4-Methylmorpholine → 2-(4-Methyl-1,4-diazepan-1-yl)ethyl 4-(4-methylphenyl)piperazine-1-carboxylate

HRID 417986노트

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HRID 417986 반응식
[CH3:1][N:2]1[CH2:8][CH2:7][CH2:6][N:5]([CH2:9][CH2:10][OH:11])[CH2:4][CH2:3]1.CN1CC[O:16][CH2:15]C1.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=O.Cl.Cl.[CH3:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]2[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]2)=[CH:37][CH:36]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[CH3:34][C:35]1[CH:36]=[CH:37][C:38]([N:41]2[CH2:46][CH2:45][N:44]([C:15]([O:11][CH2:10][CH2:9][N:5]3[CH2:6][CH2:7][CH2:8][N:2]([CH3:1])[CH2:3][CH2:4]3)=[O:16])[CH2:43][CH2:42]2)=[CH:39][CH:40]=1

참가 물질

8

반응물 5

HCID 79724-MethylmorpholineHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 831121-(p-Tolyl)piperazine dihydrochlorideHCID 2397252-(4-Methyl-1,4-diazepan-1-yl)ethanol

생성물 1

HCID 426330972-(4-Methyl-1,4-diazepan-1-yl)ethyl 4-(4-methylphenyl)piperazine-1-carboxylate수율 3%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

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.

후처리

  1. waitat room temperature for 2 hours
  2. stirringThe reaction mixture was stirred at room temperature for 3 h
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in EtOAc (300 mL)
  5. washwashed sequentially with 1 M aq Na2CO3 solution (5×200 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by normal phase column chromatography (
  9. washeluting with DCM
  10. additionfollowed by a 85:15 mixture of DCM
  11. dissolutionThe resulting residue was dissolved in DCM (50 mL)
  12. stirringstirred with solid K2CO3 for 20 minutes
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-8b6d08937b4544338ab319452703a2fd
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093248B2

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