(3R)-3-amino-1-methylpiperidin-2-one

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

実験手順: To a solution of 2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (150 mg, 0.45 mmol) and (R)-3-amino-1-methyl-piperidin-2-one (115 mg, 0.90 mmol) in DMF (2.4 mL) at room temperature was added triethylamine (0.19 mL, 1.35 mmol) and PyBOP (257 mg, 0.50 mmol). The reaction mixture was stirred overnight then diluted with EtOAc (30 mL) and washed with water (4×30 mL). The combined organic extracts were dried (Na2SO4) and evaporated under vacuum. The crude residue was purified by SiO2 column chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3) to give 149 mg (74%) of 2-cyclopropyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-oxo-piperidin-3-yl)-amide as a colorless viscous oil. washed with water (4×30 mL) The combined organic extracts were dried (Na2SO4) evaporated under vacuum The crude residue was purified by SiO2 column chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3)

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

実験手順: To a solution of 2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (150 mg, 0.45 mmol) and (R)-3-amino-1-methyl-piperidin-2-one (115 mg, 0.90 mmol) in DMF (2.4 mL) at room temperature was added triethylamine (0.19 mL, 1.35 mmol) and PyBOP (257 mg, 0.50 mmol). The reaction mixture was stirred overnight then diluted with EtOAc (30 mL) and washed with water (4×30 mL). The combined organic extracts were dried (Na2SO4) and evaporated under vacuum. The crude residue was purified by SiO2 column chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3) to give 149 mg (74%) of 2-cyclopropyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-oxo-piperidin-3-yl)-amide as a colorless viscous oil. washed with water (4×30 mL) The combined organic extracts were dried (Na2SO4) evaporated under vacuum The crude residue was purified by SiO2 column chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3)

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

実験手順: A solution of (R)-tert-butyl 1-methyl-2-oxopiperidin-3-ylcarbamate (310 mg, 1.36 mmol) in 2,2,2-trifluoroethanol (4.95 mL, 67.9 mmol) was heated at 150° C. for 3 h under microwave assisted conditions. The solvent was evaporated to dryness and the crude residue was purified by SiO2 chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3) to give 120 mg (69%) of (R)-3-amino-1-methyl-piperidin-2-one as a light yellow oil. The solvent was evaporated to dryness the crude residue was purified by SiO2 chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3)

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

実験手順: A solution of (R)-tert-butyl 1-methyl-2-oxopiperidin-3-ylcarbamate (310 mg, 1.36 mmol) in 2,2,2-trifluoroethanol (4.95 mL, 67.9 mmol) was heated at 150° C. for 3 h under microwave assisted conditions. The solvent was evaporated to dryness and the crude residue was purified by SiO2 chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3) to give 120 mg (69%) of (R)-3-amino-1-methyl-piperidin-2-one as a light yellow oil. The solvent was evaporated to dryness the crude residue was purified by SiO2 chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3)

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

実験手順: To a solution of 2-cyclopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (150 mg, 0.45 mmol) and (R)-3-amino-1-methyl-piperidin-2-one (115 mg, 0.90 mmol) in DMF (2.4 mL) at room temperature was added triethylamine (0.19 mL, 1.35 mmol) and PyBOP (257 mg, 0.50 mmol). The reaction mixture was stirred overnight then diluted with EtOAc (30 mL) and washed with water (4×30 mL). The combined organic extracts were dried (Na2SO4) and evaporated under vacuum. The crude residue was purified by SiO2 column chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3) to give 149 mg (74%) of 2-cyclopropyl-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-1-methyl-2-oxo-piperidin-3-yl)-amide as a colorless viscous oil. washed with water (4×30 mL) The combined organic extracts were dried (Na2SO4) evaporated under vacuum The crude residue was purified by SiO2 column chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3)

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

実験手順: A solution of (R)-tert-butyl 1-methyl-2-oxopiperidin-3-ylcarbamate (310 mg, 1.36 mmol) in 2,2,2-trifluoroethanol (4.95 mL, 67.9 mmol) was heated at 150° C. for 3 h under microwave assisted conditions. The solvent was evaporated to dryness and the crude residue was purified by SiO2 chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3) to give 120 mg (69%) of (R)-3-amino-1-methyl-piperidin-2-one as a light yellow oil. The solvent was evaporated to dryness the crude residue was purified by SiO2 chromatography (11 g, CH2Cl2/MeOH/NH4OH, 100:0:0 to 94:5.7:0.3)