2-N-(氧杂-4-基)苯-1,2-二胺

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

实验步骤: Et3N (2.6 mL, 18.9 mmol) was added to a stirred mixture of N-(tetrahydropyran-4-yl)benzene-1,2-diamine (1.21 g, 6.29 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (1.31 g, 6.92 mmol), HOAt (0.94 g, 6.92 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.33 g, 6.92 mmol) in anhydrous DCM (30 mL) at 0° C. under a nitrogen atmosphere. Stirring was continued for 10 min at 0° C. then the mixture was slowly warmed to RT and stirred at RT for 4 h. The reaction mixture was partitioned between DCM and a saturated solution of NaHCO3. The aqueous phase was further extracted with DCM and the combined organic layers were then washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-4% 2M NH3/MeOH in DCM) affording {(S)-1-[2-(Tetrahydropyran-4-ylamino)phenylcarbamoyl]ethyl}carbamic acid tertbutyl ester as a white solid (1.91 g, 83%). LCMS: RT 2.78 min [M+H-tBu]+ 308.1. stirred at RT for 4 h The reaction mixture was partitioned between DCM The aqueous phase was further extracted with DCM the combined organic layers were then washed with brine dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, gradient 0-4% 2M NH3/MeOH in DCM)

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

实验步骤: Et3N (2.6 mL, 18.9 mmol) was added to a stirred mixture of N-(tetrahydropyran-4-yl)benzene-1,2-diamine (1.21 g, 6.29 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (1.31 g, 6.92 mmol), HOAt (0.94 g, 6.92 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.33 g, 6.92 mmol) in anhydrous DCM (30 mL) at 0° C. under a nitrogen atmosphere. Stirring was continued for 10 min at 0° C. then the mixture was slowly warmed to RT and stirred at RT for 4 h. The reaction mixture was partitioned between DCM and a saturated solution of NaHCO3. The aqueous phase was further extracted with DCM and the combined organic layers were then washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-4% 2M NH3/MeOH in DCM) affording {(S)-1-[2-(Tetrahydropyran-4-ylamino)phenylcarbamoyl]ethyl}carbamic acid tertbutyl ester as a white solid (1.91 g, 83%). LCMS: RT 2.78 min [M+H-tBu]+ 308.1. stirred at RT for 4 h The reaction mixture was partitioned between DCM The aqueous phase was further extracted with DCM the combined organic layers were then washed with brine dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, gradient 0-4% 2M NH3/MeOH in DCM)

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

实验步骤: A mixture of (2-nitrophenyl)(tetrahydropyran-4-yl)amine (1.58 g, 7.09 mmol) and 10% Pd/C (400 mg) in EtOAc (30 mL) was degassed with a stream of nitrogen and stirred at RT under a hydrogen atmosphere for 3 days. The suspension was then filtered through a pad of celite and the filtrate was concentrated in vacuo affording N-(Tetrahydropyran-4-yl)benzene-1,2-diamine as a colourless oil (quantitative). 1H NMR (CDCl3, 400 MHz): δ 6.83-6.64 (4H, m), 4.01 (2H, d, J=11.69 Hz), 3.57-3.41 (3H, m), 3.40-3.19 (3H, bs), 2.08-1.99 (2H, m), 1.59-1.46 (2H, m). was degassed with a stream of nitrogen The suspension was then filtered through a pad of celite 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 mixture of (2-nitrophenyl)(tetrahydropyran-4-yl)amine (1.58 g, 7.09 mmol) and 10% Pd/C (400 mg) in EtOAc (30 mL) was degassed with a stream of nitrogen and stirred at RT under a hydrogen atmosphere for 3 days. The suspension was then filtered through a pad of celite and the filtrate was concentrated in vacuo affording N-(Tetrahydropyran-4-yl)benzene-1,2-diamine as a colourless oil (quantitative). 1H NMR (CDCl3, 400 MHz): δ 6.83-6.64 (4H, m), 4.01 (2H, d, J=11.69 Hz), 3.57-3.41 (3H, m), 3.40-3.19 (3H, bs), 2.08-1.99 (2H, m), 1.59-1.46 (2H, m). was degassed with a stream of nitrogen The suspension was then filtered through a pad of celite 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: Et3N (2.6 mL, 18.9 mmol) was added to a stirred mixture of N-(tetrahydropyran-4-yl)benzene-1,2-diamine (1.21 g, 6.29 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (1.31 g, 6.92 mmol), HOAt (0.94 g, 6.92 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.33 g, 6.92 mmol) in anhydrous DCM (30 mL) at 0° C. under a nitrogen atmosphere. Stirring was continued for 10 min at 0° C. then the mixture was slowly warmed to RT and stirred at RT for 4 h. The reaction mixture was partitioned between DCM and a saturated solution of NaHCO3. The aqueous phase was further extracted with DCM and the combined organic layers were then washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-4% 2M NH3/MeOH in DCM) affording {(S)-1-[2-(Tetrahydropyran-4-ylamino)phenylcarbamoyl]ethyl}carbamic acid tertbutyl ester as a white solid (1.91 g, 83%). LCMS: RT 2.78 min [M+H-tBu]+ 308.1. stirred at RT for 4 h The reaction mixture was partitioned between DCM The aqueous phase was further extracted with DCM the combined organic layers were then washed with brine dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, gradient 0-4% 2M NH3/MeOH in DCM)

