Tetrahydrofuran → HCID 57446225, compound

HRID 1095359Notes

Reaction equation

HRID 1095359 reaction equation
[C:1]1([N:7]2[C:19](=O)[C:18]3[C:17]4[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=4[NH:11][CH2:10][C:9]=3[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:21]([Li])[CH2:22][CH2:23][CH3:24].ICCCC.[O:31]1CCCC1>>[CH2:21]([C:19]1[N:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[N:8]=[C:9]2[C:18]=1[C:17]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[NH:11][C:10]2=[O:31])[CH2:22][CH2:23][CH3:24]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 10962Butyl iodideHCID 57454660HCID 57454660, compoundHCID 178418339Butyllithium

Product 1

HCID 57446225HCID 57446225, compound

Conditions

Temperature
0 °C

Procedure

Under a nitrogen atmosphere, a mixture of 2-phenyl-2,5-dihydro-4H-pyrazolo[3,4-c]quinoline-one (3.0 g, 11.5 mmol), N,N,N′N′-tetramethylethylenediamine (7.7 mL), and tetrahydrofuran (128 mL) was chilled to 0° C. A solution of n-butyllithium in hexanes (12 mL of 2.86 M) was added dropwise. After the addition was complete the reaction mixture was stirred for 5 minutes at 0° C. and then cooled to −78° C. To the cooled solution was added iodobutane (3.9 mL, 34.5 mmol). The reaction mixture was warmed to ambient temperature and stirred for 30 minutes before quenching with saturated aqueous ammonium chloride. The aqueous layer was extracted with dichloromethane. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure to 100 mL of solvent. This was placed directly on a silica gel column and purified by automated flash chromatography (AnaLogix, eluted with a gradient of 0-50% CMA in chloroform) to provide 3.7 g of 1-butyl-2-phenyl-2,5-dihydro-4H-pyrazolo[3,4-c]quinolin-4-one as a 2:1 mixture of product to starting material.

Workup

  1. additionAfter the addition
  2. temperaturecooled to −78° C
  3. temperatureThe reaction mixture was warmed to ambient temperature
  4. stirringstirred for 30 minutes
  5. custombefore quenching with saturated aqueous ammonium chloride
  6. extractionThe aqueous layer was extracted with dichloromethane
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure to 100 mL of solvent
  10. custompurified by automated flash chromatography (AnaLogix
  11. washeluted with a gradient of 0-50% CMA in chloroform)

Sources & evidence

ORD record
ord-7e47d95f912147e186ac270a7af3ed3c
Source dataset
uspto-grants-2012_03
Patent number
US08138173B2

Reaction notes

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