2-(4-甲基-1,4-二氮杂-1-基)乙醇

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

实验步骤: 2-(4-methylhomopiperazin-1-yl)ethanol from the previous step (2.77 g, 17.5 mmol) was dissolved in DCM (25 mL) and cooled to 0° C. NMM (2.00 mL, 18.4 mmol) and p-nitrophenyl chloroformate (3.71 g, 18.4 mmol) were added. The reaction mixture was stirred at 0° C. for 30 minutes and then at room temperature for 2 hours. A solution of 4-(4-methylphenyl)piperazine dihydrochloride (2.84 g, 11.4 mmol) and DIPEA (5.50 mL, 33.3 mmol) in DMF (40 mL) was then added. The reaction mixture was stirred at room temperature for 3 h and then concentrated in vacuo. The residue was dissolved in EtOAc (300 mL) and then washed sequentially with 1 M aq Na2CO3 solution (5×200 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 85:15 mixture of DCM:MeOH) followed by reverse phase HPLC (Advanced Chromatography Technologies ACE-122-1030 RP silica 100×30 mm column, packed with Ace 5 C8 (5 μm), Pore Size 100 Å, 30 mL/min, gradient of actonitrile in water, with 0.1% trifluoroacetic acid in each solvent, 8-38%). The resulting residue was dissolved in DCM (50 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give 2-(4-methyl-1,4-diazepan-1-yl)ethyl 4-(4-methylphenyl)piperazine-1-carboxylate (184 mg, 3.0%) as a pale yellow oil. at room temperature for 2 hours The reaction mixture was stirred at room temperature for 3 h concentrated in vacuo The residue was dissolved in EtOAc (300 mL) washed sequentially with 1 M aq Na2CO3 solution (5×200 mL) dried (MgSO4) concentrated in vacuo The residue was purified by normal phase column chromatography ( eluting with DCM followed by a 85:15 mixture of DCM The resulting residue was dissolved in DCM (50 mL) stirred with solid K2CO3 for 20 minutes filtered concentrated in vacuo

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

实验步骤: 1-Methylhomopiperazine (2.00 g, 17.5 mmol) and DIPEA (3.0 mL, 18.4 mmol) were dissolved in DMF (25 mL). 2-bromethanol (1.3 mL, 18.4 mmol) was added slowly over 5 minutes. The reaction mixture was stirred at 100° C. for 2 hours and then at room temperature for 48 hours and then concentrated in vacuo. The residue was dissolved in EtOAc (−300 mL) and then washed sequentially with 1M aq Na2CO3 solution (5×200 mL), dried (MgSO4) and concentrated in vacuo to give 2-(4-methylhomopiperazin-1-yl)ethanol (2.77 g, 100%) as a brown oil which was used without further purification. at room temperature for 48 hours concentrated in vacuo The residue was dissolved in EtOAc (−300 mL) washed sequentially with 1M aq Na2CO3 solution (5×200 mL) dried (MgSO4) concentrated in vacuo

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

实验步骤: 2-(4-methylhomopiperazin-1-yl)ethanol from the previous step (2.77 g, 17.5 mmol) was dissolved in DCM (25 mL) and cooled to 0° C. NMM (2.00 mL, 18.4 mmol) and p-nitrophenyl chloroformate (3.71 g, 18.4 mmol) were added. The reaction mixture was stirred at 0° C. for 30 minutes and then at room temperature for 2 hours. A solution of 4-(4-methylphenyl)piperazine dihydrochloride (2.84 g, 11.4 mmol) and DIPEA (5.50 mL, 33.3 mmol) in DMF (40 mL) was then added. The reaction mixture was stirred at room temperature for 3 h and then concentrated in vacuo. The residue was dissolved in EtOAc (300 mL) and then washed sequentially with 1 M aq Na2CO3 solution (5×200 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 85:15 mixture of DCM:MeOH) followed by reverse phase HPLC (Advanced Chromatography Technologies ACE-122-1030 RP silica 100×30 mm column, packed with Ace 5 C8 (5 μm), Pore Size 100 Å, 30 mL/min, gradient of actonitrile in water, with 0.1% trifluoroacetic acid in each solvent, 8-38%). The resulting residue was dissolved in DCM (50 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give 2-(4-methyl-1,4-diazepan-1-yl)ethyl 4-(4-methylphenyl)piperazine-1-carboxylate (184 mg, 3.0%) as a pale yellow oil. at room temperature for 2 hours The reaction mixture was stirred at room temperature for 3 h concentrated in vacuo The residue was dissolved in EtOAc (300 mL) washed sequentially with 1 M aq Na2CO3 solution (5×200 mL) dried (MgSO4) concentrated in vacuo The residue was purified by normal phase column chromatography ( eluting with DCM followed by a 85:15 mixture of DCM The resulting residue was dissolved in DCM (50 mL) stirred with solid K2CO3 for 20 minutes filtered concentrated in vacuo

