(S)-1-苄基-3-乙基-2,5-哌嗪二酮

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of the product of example 69 part a) (5.68 g) in THF (30 ml) at 0° C. was added LAH (100 ml, 1.0M in THF) dropwise. The resulting solution was heated at reflux overnight. The reaction mixture was cooled to RT and quenched by cautious sequential addition of water (3.8 ml), 15% aq NaOH (3.8 ml), and water (11.4 ml). The precipitous solution was diluted with EtOAc and filtered through Celite. The residue was washed with EtOAc (3×100 ml) and the combined organics concentrated in vacuo. The crude product was dissolved in DCM, filtered through Celite and the solvent removed in vacuo to give the sub-titled product as a yellow oil (4.74 g). The resulting solution was heated at reflux overnight quenched by cautious sequential addition of water (3.8 ml), 15% aq NaOH (3.8 ml), and water (11.4 ml) The precipitous solution was diluted with EtOAc filtered through Celite The residue was washed with EtOAc (3×100 ml) the combined organics concentrated in vacuo The crude product was dissolved in DCM filtered through Celite the solvent removed in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of DCC (5.07 g) in DCM (140 mL) at 0° C. was added N—BOC-L-□-aminobutyric acid (5 g) followed by ethyl JV-benzylglycinate (4.6 mL) dropwise. The resulting solution was stirred at 0° C. for 2 h and RT 1 h, filtered and the concentrated to give an oil. This was dissolved in DCM (100 mL) and TFA (100 ml) and stirred for 1 h. The solution was concentrated under reduced pressure. The residue was stirred in saturated aq NaHCO3 (125 ml) and EtOAc (125 ml) for 6 h. The organics were separated, dried (Na2SO4), and concentrated to give the sub title compound as a white solid. (5.68 g). filtered the concentrated to give an oil The solution was concentrated under reduced pressure The residue was stirred in saturated aq NaHCO3 (125 ml) EtOAc (125 ml) for 6 h The organics were separated dried (Na2SO4) concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 8.1 gm (34.9 mmol) 2(S)-ethyl-4-benzyl-3,6-dioxopiperazine in 50 mL tetrahydrofuran was added dropwise via addition funnel to a solution of 75 mL (75 mMol) lithium aluminum hydride (1M in tetrahydrofuran) and the mixture was heated at reflux for 2.5 h. The reaction was then cooled in an ice bath and was treated sequentially with 3 mL deionized water, 3 mL 5N sodium hydroxide, and 9 mL deionized water. The resulting slurry was allowed to stir for 1 hour and was then filtered. The recovered salts were rinsed with 100 mL tetrahydrofuran and 100 mL dichloromethane. The filtrate was concentrated in vacuo to afford 7.03 g (99%) of the desired piperazine. the mixture was heated at reflux for 2.5 h The reaction was then cooled in an ice bath was treated sequentially with 3 mL was then filtered The recovered salts were rinsed with 100 mL tetrahydrofuran and 100 mL dichloromethane The filtrate was concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 8.1 gm (34.9 mmol) 2(S)-ethyl-4-benzyl-3,6-dioxopiperazine in 50 mL tetrahydrofuran was added dropwise via addition funnel to a solution of 75 mL (75 mMol) lithium aluminum hydride (1M in tetrahydrofuran) and the mixture was heated at reflux for 2.5 h. The reaction was then cooled in an ice bath and was treated sequentially with 3 mL deionized water, 3 mL 5N sodium hydroxide, and 9 mL deionized water. The resulting slurry was allowed to stir for 1 hour and was then filtered. The recovered salts were rinsed with 100 mL tetrahydrofuran and 100 mL dichloromethane. The filtrate was concentrated in vacuo to afford 7.03 g (99%) of the desired piperazine. the mixture was heated at reflux for 2.5 h The reaction was then cooled in an ice bath was treated sequentially with 3 mL was then filtered The recovered salts were rinsed with 100 mL tetrahydrofuran and 100 mL dichloromethane The filtrate was concentrated in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of the product of example 69 part a) (5.68 g) in THF (30 ml) at 0° C. was added LAH (100 ml, 1.0M in THF) dropwise. The resulting solution was heated at reflux overnight. The reaction mixture was cooled to RT and quenched by cautious sequential addition of water (3.8 ml), 15% aq NaOH (3.8 ml), and water (11.4 ml). The precipitous solution was diluted with EtOAc and filtered through Celite. The residue was washed with EtOAc (3×100 ml) and