Isopropanol → 6-(1H-Indol-4-yl)-4-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole

HRID 1615971Notes

Reaction equation

HRID 1615971 reaction equation
Br[C:2]1[CH:3]=[C:4]([N+:17]([O-:19])=[O:18])[C:5]2[C:9]([CH:10]=1)=[N:8][N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH:6]=2.[NH:20]1[C:28]2[C:23](=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21]1.C(=O)([O-])O.[Na+].C(O)(C)C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(OCC)(=O)C.O>[NH:20]1[C:28]2[C:23](=[C:24]([C:2]3[CH:3]=[C:4]([N+:17]([O-:19])=[O:18])[C:5]4[C:9]([CH:10]=3)=[N:8][N:7]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[CH:6]=4)[CH:25]=[CH:26][CH:27]=2)[CH:22]=[CH:21]1

Participants

8

Reactant 4

HCID 3776IsopropanolHCID 516892Sodium BicarbonateHCID 27631731H-Indole-4-boronic acidHCID 582558186-Bromo-4-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole

Product 1

HCID 582680086-(1H-Indol-4-yl)-4-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazoleYield 310.2%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

Five reactions were set up with 6-bromo-4-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole (500 mg, 1.53 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (125 mg, 0.153 mmol), 1H-indol-4-ylboronic acid (370 mg, 2.3 mmol), saturated aqueous sodium hydrogen carbonate (3 ml) and isopropyl alcohol (12 ml) in each. They were all heated at 150° C. for 10 minutes in the microwave. The reaction mixtures were combined and water (250 ml) and ethyl acetate (250 ml) added. The mixture was filtered and the organic layer collected. The organic layer was washed with water followed by brine. The organic layer was dried over magnesium sulphate, filtered and solvent removed in vacuo. The residue was dissolved in dichloromethane and pre-absorbed onto silica. Purification was carried out using chromatography on silica eluting with 0-25% ethyl acetate in cyclohexane. The desired fractions were collected and combined and solvent removed in vacuo to give the title compound as a yellow solid (1.72 g).

Workup

  1. customThe reaction mixtures
  2. filtrationThe mixture was filtered
  3. customthe organic layer collected
  4. washThe organic layer was washed with water
  5. dry with materialThe organic layer was dried over magnesium sulphate
  6. filtrationfiltered
  7. customsolvent removed in vacuo
  8. dissolutionThe residue was dissolved in dichloromethane
  9. custompre-absorbed onto silica
  10. customPurification
  11. customThe desired fractions were collected
  12. customsolvent removed in vacuo

Sources & evidence

ORD record
ord-ecddbaf0598d4f12a201db0b49060660
Source dataset
uspto-grants-2014_07
Patent number
US08765743B2

Reaction notes

Loading…