N,N,N',N'-Tetramethylethylenediamine → HCID 57612926, compound

HRID 1095367Notes

Reaction equation

HRID 1095367 reaction equation
[C:1]([N:5]1[CH:17]=[C:16]2[C:7]([C:8](=[O:18])[NH:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=32)=[N:6]1)([CH3:4])([CH3:3])[CH3:2].CN(C)CCN(C)C.C([Li])CCC.I[CH2:33][CH2:34][CH:35]1[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH2:36]1>C(OCC)(=O)C.CO.O1CCCC1>[C:1]([N:5]1[C:17]([CH2:33][CH2:34][CH:35]2[CH2:36][CH2:37][N:38]([C:41]([O:43][C:44]([CH3:45])([CH3:47])[CH3:46])=[O:42])[CH2:39][CH2:40]2)=[C:16]2[C:7]([C:8](=[O:18])[NH:9][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=32)=[N:6]1)([CH3:4])([CH3:2])[CH3:3]

Participants

8

Reactant 4

HCID 8037N,N,N',N'-TetramethylethylenediamineHCID 9974426Tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylateHCID 10776486HCID 10776486, compoundHCID 178418339Butyllithium

Product 1

HCID 57612926HCID 57612926, compoundYield 6.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-78 °C

Procedure

To a round-bottomed flask containing 2-tert-butyl-2,5-dihydro-pyrazolo[3,4-c]quinolin-4-one (1.5 g, 6.2 mmol) was added tetrahydrofuran (20 mL) followed by N,N,N′,N′-tetramethylethylenediamine (3.6 g, 31.1 mmol). The reaction was stirred under nitrogen in an ice bath. To this suspension n-butyllithium (2.5 M in hexanes, 7.47 mL, 18.67 mmol) was added dropwise. The reaction mixture was cooled to −78° C. in an acetone-dry ice bath and tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylate (2.3 g, 6.84 mmol) was added to the reaction. The reaction was warmed to ambient temperature over 30 minutes and stirred at that temperature for another 2 hours. Methanol was carefully added to quench the reaction and the solvent was evaporated to afford a dark oil. The oil was taken up in ethyl acetate and the organic layer was washed with aqueous saturated sodium bicarbonate. The organic layer was separated, dried (magnesium sulfate), filtered, and evaporated to afford a dark oil. The product was purified twice by automated flash chromatography (Combiflash Separation System, eluted with a gradient of 0-5% methanol in dichloromethane with 1% ammonium hydroxide) to provide tert-butyl 4-[2-(2-tert-butyl-4-oxo-4,5-dihydro-2H-pyrazolo[3,4-c]quinolin-1-yl)-ethyl]-piperidine-1-carboxylate as a gray solid (0.17 g), mp 223-225° C.; MS (ESI) m/z 453 (M+H).

Workup

  1. temperatureThe reaction was warmed to ambient temperature over 30 minutes
  2. stirringstirred at that temperature for another 2 hours
  3. customto quench
  4. customthe reaction
  5. customthe solvent was evaporated
  6. customto afford a dark oil
  7. washthe organic layer was washed with aqueous saturated sodium bicarbonate
  8. customThe organic layer was separated
  9. dry with materialdried (magnesium sulfate)
  10. filtrationfiltered
  11. customevaporated
  12. customto afford a dark oil
  13. customThe product was purified twice by automated flash chromatography (
  14. customCombiflash Separation System
  15. washeluted with a gradient of 0-5% methanol in dichloromethane with 1% ammonium hydroxide)

Sources & evidence

ORD record
ord-911427c80bf74dcaa984be65bb9c924e
Source dataset
uspto-grants-2012_03
Patent number
US08138173B2

Reaction notes

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