Sodium Carbonate → 2-(4-Fluorophenyl)-3-(2-fluoro-4-pyridinyl)-pyrazolo[1,5-a]pyridine

HRID 1374706Notes

Reaction equation

HRID 1374706 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]=[CH:21][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:17][C:14]1[CH:15]=[CH:16][C:11]([C:3]2[C:2]([C:23]3[CH:22]=[CH:21][N:20]=[C:19]([F:18])[CH:24]=3)=[C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][N:5]3[N:4]=2)=[CH:12][CH:13]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 219486782-(4-Fluorophenyl)-3-bromopyrazolo[1,5-a]pyridine

Product 1

HCID 99443962-(4-Fluorophenyl)-3-(2-fluoro-4-pyridinyl)-pyrazolo[1,5-a]pyridineYield 27.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of 3-bromo-2-(4-fluorophenyl)-pyrazolo[1,5-a]pyridine (Example le. 1.30 g, 4.5 mmol), 2-fluoro-4-pyridinylboronic acid (Example 46a. 694 mg, 4.9 mmol) and dichlorobis(triphenylphosphine)palladium (316 mg, 0.45 mmol) in DMF (100 mL) was placed in a pre-heated oil bath at 110° C. To the reaction was added, in a dropwise manner, 2M aqueous sodium carbonate (4.5 mL, 9.0 mmol). The reaction was allowed to stir for 2 h and then cooled to room temperature and filtered through a pad of Celite. The Celite pad was washed with ethyl acetate and the filtrate was concentrated to dryness at 50° C. under vacuum. The residue was partitioned between ethyl acetate and water. The layers were separated and the organic phase was 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 (378 mg, 1.23 mmol, 27%). 1H NMR (CDCl3) δ 8.57 (d, 1H, J=6.9 Hz), 8.22(d, 1H, J=5.4 Hz), 7.7(d, 1H, J=9.0 Hz), 7.75(m, 2H), 7.33(m, 1H), 7.14(m, 3H), 6.95(m, 2H). MS (ES+ve) 308 (100, M+).

Workup

  1. customwas placed in a pre-heated oil bath at 110° C
  2. filtrationfiltered through a pad of Celite
  3. washThe Celite pad was washed with ethyl acetate
  4. concentrationthe filtrate was concentrated to dryness at 50° C. under vacuum
  5. customThe residue was partitioned between ethyl acetate and water
  6. customThe layers were separated
  7. dry with materialthe organic phase was dried (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-0962e9678ebd4170839420f22811aef5
Source dataset
uspto-grants-2007_01
Patent number
US07166597B2

Reaction notes

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