Tetrahydrofuran → Methyl 3-[2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl]benzoate

HRID 1190859Notes

Reaction equation

HRID 1190859 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[CH:10]=[C:4]2[CH:3]=1.[CH3:18][O:19][C:20]([C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1)=[O:21].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCCC1>C(OCC)(=O)C.ClCCl.O.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]>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[CH:10]=[C:4]3[CH:3]=[C:2]([C:26]4[CH:27]=[C:22]([CH:23]=[CH:24][CH:25]=4)[C:20]([O:19][CH3:18])=[O:21])[CH:7]=[CH:6][N:5]3[N:8]=2)=[CH:12][CH:13]=1

Participants

9

Reactant 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 27347143-(Methoxycarbonyl)benzeneboronic acidHCID 67255182HCID 67255182, compound

Product 1

HCID 53241232Methyl 3-[2-(4-fluorophenyl)pyrazolo[1,5-a]pyridin-5-yl]benzoateYield 71.7%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Under a stream of nitrogen, 0.400 g (1.37 mmol) of 5-bromo-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine obtained in step 5.3, 0.300 g (1.67 mmol) of 3-methoxycarbonylphenylboronic acid and 1.330 g (4.08 mmol) of caesium carbonate are placed in 5 mL of a 9/1 mixture of tetrahydrofuran and water. 0.11 g (0.13 mmol) of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) is added and the medium is heated at 70° C. for 4 hours. The medium is then cooled to room temperature and diluted with 40 mL of dichloromethane and 40 mL of water. The medium is then filtered on a hydrophobic cartridge (Radleys® 70 mL liquid/liquid extraction column) and the organic phase is recovered and concentrated under reduced pressure after addition of 2 g of silica. The residue is purified by chromatography on silica gel, eluting with a mixture of cyclohexane and ethyl acetate (9/1). 0.340 g (71%) of expected product is obtained in the form of a white powder.

Workup

  1. temperatureThe medium is then cooled to room temperature
  2. filtrationThe medium is then filtered on a hydrophobic cartridge (Radleys® 70 mL liquid/liquid extraction column)
  3. customthe organic phase is recovered
  4. concentrationconcentrated under reduced pressure
  5. additionafter addition of 2 g of silica
  6. customThe residue is purified by chromatography on silica gel
  7. washeluting with a mixture of cyclohexane and ethyl acetate (9/1)

Sources & evidence

ORD record
ord-5cc145b3ce444ad88eef436efef8c8d1
Source dataset
uspto-grants-2014_03
Patent number
US08680096B2

Reaction notes

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