Isopropanol → 4-Nitro-2-(tetrahydro-2H-pyran-2-yl)-6-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-2H-indazole

HRID 1695710Notes

Reaction equation

HRID 1695710 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.[O:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH:21]1[O:26][C:27]1[CH:32]=[CH:31][C:30](B(O)O)=[CH:29][CH:28]=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>[N+:17]([C:4]1[C:5]2[C:9]([CH:10]=[C:2]([C:30]3[CH:31]=[CH:32][C:27]([O:26][CH:21]4[CH2:22][CH2:23][CH2:24][CH2:25][O:20]4)=[CH:28][CH:29]=3)[CH:3]=1)=[N:8][N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[CH:6]=2)([O-:19])=[O:18]

Participants

8

Reactant 4

HCID 3776IsopropanolHCID 516892Sodium BicarbonateHCID 50176524-(Tetrahydro-2H-pyran-2-yloxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 582558186-Bromo-4-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole

Product 1

HCID 582557524-Nitro-2-(tetrahydro-2H-pyran-2-yl)-6-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-2H-indazole

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

6-Bromo-4-nitro-2-(tetrahydro-2H-pyran-2-yl)-2H-indazole (500 mg, 1.53 mmol), Pd(dppf)Cl2 (125 mg, 0.153 mmol), [4-(tetrahydro-2H-pyran-2-yloxy)phenyl]boronic acid (511 mg, 2.3 mmol), saturated sodium hydrogen carbonate (aq) (3 ml) and isopropyl alcohol (12 ml) were added to each of 5 microwave vessels. All 5 reactions were heated at 150° C. for 10 mins in a Biotage microwave. The reaction mixtures were combined and water (250 ml) and ethyl acetate (250 ml) were added. The mixture was filtered and the organic layer collected. The organic layer was washed with water, then brine, dried over magnesium sulphate, filtered and dried in vacuo. The residue was purified using silica gel chromatography, eluting with 0-25% ethyl acetate in cyclohexane. Appropriate fractions were combined and the solvent was removed in vacuo to give the title compound, 2.3 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 materialbrine, dried over magnesium sulphate
  6. filtrationfiltered
  7. customdried in vacuo
  8. customThe residue was purified
  9. washeluting with 0-25% ethyl acetate in cyclohexane
  10. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-82f853ec8b684f54ae40b0fe86210e08
Source dataset
uspto-grants-2012_04
Patent number
US08163743B2

Reaction notes

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