Tetrahydrofuran → HCID 57446219, compound

HRID 1095353Notes

Reaction equation

HRID 1095353 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.CN(C)CCN(C)C.C([Li])CCC.[CH:34]1([CH2:40][CH:41]=[O:42])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1.[O:43]1CCCC1>C(#N)C>[CH:34]1([CH2:40][CH:41]([C:19]2[N:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[N:8]=[C:9]3[C:18]=2[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[NH:11][C:10]3=[O:43])[OH:42])[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 3166272-CyclohexylacetaldehydeHCID 57454660HCID 57454660, compoundHCID 178418339Butyllithium

Product 1

HCID 57446219HCID 57446219, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

2-Phenyl-2,5-dihydro-4H-pyrazolo[3,4-c]quinoline-one (4.7 g, 17.9 mmol) was combined with N,N,N′,N′-tetramethylethylenediamine (12 mL), and tetrahydrofuran (200 mL) under an atmosphere of nitrogen. The mixture was chilled to 0° C. A solution of n-butyllithium in hexanes (19 mL of 2.5 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 cyclohexylacetaldehyde (12 g, 35 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 chloroform. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure to afford a yellow oily solid. The oily solid was purified by automated flash chromatography (AnaLogix, eluted with a gradient of 0-30% CMA in chloroform) to provide a yellow solid. The solid was boiled in acetonitrile and filtered. The filtrate was adsorbed onto silica gel and purified by automated flash chromatography (AnaLogix, eluted with a gradient of 0-20% CMA in chloroform) to provide a white foam. The foam was stirred in acetonitrile and filtered to provide 213 mg of 1-(2-cyclohexyl-1-hydroxyethyl)-2-phenyl-2,5-dihydro-4H-pyrazolo[3,4-c]quinolin-4-one as a white powder, mp 254-259° C. MS (APCI) m/z 388 (M+H)+; Anal. calcd for C24H25N3O2: C, 74.39; H, 6.50; N, 10.84. Found: C, 74.40; H, 6.37; N, 10.89.

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 chloroform
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto afford a yellow oily solid
  11. customThe oily solid was purified by automated flash chromatography (AnaLogix
  12. washeluted with a gradient of 0-30% CMA in chloroform)
  13. customto provide a yellow solid
  14. filtrationfiltered
  15. custompurified by automated flash chromatography (AnaLogix
  16. washeluted with a gradient of 0-20% CMA in chloroform)
  17. customto provide a white foam
  18. filtrationfiltered

Sources & evidence

ORD record
ord-7ae98ee972e54c718ad9df1ea5cfa37b
Source dataset
uspto-grants-2012_03
Patent number
US08138173B2

Reaction notes

Loading…