Sodium Carbonate → 4-phenyl-6-(trifluoromethyl)-1H-indazole

HRID 58069

Reaction equation

HRID 58069 reaction equation
Br[C:2]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][NH:6]2.[C:15]1(B(O)O)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[C:24](=[O:27])([O-])[O-:25].[Na+].[Na+]>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].O1CCOCC1>[C:24]([OH:25])([C:11]([F:14])([F:13])[F:12])=[O:27].[C:15]1([C:2]2[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[C:7]3[C:3]=2[CH:4]=[N:5][NH:6]3)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 247292324-Bromo-6-(trifluoromethyl)-1H-indazole

Product 2

HCID 6422Trifluoroacetic acidHCID 717352054-phenyl-6-(trifluoromethyl)-1H-indazoleYield 70.8%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A vessel was charged with 4-bromo-6-(trifluoromethyl)-1H-indazole (0.1 g, 0.377 mmol), phenylboronic acid (0.069 g, 0.566 mmol), PdCl2(dppf) (0.014 g, 0.019 mmol), and dioxane (3 mL). To the resulting slurry was added 2N aqueous sodium carbonate (0.377 mL, 0.755 mmol). The mixture was purged with nitrogen, heated in a microwave reactor at 120° C. for 30 minutes, and then filtered through a pad of Celite, which was rinsed with methanol. The solvent was removed in vacuo, and the resulting residue was taken up in DMSO and methanol (1:1) and was purified via acidic preparative HPLC (Waters SunFire C18, 5 μm, 30 mm ID×75 mm column), eluting with a gradient of 55-80% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA). The collected fractions were dried in vacuo to give a TFA salt of the title compound as a tan solid (35 mg, 35%). 1H NMR (400 MHz, CDCl3) δ ppm 7.43-7.62 (m, 4H), 7.71 (d, J=7.07 Hz, 2H), 7.83 (s, 1H), 8.23-8.38 (m, 1H), 8.47 (br s, 1H); ESI-MS m/z [M+H]+ calc'd for C14H9F3N2, 263.1. found 263.1.

Workup

  1. customThe mixture was purged with nitrogen
  2. filtrationfiltered through a pad of Celite, which
  3. washwas rinsed with methanol
  4. customThe solvent was removed in vacuo
  5. custommethanol (1:1) and was purified via acidic preparative HPLC (Waters SunFire C18, 5 μm, 30 mm ID×75 mm column)
  6. washeluting with a gradient of 55-80% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA)
  7. customThe collected fractions were dried in vacuo

Sources & evidence

ORD record
ord-707602f09c814b598495f3146da421bc
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Linked notes

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