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

实验步骤: A mixture of (2-nitrophenyl)(tetrahydropyran-4-yl)amine (1.58 g, 7.09 mmol) and 10% Pd/C (400 mg) in EtOAc (30 mL) was degassed with a stream of nitrogen and stirred at RT under a hydrogen atmosphere for 3 days. The suspension was then filtered through a pad of celite and the filtrate was concentrated in vacuo affording N-(Tetrahydropyran-4-yl)benzene-1,2-diamine as a colourless oil (quantitative). 1H NMR (CDCl3, 400 MHz): δ 6.83-6.64 (4H, m), 4.01 (2H, d, J=11.69 Hz), 3.57-3.41 (3H, m), 3.40-3.19 (3H, bs), 2.08-1.99 (2H, m), 1.59-1.46 (2H, m). was degassed with a stream of nitrogen The suspension was then filtered through a pad of celite 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: Et3N (2.6 mL, 18.9 mmol) was added to a stirred mixture of N-(tetrahydropyran-4-yl)benzene-1,2-diamine (1.21 g, 6.29 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (1.31 g, 6.92 mmol), HOAt (0.94 g, 6.92 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.33 g, 6.92 mmol) in anhydrous DCM (30 mL) at 0° C. under a nitrogen atmosphere. Stirring was continued for 10 min at 0° C. then the mixture was slowly warmed to RT and stirred at RT for 4 h. The reaction mixture was partitioned between DCM and a saturated solution of NaHCO3. The aqueous phase was further extracted with DCM and the combined organic layers were then washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-4% 2M NH3/MeOH in DCM) affording {(S)-1-[2-(Tetrahydropyran-4-ylamino)phenylcarbamoyl]ethyl}carbamic acid tertbutyl ester as a white solid (1.91 g, 83%). LCMS: RT 2.78 min [M+H-tBu]+ 308.1. stirred at RT for 4 h The reaction mixture was partitioned between DCM The aqueous phase was further extracted with DCM the combined organic layers were then washed with brine dried (Na2SO4) concentrated in vacuo The resulting residue was purified by column chromatography (Si—PCC, gradient 0-4% 2M NH3/MeOH in DCM)

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

实验步骤: A mixture of (2-nitrophenyl)(tetrahydropyran-4-yl)amine (1.58 g, 7.09 mmol) and 10% Pd/C (400 mg) in EtOAc (30 mL) was degassed with a stream of nitrogen and stirred at RT under a hydrogen atmosphere for 3 days. The suspension was then filtered through a pad of celite and the filtrate was concentrated in vacuo affording N-(Tetrahydropyran-4-yl)benzene-1,2-diamine as a colourless oil (quantitative). 1H NMR (CDCl3, 400 MHz): δ 6.83-6.64 (4H, m), 4.01 (2H, d, J=11.69 Hz), 3.57-3.41 (3H, m), 3.40-3.19 (3H, bs), 2.08-1.99 (2H, m), 1.59-1.46 (2H, m). was degassed with a stream of nitrogen The suspension was then filtered through a pad of celite the filtrate was concentrated in vacuo