tert-butyl (1R,3S,4S)-3-(aminomethyl)-2-azabicyclo[2.2.1]heptane-2-carboxylate

反応条件: temp:138.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Bromo-2-chloro-pyrimidine (8.62 mmol) is added to a solution of (1R,3S,4S)-3-aminomethyl-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (6.63 mmol) in o-xylene (25 mL). K2CO3 (20.0 mmol) and DIPEA (19.9 mmol) are added successively and the mixture is heated to 138° C. for 16 h. The mixture is cooled to rt and filtered. The residue is washed with DCM and the combined filtrates are concentrated in vacuo to give the desired product which is used without further purification. LC-MS: tR=1.09 min; [M+H]+=383.3. The mixture is cooled to rt filtered The residue is washed with DCM the combined filtrates are concentrated in vacuo

反応条件: temp:138.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Bromo-2-chloro-pyrimidine (8.62 mmol) is added to a solution of (1R,3S,4S)-3-aminomethyl-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (6.63 mmol) in o-xylene (25 mL). K2CO3 (20.0 mmol) and DIPEA (19.9 mmol) are added successively and the mixture is heated to 138° C. for 16 h. The mixture is cooled to rt and filtered. The residue is washed with DCM and the combined filtrates are concentrated in vacuo to give the desired product which is used without further purification. LC-MS: tR=1.09 min; [M+H]+=383.3. The mixture is cooled to rt filtered The residue is washed with DCM the combined filtrates are concentrated in vacuo

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

実験手順: Ethyl trifluoroacetate (12.2 mmol, 1.30 eq) is added to a solution of (1R,3S,4S)-3-aminomethyl-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (9.42 mmol, 1.00 eq) and DIPEA (14.1 mmol, 1.50 eq) in THF (25 mL). After 50 min the mixture is concentrated in vacuo, diluted with TBME (100 mL) and washed twice with aq. citric acid (5%) and water respectively. The organic layer is dried over MgSO4 and concentrated in vacuo to give a crude product which is used without further purification. LC-MS (basic): tR=0.95 min; [M+H]+=323.2. After 50 min the mixture is concentrated in vacuo diluted with TBME (100 mL) washed twice with aq. citric acid (5%) and water respectively The organic layer is dried over MgSO4 concentrated in vacuo

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

実験手順: Ethyl trifluoroacetate (12.2 mmol, 1.30 eq) is added to a solution of (1R,3S,4S)-3-aminomethyl-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (9.42 mmol, 1.00 eq) and DIPEA (14.1 mmol, 1.50 eq) in THF (25 mL). After 50 min the mixture is concentrated in vacuo, diluted with TBME (100 mL) and washed twice with aq. citric acid (5%) and water respectively. The organic layer is dried over MgSO4 and concentrated in vacuo to give a crude product which is used without further purification. LC-MS (basic): tR=0.95 min; [M+H]+=323.2. After 50 min the mixture is concentrated in vacuo diluted with TBME (100 mL) washed twice with aq. citric acid (5%) and water respectively The organic layer is dried over MgSO4 concentrated in vacuo

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

実験手順: A solution of (1R,3S,4S)-3-(benzylamino-methyl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (39.8 mmol) in EtOH (120 mL) is treated with Pd/C (10%, 4.0 g) and stirred under a hydrogen atmosphere (7 bar) for 1 d. An additional amount of Pd/C (1.0 g) is added and the mixture is stirred for further 6 h under a hydrogen atmosphere (7 bar). After filtration through celite and removal of the solvents in vacuo the desired amine is obtained which is used without further purification. LC-MS (basic): tR=0.85 min; [M+H]+=227.3. the mixture is stirred for further 6 h under a hydrogen atmosphere (7 bar) After filtration through celite and removal of the solvents in vacuo the desired amine is obtained which is used without further purification

反応条件: temp:138.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5-Bromo-2-chloro-pyrimidine (8.62 mmol) is added to a solution of (1R,3S,4S)-3-aminomethyl-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (6.63 mmol) in o-xylene (25 mL). K2CO3 (20.0 mmol) and DIPEA (19.9 mmol) are added successively and the mixture is heated to 138° C. for 16 h. The mixture is cooled to rt and filtered. The residue is washed with DCM and the combined filtrates are concentrated in vacuo to give the desired product which is used without further purification. LC-MS: tR=1.09 min; [M+H]+=383.3. The mixture is cooled to rt filtered The residue is washed with DCM the combined filtrates are concentrated in vacuo

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

実験手順: Ethyl trifluoroacetate (12.2 mmol, 1.30 eq) is added to a solution of (1R,3S,4S)-3-aminomethyl-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (9.42 mmol, 1.00 eq) and DIPEA (14.1 mmol, 1.50 eq) in THF (25 mL). After 50 min the mixture is concentrated in vacuo, diluted with TBME (100 mL) and washed twice with aq. citric acid (5%) and water respectively. The organic layer is dried over MgSO4 and concentrated in vacuo to give a crude product which is used without further purification. LC-MS (basic): tR=0.95 min; [M+H]+=323.2. After 50 min the mixture is concentrated in vacuo diluted with TBME (100 mL) washed twice with aq. citric acid (5%) and water respectively The organic layer is dried over MgSO4 concentrated in vacuo

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

実験手順: A solution of (1R,3S,4S)-3-(benzylamino-methyl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (39.8 mmol) in EtOH (120 mL) is treated with Pd/C (10%, 4.0 g) and stirred under a hydrogen atmosphere (7 bar) for 1 d. An additional amount of Pd/C (1.0 g) is added and the mixture is stirred for further 6 h under a hydrogen atmosphere (7 bar). After filtration through celite and removal of the solvents in vacuo the desired amine is obtained which is used without further purification. LC-MS (basic): tR=0.85 min; [M+H]+=227.3. the mixture is stirred for further 6 h under a hydrogen atmosphere (7 bar) After filtration through celite and removal of the solvents in vacuo the desired amine is obtained which is used without further purification