O-Phenylenediamine → 3-(1H-benzo[d]imidazol-2-yl)-5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole

HRID 1047525Notes

Reaction equation

HRID 1047525 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[C:5]2[CH:17]=O.[C:19]1([NH2:26])[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[NH2:25].S(=O)(O)[O-].[Na+]>C1COCC1.Cl.C(OCC)(=O)C>[NH:25]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N:26]=[C:17]1[C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([Br:1])[CH:3]=2)[N:7]([CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[N:6]=1

Participants

7

Reactant 3

HCID 7243O-PhenylenediamineHCID 23665763Sodium BisulfiteHCID 866624125-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde

Product 1

HCID 1363522433-(1H-benzo[d]imidazol-2-yl)-5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazoleYield 60%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carbaldehyde (100 mg, 0.323 mmol) and o-phenylene diamine (38.5 mg, 0.356 mmol) were dissolved in dry THF (6 mL), and 2N HCl (2 drops) were added. The solution was heated at a gentle reflux for 30 min, and then 1N sodium bisulfite (2 mL) was added. After overnight at reflux, the solution was cooled to room temperature, and diluted with ethyl acetate (100 mL). The mixture was washed with water and brine, dried over Na2SO4, and concentrated. Purification by flash chromatography (20% ethyl acetate/hexane) afforded the title compound as a pale yellow solid in a 60% yield. 1H NMR (400 MHz, CDCl3): δ 9.86 (s, 1H), 8.79 (d, 1H, J=1.2 Hz), 7.83 (m, 1H), 7.50-7.41 (m, 3H), 7.25-7.22 (m, 2H), 5.69 (dd, 1H, J=2.8 and 8.8 Hz), 3.98 (m, 1H), 3.80 (m, 1H), 2.53 (m, 1H), 2.19 (m, 2H), 1.76 (m, 3H).

Workup

  1. temperatureThe solution was heated at
  2. temperaturea gentle reflux for 30 min
  3. temperatureAfter overnight at reflux
  4. washThe mixture was washed with water and brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customPurification by flash chromatography (20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-d6fd615c17c94a5db2ac331febe48088
Source dataset
uspto-grants-2013_10
Patent number
US08569511B2

Reaction notes

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