Sodium Carbonate → 3-(2,6-Difluoro-4-pyridinyl)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine

HRID 1374708Notes

Reaction equation

HRID 1374708 reaction equation
Br[C:2]1[C:3]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[N:4][N:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=12.[F:18][C:19]1[CH:24]=[C:23](B(O)O)[CH:22]=[C:21]([F:28])[N:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:18][C:19]1[CH:24]=[C:23]([C:2]2[C:3]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)=[N:4][N:5]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=23)[CH:22]=[C:21]([F:28])[N:20]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27627472,6-Difluoropyridine-4-boronic acidHCID 219486782-(4-Fluorophenyl)-3-bromopyrazolo[1,5-a]pyridine

Product 1

HCID 98584533-(2,6-Difluoro-4-pyridinyl)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridineYield 25.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-bromo-2-(4-fluorophenyl)-pyrazolo[1,5-a]pyridine (from Example le, 570 mg, 1.96 mmol), 2,6-difluoro-4-pyridyl-boronic acid (340 mg, 2.15 mmol) and dichlorobis(triphenylphosphine)palladium (137 mg, 0.196 mmol) in DMF (10.0 mL) was placed in a pre-heated oil bath at 110° C. To the reaction was added, in a dropwise manner, 2M sodium carbonate (2.00 mL, 4.00 mmol). The reaction was allowed to stir for 45 min before cooling to room temperature and filtering through a Celite 545 pad. The Celite filter was washed with ethyl acetate and the filtrate was concentrated to dryness at 50° C. under vacuum. The residue was dissolved in methylene chloride and dried (MgSO4). The drying agent was removed by filtration and the filtrate was concentrated and purified by silica gel chromatography to yield the title compound (160 mg, 0.492 mmol, 25%). 1H NMR (CDCl3) δ 8.53(d, 1H, J=6.8 Hz), 7.67(d, 1H, J=8.8 Hz), 7.53(dd, 2H, J=5.6, 8.0 Hz), 7.31(t, 1H, J=7.6 Hz), 7.11(t, 2H, J=8.4 Hz), 6.93(t, 1H, J=6.8 Hz), 6.75(s, 2H). MS (ES+ve): 326 (90, M+).

Workup

  1. customwas placed in a pre-heated oil bath at 110° C
  2. filtrationfiltering through a Celite 545 pad
  3. filtrationThe Celite filter
  4. washwas washed with ethyl acetate
  5. concentrationthe filtrate was concentrated to dryness at 50° C. under vacuum
  6. dissolutionThe residue was dissolved in methylene chloride
  7. dry with materialdried (MgSO4)
  8. customThe drying agent was removed by filtration
  9. concentrationthe filtrate was concentrated
  10. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-96215039734a4d5694ec23d25c02db3a
Source dataset
uspto-grants-2007_01
Patent number
US07166597B2

Reaction notes

Loading…