL) and the combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL), dried over sodium sulfate, filtered and concentrated under vacuum to give the title product as a yellow liquid (3.96 g, 87%). After cooling to room temperature The aqueous layer was extracted with ethyl acetate (2×150 mL) the combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL) dried over sodium sulfate filtered concentrated under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-benzylpiperazine-2,6-dione (which may be prepared in accordance with the experimental described in Example 4, step 1; 2.0 g, 9.8 mmol) in a mixture of methanol/H2O (65 mL/28 mL) were added a solution of HCl 1N in methanol (23.8 mL) and Pd/C (10% wet, 0.2% wt., 400 mg). The reaction mixture was degassed 3 times with hydrogen/vacuum prior to its overnight stirring under hydrogen (P=1 atm). The reaction mixture was then filtered on Clarcel® and washed with methanol. The filtrate was finally concentrated to dryness and the residue was precipitated from a mixture of methanol and ether. The title product was obtained as a beige solid (418 mg, 28%). The reaction mixture was degassed 3 times with hydrogen/vacuum The reaction mixture was then filtered on Clarcel® washed with methanol The filtrate was finally concentrated to dryness the residue was precipitated from a mixture of methanol and ether

反応条件: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 2,2′-(benzylazanediyl)diacetic acid (5.0 g, 22.4 mmol) and ammonium formate (4.2 g, 67.2 mmol) in N,N-dimethylformamide (75 mL) was stirred to reflux (160° C.) for 2 days. After cooling to room temperature, the reaction mixture was diluted by successive addition of ethyl acetate (150 mL) and a saturated solution of sodium hydrogen carbonate (150 mL). The aqueous layer was extracted with ethyl acetate (2×150 mL) and the combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL), dried over sodium sulfate, filtered and concentrated under vacuum to give the title product as a yellow liquid (3.96 g, 87%). After cooling to room temperature The aqueous layer was extracted with ethyl acetate (2×150 mL) the combined organic phases were washed with a saturated solution of sodium chloride (3×100 mL) dried over sodium sulfate filtered concentrated under vacuum