Tetrahydrofuran → HCID 57446217, compound

HRID 1095351Notes

Reaction equation

HRID 1095351 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.[O:21]1CCCC1.C([Li])CCC.[O:31]=[CH:32][CH2:33][CH:34]1[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]1>C(#N)C>[OH:31][CH:32]([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:21])[CH2:33][CH:34]1[CH2:35][CH2:36][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:38][CH2:39]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 10353694tert-Butyl 4-(2-oxoethyl)piperidine-1-carboxylateHCID 57454660HCID 57454660, compoundHCID 178418339Butyllithium

Product 1

HCID 57446217HCID 57446217, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

2-Phenyl-2,5-dihydro-4H-pyrazolo[3,4-c]quinoline-one (574 mg, 2.20 mmol) was combined with N,N,N′N′-tetramethylethylenediamine (1.5 mL), and tetrahydrofuran (24 mL) under an atmosphere of nitrogen. The mixture was chilled to 0° C. A solution of n-butyllithium in hexanes (2.0 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 tert-butyl 4-(2-oxoethyl)piperidine-1-carboxylate (1.0 g, 4.4 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 oil. The oil was purified by automated flash chromatography (AnaLogix, eluted with a gradient of 0-30% CMA in chloroform) to provide an oily solid. The oily solid was stirred in acetonitrile and filtered to provide 450 mg of tert-butyl 4-[2-hydroxy-2-(4-oxo-2-phenyl-4,5-dihydro-2H-pyrazolo[3,4-c]quinolin-1-yl)ethyl]piperidine-1-carboxylate as a white solid, mp 253-254° C. MS (APCI) m/z 489 (M+H)+; Anal. calcd for C28H32N4O4: C, 68.83; H, 6.60; N, 11.47. Found: C, 68.49; H, 6.83; N, 11.67.

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 oil
  11. customThe oil was purified by automated flash chromatography (AnaLogix
  12. washeluted with a gradient of 0-30% CMA in chloroform)
  13. customto provide an oily solid
  14. filtrationfiltered

Sources & evidence

ORD record
ord-3bdb34fbdc424935aa8668327f200d3a
Source dataset
uspto-grants-2012_03
Patent number
US08138173B2

Reaction notes

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