Cesium carbonate → 2-Chloro-4-[1-(tetrahydro-pyran-2-yl)-1H-pyrazol-4-yl]-pyridine

HRID 241684Notes

Reaction equation

HRID 241684 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([CH:7]2[CH2:12][CH2:11][CH2:10][CH2:9][O:8]2)[CH:6]=1.[Cl:13][C:14]1[CH:19]=[C:18](B(O)O)[CH:17]=[CH:16][N:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(Cl)Cl.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:13][C:14]1[CH:19]=[C:18]([C:2]2[CH:3]=[N:4][N:5]([CH:7]3[CH2:12][CH2:11][CH2:10][CH2:9][O:8]3)[CH:6]=2)[CH:17]=[CH:16][N:15]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 51515952-Chloropyridine-4-boronic acidHCID 467394664-bromo-1-(oxan-2-yl)-1H-pyrazole

Product 1

HCID 595343552-Chloro-4-[1-(tetrahydro-pyran-2-yl)-1H-pyrazol-4-yl]-pyridineYield 43%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

4-Bromo-1-(tetrahydro-pyran-2-yl)-1H-pyrazole (0.73 g) and 2-chloropyridine-4-boronic acid (0.20 g) were dissolved in dry DMF (2 mL) under inert atmosphere and 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium(II) (102 mg) was added followed by caesium carbonate (0.84 g). The mixture was heated to 80° C. and stirred for 2 h. After cooling to room temperature the reaction mixture was diluted with DCM and the inorganic salts filtered off. The filtrate was washed with water and brine, dried under Na2SO4, filtered and the solvent was evaporated under reduced pressure. The crude was purified by flash chromatography (20 g Isolute® silica gel cartridge; gradient elution: hexane/EtOAc from 10/0 to 8.5/1.5) affording the title compound (144 mg). UPLC (Rt)=1.39 min (method M)

Workup

  1. additionwas added
  2. temperatureAfter cooling to room temperature the reaction mixture
  3. filtrationthe inorganic salts filtered off
  4. washThe filtrate was washed with water and brine
  5. customdried under Na2SO4
  6. filtrationfiltered
  7. customthe solvent was evaporated under reduced pressure
  8. customThe crude was purified by flash chromatography (20 g Isolute® silica gel cartridge; gradient elution: hexane/EtOAc from 10/0 to 8.5/1.5)

Sources & evidence

ORD record
ord-aa0e4954889245dc8d93035fa29dd614
Source dataset
uspto-grants-2014_02
Patent number
US08653075B2

Reaction notes

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