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

实验步骤: 1-Methylhomopiperazine (2.00 g, 17.5 mmol) and DIPEA (3.0 mL, 18.4 mmol) were dissolved in DMF (25 mL). 2-bromethanol (1.3 mL, 18.4 mmol) was added slowly over 5 minutes. The reaction mixture was stirred at 100° C. for 2 hours and then at room temperature for 48 hours and then concentrated in vacuo. The residue was dissolved in EtOAc (−300 mL) and then washed sequentially with 1M aq Na2CO3 solution (5×200 mL), dried (MgSO4) and concentrated in vacuo to give 2-(4-methylhomopiperazin-1-yl)ethanol (2.77 g, 100%) as a brown oil which was used without further purification. at room temperature for 48 hours concentrated in vacuo The residue was dissolved in EtOAc (−300 mL) washed sequentially with 1M aq Na2CO3 solution (5×200 mL) dried (MgSO4) concentrated in vacuo

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

实验步骤: 2-(4-methylhomopiperazin-1-yl)ethanol from the previous step (2.77 g, 17.5 mmol) was dissolved in DCM (25 mL) and cooled to 0° C. NMM (2.00 mL, 18.4 mmol) and p-nitrophenyl chloroformate (3.71 g, 18.4 mmol) were added. The reaction mixture was stirred at 0° C. for 30 minutes and then at room temperature for 2 hours. A solution of 4-(4-methylphenyl)piperazine dihydrochloride (2.84 g, 11.4 mmol) and DIPEA (5.50 mL, 33.3 mmol) in DMF (40 mL) was then added. The reaction mixture was stirred at room temperature for 3 h and then concentrated in vacuo. The residue was dissolved in EtOAc (300 mL) and then washed sequentially with 1 M aq Na2CO3 solution (5×200 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 85:15 mixture of DCM:MeOH) followed by reverse phase HPLC (Advanced Chromatography Technologies ACE-122-1030 RP silica 100×30 mm column, packed with Ace 5 C8 (5 μm), Pore Size 100 Å, 30 mL/min, gradient of actonitrile in water, with 0.1% trifluoroacetic acid in each solvent, 8-38%). The resulting residue was dissolved in DCM (50 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give 2-(4-methyl-1,4-diazepan-1-yl)ethyl 4-(4-methylphenyl)piperazine-1-carboxylate (184 mg, 3.0%) as a pale yellow oil. at room temperature for 2 hours The reaction mixture was stirred at room temperature for 3 h concentrated in vacuo The residue was dissolved in EtOAc (300 mL) washed sequentially with 1 M aq Na2CO3 solution (5×200 mL) dried (MgSO4) concentrated in vacuo The residue was purified by normal phase column chromatography ( eluting with DCM followed by a 85:15 mixture of DCM The resulting residue was dissolved in DCM (50 mL) stirred with solid K2CO3 for 20 minutes filtered concentrated in vacuo

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

实验步骤: 2-(4-methylhomopiperazin-1-yl)ethanol from the previous step (2.77 g, 17.5 mmol) was dissolved in DCM (25 mL) and cooled to 0° C. NMM (2.00 mL, 18.4 mmol) and p-nitrophenyl chloroformate (3.71 g, 18.4 mmol) were added. The reaction mixture was stirred at 0° C. for 30 minutes and then at room temperature for 2 hours. A solution of 4-(4-methylphenyl)piperazine dihydrochloride (2.84 g, 11.4 mmol) and DIPEA (5.50 mL, 33.3 mmol) in DMF (40 mL) was then added. The reaction mixture was stirred at room temperature for 3 h and then concentrated in vacuo. The residue was dissolved in EtOAc (300 mL) and then washed sequentially with 1 M aq Na2CO3 solution (5×200 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by normal phase column chromatography (eluting with DCM, followed by a 85:15 mixture of DCM:MeOH) followed by reverse phase HPLC (Advanced Chromatography Technologies ACE-122-1030 RP silica 100×30 mm column, packed with Ace 5 C8 (5 μm), Pore Size 100 Å, 30 mL/min, gradient of actonitrile in water, with 0.1% trifluoroacetic acid in each solvent, 8-38%). The resulting residue was dissolved in DCM (50 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo to give 2-(4-methyl-1,4-diazepan-1-yl)ethyl 4-(4-methylphenyl)piperazine-1-carboxylate (184 mg, 3.0%) as a pale yellow oil. at room temperature for 2 hours The reaction mixture was stirred at room temperature for 3 h concentrated in vacuo The residue was dissolved in EtOAc (300 mL) washed sequentially with 1 M aq Na2CO3 solution (5×200 mL) dried (MgSO4) concentrated in vacuo The residue was purified by normal phase column chromatography ( eluting with DCM followed by a 85:15 mixture of DCM The resulting residue was dissolved in DCM (50 mL) stirred with solid K2CO3 for 20 minutes filtered concentrated in vacuo

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

实验步骤: 1-Methylhomopiperazine (2.00 g, 17.5 mmol) and DIPEA (3.0 mL, 18.4 mmol) were dissolved in DMF (25 mL). 2-bromethanol (1.3 mL, 18.4 mmol) was added slowly over 5 minutes. The reaction mixture was stirred at 100° C. for 2 hours and then at room temperature for 48 hours and then concentrated in vacuo. The residue was dissolved in EtOAc (−300 mL) and then washed sequentially with 1M aq Na2CO3 solution (5×200 mL), dried (MgSO4) and concentrated in vacuo to give 2-(4-methylhomopiperazin-1-yl)ethanol (2.77 g, 100%) as a brown oil which was used without further purification. at room temperature for 48 hours concentrated in vacuo The residue was dissolved in EtOAc (−300 mL) washed sequentially with 1M aq Na2CO3 solution (5×200 mL) dried (MgSO4) concentrated in vacuo