the combined organics concentrated in vacuo. The crude product was dissolved in DCM, filtered through Celite and the solvent removed in vacuo to give the sub-titled product as a yellow oil (4.74 g). The resulting solution was heated at reflux overnight quenched by cautious sequential addition of water (3.8 ml), 15% aq NaOH (3.8 ml), and water (11.4 ml) The precipitous solution was diluted with EtOAc filtered through Celite The residue was washed with EtOAc (3×100 ml) the combined organics concentrated in vacuo The crude product was dissolved in DCM filtered through Celite the solvent removed in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of DCC (5.07 g) in DCM (140 mL) at 0° C. was added N—BOC-L-□-aminobutyric acid (5 g) followed by ethyl JV-benzylglycinate (4.6 mL) dropwise. The resulting solution was stirred at 0° C. for 2 h and RT 1 h, filtered and the concentrated to give an oil. This was dissolved in DCM (100 mL) and TFA (100 ml) and stirred for 1 h. The solution was concentrated under reduced pressure. The residue was stirred in saturated aq NaHCO3 (125 ml) and EtOAc (125 ml) for 6 h. The organics were separated, dried (Na2SO4), and concentrated to give the sub title compound as a white solid. (5.68 g). filtered the concentrated to give an oil The solution was concentrated under reduced pressure The residue was stirred in saturated aq NaHCO3 (125 ml) EtOAc (125 ml) for 6 h The organics were separated dried (Na2SO4) concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of the product of example 69 part a) (5.68 g) in THF (30 ml) at 0° C. was added LAH (100 ml, 1.0M in THF) dropwise. The resulting solution was heated at reflux overnight. The reaction mixture was cooled to RT and quenched by cautious sequential addition of water (3.8 ml), 15% aq NaOH (3.8 ml), and water (11.4 ml). The precipitous solution was diluted with EtOAc and filtered through Celite. The residue was washed with EtOAc (3×100 ml) and the combined organics concentrated in vacuo. The crude product was dissolved in DCM, filtered through Celite and the solvent removed in vacuo to give the sub-titled product as a yellow oil (4.74 g). The resulting solution was heated at reflux overnight quenched by cautious sequential addition of water (3.8 ml), 15% aq NaOH (3.8 ml), and water (11.4 ml) The precipitous solution was diluted with EtOAc filtered through Celite The residue was washed with EtOAc (3×100 ml) the combined organics concentrated in vacuo The crude product was dissolved in DCM filtered through Celite the solvent removed in vacuo

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of DCC (5.07 g) in DCM (140 mL) at 0° C. was added N—BOC-L-□-aminobutyric acid (5 g) followed by ethyl JV-benzylglycinate (4.6 mL) dropwise. The resulting solution was stirred at 0° C. for 2 h and RT 1 h, filtered and the concentrated to give an oil. This was dissolved in DCM (100 mL) and TFA (100 ml) and stirred for 1 h. The solution was concentrated under reduced pressure. The residue was stirred in saturated aq NaHCO3 (125 ml) and EtOAc (125 ml) for 6 h. The organics were separated, dried (Na2SO4), and concentrated to give the sub title compound as a white solid. (5.68 g). filtered the concentrated to give an oil The solution was concentrated under reduced pressure The residue was stirred in saturated aq NaHCO3 (125 ml) EtOAc (125 ml) for 6 h The organics were separated dried (Na2SO4) concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 8.1 gm (34.9 mmol) 2(S)-ethyl-4-benzyl-3,6-dioxopiperazine in 50 mL tetrahydrofuran was added dropwise via addition funnel to a solution of 75 mL (75 mMol) lithium aluminum hydride (1M in tetrahydrofuran) and the mixture was heated at reflux for 2.5 h. The reaction was then cooled in an ice bath and was treated sequentially with 3 mL deionized water, 3 mL 5N sodium hydroxide, and 9 mL deionized water. The resulting slurry was allowed to stir for 1 hour and was then filtered. The recovered salts were rinsed with 100 mL tetrahydrofuran and 100 mL dichloromethane. The filtrate was concentrated in vacuo to afford 7.03 g (99%) of the desired piperazine. the mixture was heated at reflux for 2.5 h The reaction was then cooled in an ice bath was treated sequentially with 3 mL was then filtered The recovered salts were rinsed with 100 mL tetrahydrofuran and 100 mL dichloromethane The filtrate was concentrated in vacuo