Triethylamine → 8-fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)quinoline

HRID 338997Notes

Reaction equation

HRID 338997 reaction equation
Br[C:2]1[C:11]([F:12])=[C:10]2[C:5]([CH:6]=[CH:7][C:8]([CH3:13])=[N:9]2)=[CH:4][CH:3]=1.[CH3:14][N:15]1[CH:19]=[C:18](B2OC(C)(C)C(C)(C)O2)[CH:17]=[N:16]1.[F-].[Cs+].C(N(CC)CC)C>CC(O)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>[F:12][C:11]1[C:2]([C:18]2[CH:17]=[N:16][N:15]([CH3:14])[CH:19]=2)=[CH:3][CH:4]=[C:5]2[C:10]=1[N:9]=[C:8]([CH3:13])[CH:7]=[CH:6]2

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 25953Cesium fluorideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 709833547-Bromo-8-fluoro-2-methylquinoline

Product 1

HCID 709839848-fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)quinolineYield 87.6%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 7-bromo-8-fluoro-2-methylquinoline (0.15 g, 0.63 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.26 g, 1.25 mmol), PdCl2(dppf)*dcm (0.051 g, 0.063 mmol), CsF (0.247 g, 1.62 mmol) and triethylamine (0.13 mL, 0.94 mmol) in IPA (3 mL) was heated at 100° C. in a sealed tube for 6 hours. After cooling to ambient temperature, water (10 mL) and ethyl acetate (20 mL) were added. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (ethyl acetate) to give 8-fluoro-2-methyl-7-(1-methyl-1H-pyrazol-4-yl)quinoline (0.132 g, 87.6%) as a solid.

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried (sodium sulfate)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-3e951482ec4c49ef8f38cb69c7060fda
Source dataset
uspto-grants-2014_11
Patent number
US08889704B2

Reaction notes

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