4-Bromo-6-(trifluoromethyl)-1H-indazole → 4-(6-chloro-2-methylpyridin-3-yl)-6-(trifluoromethyl)-1H-indazole

HRID 58111Notes

Reaction equation

HRID 58111 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.[Cl:15][C:16]1[N:21]=[C:20]([CH3:22])[C:19](B(O)O)=[CH:18][CH:17]=1>O1CCOCC1.C([O-])(O)=O.[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]>[Cl:15][C:16]1[N:21]=[C:20]([CH3:22])[C:19]([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:18][CH:17]=1

Participants

6

Reactant 2

HCID 247292324-Bromo-6-(trifluoromethyl)-1H-indazoleHCID 441191526-Chloro-2-methylpyridine-3-boronic acid

Product 1

HCID 897832784-(6-chloro-2-methylpyridin-3-yl)-6-(trifluoromethyl)-1H-indazoleYield 605.6%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
140 °C

Procedure

The reaction was carried out in eight microwave vials. To each vial were added 4-bromo-6-(trifluoromethyl)-1H-indazole (0.5 g, 1.886 mmol), (6-chloro-2-methylpyridin-3-yl)boronic acid (0.3875 g, 2.264 mmol) and PdCl2(dppf) (0.069 g, 0.0944 mmol) in dioxane (12 mL) and aqueous saturated NaHCO3 (3 mL). The resulting light-brown suspensions were each heated at 140° C. for 60 minutes in a microwave reactor. The reaction mixtures were combined and concentrated and the crude residue was diluted with EtOAc and washed with water. The volatiles were removed via rotary evaporation and the product purified by CombiFlash® chromatography, eluting with a gradient of 0-100% EtOAc in heptane over a period of 180 minutes. The product-containing fractions were combined and the volatiles removed via rotary evaporation to give the title compound (3.56 g, 76%). ESI-MS m/z [M+H]+ calc'd for C14H9ClF3N3, 312.05. found 311.89.

Workup

  1. customThe reaction mixtures
  2. concentrationconcentrated
  3. additionthe crude residue was diluted with EtOAc
  4. washwashed with water
  5. customThe volatiles were removed via rotary evaporation
  6. customthe product purified by CombiFlash® chromatography
  7. washeluting with a gradient of 0-100% EtOAc in heptane over a period of 180 minutes
  8. customthe volatiles removed via rotary evaporation

Sources & evidence

ORD record
ord-b2a6bf0f8af745aba8c4ecd316b99fbf
Source dataset
uspto-grants-2016_09
Patent number
US09434743B2

Reaction notes

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