5-Amino-hexahydro-cyclopenta[c]pyrrole-2-carboxylic acid tert-butyl ester

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2,4-dichloro-5-methylpyrimidine (2.00 g, 12.3 mmol) and tert-butyl 5-aminohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (4.64 g, 20.5 mmol) in EtOH (25 mL) was added Et3N (2.62 g, 25.9 mmol). The reaction mixture was stirred at 50° C. overnight and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/2) to give the title compound as yellow oil (2.42 g, 55.9%). concentrated in vacuo The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/2)

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2,4-dichloro-5-methylpyrimidine (2.00 g, 12.3 mmol) and tert-butyl 5-aminohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (4.64 g, 20.5 mmol) in EtOH (25 mL) was added Et3N (2.62 g, 25.9 mmol). The reaction mixture was stirred at 50° C. overnight and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/2) to give the title compound as yellow oil (2.42 g, 55.9%). concentrated in vacuo The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/2)

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

实验步骤: To a solution of 2,4,5-trichloropyrimidine (1.46 g, 7.96 mmol) and tert-butyl 5-aminohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (3.11 g, 13.74 mmol) in EtOH (60 mL) was added Et3N (2.21 g, 21.84 mmol) and the reaction mixture was stirred at rt overnight and then concentrated in vacuo. The residue was dissolved in a mixture of EtOAc (50 mL) and water (50 mL), and extracted with EtOAc (150 mL×3). The combined organic phases were washed with brine (150 mL), dried over anhydrous Na2SO4, then concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/5) to give the title compound as a pale yellow solid (2.97 g, 100%). concentrated in vacuo The residue was dissolved in a mixture of EtOAc (50 mL) and water (50 mL) extracted with EtOAc (150 mL×3) The combined organic phases were washed with brine (150 mL) dried over anhydrous Na2SO4 concentrated in vacuo The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/5)

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of tert-butyl 5-(benzylamino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (6.50 g, 20.5 mmol) and AcOH (1.23 g, 20.5 mmol) in MeOH (150 mL) was added Pd(OH)2/C (10% wt, 1.00 g), and the suspension was stirred at 40° C. under H2 atmosphere overnight. The mixture was filtered through a pad of Celite and then concentrated in vacuo. The residue was dissolved in saturated NaHCO3 solution (70 mL) and extracted with DCM (100 mL×3). The combined organic phases were washed with brine (100 mL×3), dried over anhydrous Na2SO4, then filtered and concentrated in vacuo to give the title compound as a yellow solid (4.00 g, 86.2%). The mixture was filtered through a pad of Celite concentrated in vacuo The residue was dissolved in saturated NaHCO3 solution (70 mL) extracted with DCM (100 mL×3) The combined organic phases were washed with brine (100 mL×3) dried over anhydrous Na2SO4 filtered concentrated in vacuo

反应条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of tert-butyl 5-aminohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (1.0 g, 4.4 mmol) and triethylorothoformate (4.4 mL, 26.4 mmol) in acetic acid (20 mL) was added sodium azide (1.7 g, 26.4 mmol) and the resulting mixture was set under inert atmosphere. The mixture was heated at 100° C. for 4 h and then cooled to RT at which time the volatiles were removed in vacuo. The residue was taken up in ethyl acetate (100 mL) and washed with aqueous sodium bicarbonate solution, followed by brine. The organics were dried over sodium sulfate, filtered, and concentrate to dryness under vacuum. The residue was placed in the refrigerator overnight and the next day a solid white precipitate was observed. The precipitate was triturated with hexane and the solvent was carefully decanted to give the pure product (675 mg, 55%) as a white solid. EST-MS calculated for C13H21N5O2: Exact Mass: 279.28. Found 280.28 (MH) and 302.27 (MNa)+. cooled to RT at which time the volatiles were removed in vacuo washed with aqueous sodium bicarbonate solution The organics were dried over sodium sulfate filtered concentrate to dryness under vacuum was placed in the refrigerator overnight The precipitate was triturated with hexane the solvent was carefully decanted

