Tetrahydrofuran → tert-butyl 4-[2-(4-oxo-2-phenyl-4,5-dihydro-2H-pyrazolo[3,4-c]quinolin-1-yl)ethyl]piperidine-1-carboxylate

HRID 1095349Notes

Reaction equation

HRID 1095349 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.I[CH2:35][CH2:36][CH:37]1[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]1.[O:50]1CCCC1>C(#N)C>[O:50]=[C:10]1[C:9]2=[N:8][N:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[C:19]([CH2:35][CH2:36][CH:37]3[CH2:42][CH2:41][N:40]([C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH2:39][CH2:38]3)=[C:18]2[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[NH:11]1

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 9974426Tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylateHCID 57454660HCID 57454660, compoundHCID 178418339Butyllithium

Product 1

HCID 57446216tert-butyl 4-[2-(4-oxo-2-phenyl-4,5-dihydro-2H-pyrazolo[3,4-c]quinolin-1-yl)ethyl]piperidine-1-carboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

Under a nitrogen atmosphere, a mixture of 2-phenyl-2,5-dihydro-4H-pyrazolo[3,4-c]quinoline-one (1.76 g, 6.76 mmol), N,N,N′,N′-tetramethylethylenediamine (4.5 mL), and tetrahydrofuran (75 mL) was chilled to 0° C. A solution of n-butyllithium in hexanes (8.1 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-iodoethyl)piperidine-1-carboxylate (3.0 g, 8.8 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 yellow oil was stirred in acetonitrile and filtered to provide 1.4 g (75% pure) of tert-butyl 4-[2-(4-oxo-2-phenyl-4,5-dihydro-2H-pyrazolo[3,4-c]quinolin-1-yl)ethyl]piperidine-1-carboxylate as a tan solid.

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. filtrationfiltered

Sources & evidence

ORD record
ord-6a1d59d683cb452faa1c5bda4123acdc
Source dataset
uspto-grants-2012_03
Patent number
US08138173B2

Reaction notes

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