Potassium Phosphate, Tribasic → 1-benzyl-3-cyclopropyl-4-nitro-1H-indazole

HRID 79263Notes

Reaction equation

HRID 79263 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[C:12]([N+:17]([O-:19])=[O:18])[CH:13]=[CH:14][CH:15]=2)[C:10](Br)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:21]1(B(O)O)[CH2:23][CH2:22]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C1(C)C=CC=CC=1>[CH2:1]([N:8]1[C:16]2[C:11](=[C:12]([N+:17]([O-:19])=[O:18])[CH:13]=[CH:14][CH:15]=2)[C:10]([CH:21]2[CH2:23][CH2:22]2)=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 67261440HCID 67261440, compound

Product 1

HCID 672600391-benzyl-3-cyclopropyl-4-nitro-1H-indazoleYield 68.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a reaction vial was added 1-benzyl-3-bromo-4-nitro-1H-indazole (100 mg, 0.301 mmol), cyclopropylboronic acid (33.6 mg, 0.391 mmol) and potassium phosphate (192 mg, 0.903 mmol). Toluene (1.5 mL) and water (0.1 mL) were added. The mixture was purged with argon for 30 minutes. Palladium (II) acetate (3.38 mg, 0.0151 mmol) and tri-cyclohexyl phosphine (8.44 mg, 0.0301 mmol) were added. The reaction vessel was purged with argon and sealed. The mixture was heated at 100° C. for 24 hours. The mixture was filtered through glass fiber filter paper, washing with ethyl acetate and methanol followed by concentration under reduced pressure. The material was purified by preparative chromatography on silica, eluting with hexane/ethyl acetate (5:1). The band containing the desired product was isolated and concentrated under reduced pressure to give 1-benzyl-3-cyclopropyl-4-nitro-1H-indazole (60.5 mg).

Workup

  1. customThe mixture was purged with argon for 30 minutes
  2. customThe reaction vessel was purged with argon
  3. customsealed
  4. filtrationThe mixture was filtered through glass fiber
  5. filtrationfilter paper
  6. washwashing with ethyl acetate and methanol
  7. concentrationfollowed by concentration under reduced pressure
  8. customThe material was purified by preparative chromatography on silica
  9. washeluting with hexane/ethyl acetate (5:1)
  10. additionThe band containing the desired product
  11. customwas isolated
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-50a3a9c0ac97412c823cb26c28565544
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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