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

实验步骤: To a solution of 2,4-dichloropyrimidine-5-carbonitrile (600 mg, 3.4485 mmol) and tert-butyl 5-aminohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (936.8 mg, 4.139 mmol) in ethanol (50 mL) was added N,N-diethylethanamine (698.5 mg, 6.903 mmol). The mixture was stirred at rt for 3 h. Then it was concentrated under vacuo, and the residue was purified by silica gel column chromatography (PE/EtOAc (v/v)=5/1) to give the title product as yellow oil (332.5 mg, 26.50%). Then it was concentrated under vacuo the residue was purified by silica gel column chromatography (PE/EtOAc (v/v)=5/1)

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2,4-dichloro-5-methyl-pyrimidine (2.00 g, 12.3 mmol) and tert-butyl 5-aminohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (4.64 g, 20.5 mmol) in EtOH (25 mL) was added Et3N (2.62 g, 25.9 mmol). The reaction mixture was stirred at 50° C. overnight and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/2) to give the title compound as yellow oil (2.42 g, 55.9%). concentrated in vacuo The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/2)

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

实验步骤: To a solution of 2,4,5-trichloropyrimidine (1.46 g, 7.96 mmol) and tert-butyl 5-aminohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (3.11 g, 13.74 mmol) in EtOH (60 mL) was added Et3N (2.21 g, 21.84 mmol) and the reaction mixture was stirred at rt overnight and then concentrated in vacuo. The residue was dissolved in a mixture of EtOAc (50 mL) and water (50 mL), and extracted with EtOAc (150 mL×3). The combined organic phases were washed with brine (150 mL), dried over anhydrous Na2SO4, then concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/5) to give the title compound as a pale yellow solid (2.97 g, 100%). concentrated in vacuo The residue was dissolved in a mixture of EtOAc (50 mL) and water (50 mL) extracted with EtOAc (150 mL×3) The combined organic phases were washed with brine (150 mL) dried over anhydrous Na2SO4 concentrated in vacuo The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/5)

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2,4-dichloro-5-methylpyrimidine (2.00 g, 12.3 mmol) and tert-butyl 5-aminohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (4.64 g, 20.5 mmol) in EtOH (25 mL) was added Et3N (2.62 g, 25.9 mmol). The reaction mixture was stirred at 50° C. overnight and concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/2) to give the title compound as yellow oil (2.42 g, 55.9%). concentrated in vacuo The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/2)

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

实验步骤: To a solution of 2,4,5-trichloropyrimidine (1.46 g, 7.96 mmol) and tert-butyl 5-aminohexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (3.11 g, 13.74 mmol) in EtOH (60 mL) was added Et3N (2.21 g, 21.84 mmol) and the reaction mixture was stirred at rt overnight and then concentrated in vacuo. The residue was dissolved in a mixture of EtOAc (50 mL) and water (50 mL), and extracted with EtOAc (150 mL×3). The combined organic phases were washed with brine (150 mL), dried over anhydrous Na2SO4, then concentrated in vacuo. The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/5) to give the title compound as a pale yellow solid (2.97 g, 100%). concentrated in vacuo The residue was dissolved in a mixture of EtOAc (50 mL) and water (50 mL) extracted with EtOAc (150 mL×3) The combined organic phases were washed with brine (150 mL) dried over anhydrous Na2SO4 concentrated in vacuo The residue was purified by silica gel column chromatography (EtOAc/PE (v/v)=1/5)

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of tert-butyl 5-(benzylamino)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate (6.50 g, 20.5 mmol) and AcOH (1.23 g, 20.5 mmol) in MeOH (150 mL) was added Pd(OH)2/C (10% wt, 1.00 g), and the suspension was stirred at 40° C. under H2 atmosphere overnight. The mixture was filtered through a pad of Celite and then concentrated in vacuo. The residue was dissolved in saturated NaHCO3 solution (70 mL) and extracted with DCM (100 mL×3). The combined organic phases were washed with brine (100 mL×3), dried over anhydrous Na2SO4, then filtered and concentrated in vacuo to give the title compound as a yellow solid (4.00 g, 86.2%). The mixture was filtered through a pad of Celite concentrated in vacuo The residue was dissolved in saturated NaHCO3 solution (70 mL) extracted with DCM (100 mL×3) The combined organic phases were washed with brine (100 mL×3) dried over anhydrous Na2SO4 filtered concentrated in vacuo