HCID 10915701, compound → HCID 71253571, compound

HRID 1775066Notes

Reaction equation

HRID 1775066 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[N:9][N:8]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[C:5]2=[CH:6][N:7]=1.C([Sn]([C:36]1[C:37](=[O:41])[O:38][CH2:39][CH:40]=1)(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.C1(C)C=CC=CC=1>[C:11]1([C:10]2[C:4]3[C:5](=[CH:6][N:7]=[C:2]([C:40]4[CH2:39][O:38][C:37](=[O:41])[CH:36]=4)[CH:3]=3)[N:8]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[N:9]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 2

HCID 10915701HCID 10915701, compoundHCID 866766845-bromo-3-phenyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

Product 1

HCID 71253571HCID 71253571, compoundYield 32.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

A high-pressure reaction vessel was charged with 5-bromo-3-phenyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (400.0 mg, 1.12 mmol), bis(triphenylphosphine)palladium(II) chloride (79.0 mg, 0.11 mmol), and anhydrous toluene (8.0 mL). Tributylstannanyl-5H-furan-2-one (437.5 mg, 1.17 mmol) was added, and the reaction mixture was vacuum-purged and back filled with nitrogen (3×). The vessel was sealed, and the reaction mixture was stirred at 110° C. for 3 days. The reaction was cooled to RT and slowly poured into saturated aqueous sodium bicarbonate solution (30 mL). The resultant mixture was extracted with ethyl acetate (3×75 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude product was purified using flash column chromatography (Si-PPC gradient elution, solvent: 0-100% ethyl acetate in heptanes) to give 4-(3-phenyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridin-5-yl)furan-2(5H)-one as white solid (130.0 mg, 32.2%). LC/MS: m/z 362.3 [M+1].

Workup

  1. customA high-pressure reaction vessel
  2. customthe reaction mixture was vacuum-purged
  3. additionback filled with nitrogen (3×)
  4. customThe vessel was sealed
  5. temperatureThe reaction was cooled to RT
  6. additionslowly poured into saturated aqueous sodium bicarbonate solution (30 mL)
  7. extractionThe resultant mixture was extracted with ethyl acetate (3×75 mL)
  8. dry with materialThe combined organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe crude product was purified
  12. washflash column chromatography (Si-PPC gradient elution, solvent: 0-100% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-02354a1edcf546908f0baafc4f9b9640
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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