Potassium Phosphate, Tribasic → 3-cyclopropyl-1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-4-nitro-1H-indazole

HRID 79396Notes

Reaction equation

HRID 79396 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]2[CH:19]=[CH:18][N:17]([CH:20]([CH3:22])[CH3:21])[N:16]=2)[N:3]=1.[CH:23]1(B(O)O)[CH2:25][CH2:24]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O>[CH:23]1([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][C:9]=3[N+:11]([O-:13])=[O:12])[N:4]([CH2:14][C:15]3[CH:19]=[CH:18][N:17]([CH:20]([CH3:22])[CH3:21])[N:16]=3)[N:3]=2)[CH2:25][CH2:24]1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 2760897Cyclopropylboronic acidHCID 67259688HCID 67259688, compound

Product 1

HCID 672599083-cyclopropyl-1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-4-nitro-1H-indazoleYield 67.2%

Reagents, catalysts & solvents 1

HCID 22272177Toluene waterSolvent

Conditions

Temperature
105 °C

Procedure

A flask was charged with 3-bromo-1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-4-nitro-1H-indazole (1.8 g, 4.94 mmol), cyclopropylboronic acid (0.849 g, 9.88 mmol), potassium phosphate (3.15 g, 14.8 mmol) and 20:1 toluene/water (10.5 mL). The mixture was degassed for 30 minutes with an argon filled balloon. Palladium acetate was added (55.5 mg, 0.247 mmol) followed by tricyclohexyl phosphine (0.139 g, 0.494 mmol). The mixture was further degassed with argon and heated at 100-110° C. for 16 hours. The mixture was filtered through GF/F paper, rinsing with EtOAc, concentrated under vacuum and the residue was purified by silica gel chromatography (1-20% EtOAc in hexanes) to provide 3-cyclopropyl-1-((1-isopropyl-1H-pyrazol-3-yl)methyl)-4-nitro-1H-indazole (1.08 g, 67% yield) as a yellow solid.

Workup

  1. customThe mixture was degassed for 30 minutes with an argon filled balloon
  2. additionPalladium acetate was added (55.5 mg, 0.247 mmol)
  3. customThe mixture was further degassed with argon
  4. filtrationThe mixture was filtered through GF/F paper
  5. washrinsing with EtOAc
  6. concentrationconcentrated under vacuum
  7. customthe residue was purified by silica gel chromatography (1-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-b5ae243c72ae42b58882345d83a3c85f
Source dataset
uspto-grants-2014_09
Patent number
US08841455B2

Reaction notes

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