Water → 2-methyl-4-[(methyloxy)methyl]-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole

HRID 2088626노트

반응식

HRID 2088626 반응식
[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:17])([F:16])[F:15])[C:9]=2[CH3:18])[C:5]2[CH:19]=[C:20]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)[CH:21]=[C:22]([CH2:23][OH:24])[C:4]=2[N:3]=1.[H-].[Na+].[CH3:33]I.O>CN(C)C=O>[CH3:1][C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([F:15])([F:17])[F:16])[C:9]=2[CH3:18])[C:5]2[CH:19]=[C:20]([N:25]3[CH2:26][CH2:27][O:28][CH2:29][CH2:30]3)[CH:21]=[C:22]([CH2:23][O:24][CH3:33])[C:4]=2[N:3]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 6328Methyl iodide2회HCID 24758Sodium hydride2회HCID 56960404[2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazol-4-yl]methanol

생성물 1

HCID 569609602-methyl-4-[(methyloxy)methyl]-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazole

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To the mixture of [2-methyl-1-{[2-methyl-3-(trifluoromethyl)phenyl]methyl}-6-(4-morpholinyl)-1H-benzimidazol-4-yl]methanol, prepared as described in Example 43 (160 mg, 0.381 mmol) in N,N-Dimethylformamide (DMF) (15 mL), sodium hydride (30.5 mg, 0.763 mmol) was added in and followed by the addition of methyl iodide (0.048 mL, 0.763 mmol). The reaction was stirred at rt for 3 hours. More sodium hydride (30.5 mg, 0.763 mmol) and methyl iodide (0.048 mL, 0.763 mmol) was added in. The reaction was stirred at rt for another 2 hours then Water (70 mL) was added in. The mixture was extracted with EtOAc (100 mL). The organic phase was washed with Brine (100 mL), dried (MgSO4) and concentrated. The crude was subjected to ISCO purification (0˜2% MeOH/DCM) to give the product. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.36 (s, 3H) 2.54 (s, 3H) 3.00-3.07 (m, 4H) 3.37 (s, 3H) 3.68-3.75 (m, 4H) 4.76 (s, 2H) 5.52 (s, 2H) 6.32 (d, J=7.83 Hz, 1H) 6.88 (m, 2H) 7.25 (s, 1H) 7.60 (d, 1H). MS(ES+) m/e 434.4 [M+H]+.

후처리

  1. customprepared
  2. additionwas added in and
  3. stirringThe reaction was stirred at rt for another 2 hours
  4. extractionThe mixture was extracted with EtOAc (100 mL)
  5. washThe organic phase was washed with Brine (100 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customThe crude was subjected to ISCO purification (0˜2% MeOH/DCM)
  9. customto give the product

출처 및 근거

ORD 기록
ord-31f109c44d9c4f8782ee63871309163e
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08435988B2

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