Tetrabutylammonium Fluoride → 4-methoxy-3-[(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethynyl]-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine

HRID 1253471Notes

Reaction equation

HRID 1253471 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][N:6]2[CH:11]=[C:10]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)[CH:9]=[C:8]([O:18][CH3:19])[C:7]=12)#[CH:2].I[C:21]1[CH:22]=[N:23][N:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:25]=1[CH3:26].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>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.O1CCCC1>[CH3:19][O:18][C:8]1[C:7]2[N:6]([N:5]=[CH:4][C:3]=2[C:1]#[C:2][C:21]2[CH:22]=[N:23][N:24]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:25]=2[CH3:26])[CH:11]=[C:10]([C:12]2[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=2)[CH:9]=1

Participants

6

Reactant 3

HCID 2724141Tetrabutylammonium FluorideHCID 27764444-Iodo-5-methyl-1-phenyl-1H-pyrazoleHCID 584046903-ethynyl-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine

Product 1

HCID 584046694-methoxy-3-[(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethynyl]-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

3-ethynyl-4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine (30.0 mg, 0.119 mmol), 4-iodo-5-methyl-1-phenyl-1H-pyrazole (67.6 mg, 0.238 mmol), and bis(triphenylphosphine)palladium(II) chloride (8.4 mg, 0.012 mmol) were combined into one vial fitted with a Teflon septum. The vial was flushed with nitrogen and tetra-n-butylammonium fluoride (0.36 mL, 0.36 mmol, 1M in THF) and tetrahydrofuran (0.2 mL) were added. After sparging with nitrogen for 5 minutes, the reaction was heated to 80° C. for one hour. The reaction was cooled to ambient temperature, then diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate. The organic layer was separated, and the aqueous layer was back extracted with ethyl acetate two times. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC reverse phase (C-18), eluting with acetonitrile/water+0.05% TFA. The fractions containing product were combined and diluted in ethyl acetate, then washed with aqueous sodium bicarbonate and dried over sodium sulfate. The solution was filtered and concentrated under reduced pressure to give 4-methoxy-3-[(5-methyl-1-phenyl-1H-pyrazol-4-yl)ethynyl]-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridine

Workup

  1. additionwere added
  2. customAfter sparging with nitrogen for 5 minutes
  3. temperatureThe reaction was cooled to ambient temperature
  4. additiondiluted with ethyl acetate
  5. washwashed with saturated aqueous sodium bicarbonate
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was back extracted with ethyl acetate two times
  8. dry with materialThe combined organic layers were dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by preparative HPLC reverse phase (C-18)
  12. washeluting with acetonitrile/water+0.05% TFA
  13. additionThe fractions containing product
  14. additiondiluted in ethyl acetate
  15. washwashed with aqueous sodium bicarbonate
  16. dry with materialdried over sodium sulfate
  17. filtrationThe solution was filtered
  18. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fe4a9229f23944668219cdc314df689e
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

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