Sodium Carbonate → 2-(4-(3-(1H-benzo[d]imidazol-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)phenyl)-2-methylpropanenitrile

HRID 1047535ノート

反応式

HRID 1047535 の反応式
[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.[C:26]([C:28]([C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[CH:33][CH:32]=1)([CH3:30])[CH3:29])#[N:27].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:35]=[CH:36][C:31]([C:28]([CH3:30])([CH3:29])[C:26]#[N:27])=[CH:32][CH:33]=3)[CH:17]=2)[N:12]([CH:20]2[CH2:25][CH2:24][CH2:23][CH2:22][O:21]2)[N:11]=1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 441193244-(2-Cyanoprop-2-yl)benzeneboronic acidHCID 1363522433-(1H-benzo[d]imidazol-2-yl)-5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

生成物 1

HCID 1363522492-(4-(3-(1H-benzo[d]imidazol-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)phenyl)-2-methylpropanenitrile収率 30.3%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 8028Tetrahydrofuran溶媒

実験手順

3-(1H-Benzo[d]imidazol-2-yl)-5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (20 mg, 0.050 mmol), [4-(1cyano-1-methylethyl)phenyl]boronic acid (10 mg, 0.074053 mmol) and triphenylphosphine (2 mg, 0.007 mmol) were dissolved in a mixture of THF (6 mL) and 1M Na2CO3 (aq) (10 mg, 0.094 mmol). Palladium acetate (1 mg, 0.004 mmol) was added and the solution was heated overnight at reflux. After cooling to room temperature, and the solvent was removed in vacuo. The residue was dissolved in ethyl acetate (25 mL) and washed with water (20 mL). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (25 mL). The combined organic layers were washed with brine (20 mL), dried over Na2SO4, and concentrated. Purification by flash chromatography (20% ethyl acetate/hexane) afforded the title compound (7 mg). 1H NMR (400 MHz, CDCl3): δ 8.79 (s, 1H), 7.80 (bs, 1H), 7.75 (m, 2H), 7.70 (m, 1H), 7.64 (m, 1H), 7.53-7.48 (m, 3H), 7.25-7.22 (m, 2H), 5.76 (d, 1H, J=8.4 Hz), 4.06 (m, 1H), 3.77 (m, 1H), 2.55 (m, 1H), 2.10 (m, 2H), 1.73 (m, 3H), 1.72 (s, 6H).

後処理

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

出典と根拠

ORDレコード
ord-fb10d2492f824c1282d92fabf1a8236b
出典データセット
uspto-grants-2013_10
特許番号
US08569511B2

反応ノート

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