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Sodium Carbonate → 3-(1H-benzo[d]imidazol-2-yl)-5-(3-(methylsulfonyl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1047529
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HRID 1047529 반응식
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16](Br)[CH:17]=2)[N:12]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[N:11]=1.[CH3:26][S:27]([C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[CH:34][CH:35]=1)(=[O:29])=[O:28].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:34]3[CH:33]=[CH:32][CH:31]=[C:30]([S:27]([CH3:26])(=[O:29])=[O:28])[CH:35]=3)[CH:17]=2)[N:12]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[N:11]=1
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반응물 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27735423-(Methylsulfonyl)phenylboronic acidHCID 1363522433-(1H-benzo[d]imidazol-2-yl)-5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

생성물 1

HCID 1363522463-(1H-benzo[d]imidazol-2-yl)-5-(3-(methylsulfonyl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole수율 22.6%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 8028Tetrahydrofuran용매

실험 절차

3-(1H-Benzo[d]imidazol-2-yl)-5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (30 mg, 0.0755 mmol), 3-(methylsulfonyl)phenyl boronic acid (15 mg, 0.075 mmol) and triphenylphosphine (2 mg, 0.007 mmol) were dissolved in a mixture of THF (6 mL), and 1M sodium carbonate (8 mg, 0.075 mmol) and palladium (II) acetate (2 mg, 0.009 mmol) were added. The solution was heated overnight at reflux. After cooling to room temperature, the solvent was removed in vacuo, the residue was dissolved in ethyl acetate (20 mL), and washed with water (10 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (20 mL). The combined organic layers were washed with brine (25 mL), dried over Na2SO4, and concentrated. Purification by flash chromatography (20% ethyl acetate/hexane) afforded the title compound (8 mg) as a white solid. 1H NMR (400 MHz, CDCl3): δ 9.93 (s, 1H), 8.83 (s, 1H), 8.19 (s, 1H), 7.97 (d, 1H, J=8.0 Hz), 7.86 (m, 2H), 7.61 (t, 1H, J=7.6 Hz), 7.45 (m, 1H), 7.24 (m, 4H), 5.77 (dd, 1H, J=2.4 and 9.6 Hz), 4.04 (m, 1H), 3.75 (m, 1H), 3.07 (s, 3H), 2.59 (m, 1H), 2.12 (m, 2H), 1.76 (m, 3H); ESI-MS [M+H]+: 473.3.

후처리

  1. additionwere added
  2. temperatureThe solution was heated overnight
  3. temperatureat reflux
  4. customthe solvent was removed in vacuo
  5. dissolutionthe residue was dissolved in ethyl acetate (20 mL)
  6. washwashed with water (10 mL)
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with ethyl acetate (20 mL)
  9. washThe combined organic layers were washed with brine (25 mL)
  10. dry with materialdried over Na2SO4
  11. concentrationconcentrated
  12. customPurification by flash chromatography (20% ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-1fa1c05261344330ad3aa00b4a6e482b
출처 데이터셋
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08569511B2

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